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Verdugo-Avello F, Wychowaniec JK, Villacis-Aguirre CA, D'Este M, Toledo JR. Bone microphysiological models for biomedical research. LAB ON A CHIP 2025; 25:806-836. [PMID: 39906932 DOI: 10.1039/d4lc00762j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2025]
Abstract
Bone related disorders are highly prevalent, and many of these pathologies still do not have curative and definitive treatment methods. This is due to a complex interplay of multiple factors, such as the crosstalk between different tissues and cellular components, all of which are affected by microenvironmental factors. Moreover, these bone pathologies are specific, and current treatment results vary from patient to patient owing to their intrinsic biological variability. Current approaches in drug development to deliver new drug candidates against common bone disorders, such as standard two-dimensional (2D) cell culture and animal-based studies, are now being replaced by more relevant diseases modelling, such as three-dimension (3D) cell culture and primary cells under human-focused microphysiological systems (MPS) that can resemble human physiology by mimicking 3D tissue organization and cell microenvironmental cues. In this review, various technological advancements for in vitro bone modeling are discussed, highlighting the progress in biomaterials used as extracellular matrices, stem cell biology, and primary cell culture techniques. With emphasis on examples of modeling healthy and disease-associated bone tissues, this tutorial review aims to survey current approaches of up-to-date bone-on-chips through MPS technology, with special emphasis on the scaffold and chip capabilities for mimicking the bone extracellular matrix as this is the key environment generated for cell crosstalk and interaction. The relevant bone models are studied with critical analysis of the methods employed, aiming to serve as a tool for designing new and translational approaches. Additionally, the features reported in these state-of-the-art studies will be useful for modeling bone pathophysiology, guiding future improvements in personalized bone models that can accelerate drug discovery and clinical translation.
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Affiliation(s)
- Francisco Verdugo-Avello
- Biotechnology and Biopharmaceuticals Laboratory, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Víctor Lamas 1290, P.O. Box 160-C, Concepción, Chile.
| | | | - Carlos A Villacis-Aguirre
- Biotechnology and Biopharmaceuticals Laboratory, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Víctor Lamas 1290, P.O. Box 160-C, Concepción, Chile.
| | - Matteo D'Este
- AO Research Institute Davos, Clavadelerstrasse 8, 7270, Davos, Switzerland
| | - Jorge R Toledo
- Biotechnology and Biopharmaceuticals Laboratory, Departamento de Fisiopatología, Facultad de Ciencias Biológicas, Universidad de Concepción, Víctor Lamas 1290, P.O. Box 160-C, Concepción, Chile.
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2
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Sun X, Guo Y, Zheng X, Bai Y, Lu Y, Yang X, Cai Z, Xu E, He Y, Heng BC, Xu M, Deng X, Zhang X. Optimizing the Electrical Microenvironment Provided by 3D Micropillar Topography on a Piezoelectric BaTiO 3 Substrate to Enhance Osseointegration. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2025; 37:e2414161. [PMID: 39564749 DOI: 10.1002/adma.202414161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 11/02/2024] [Indexed: 11/21/2024]
Abstract
The electrical properties of bone implant scaffolds are a pivotal factor in regulating cellular behavior and promoting osteogenesis. The previous study shows that built-in electric fields established between electropositive nanofilms and electronegative bone defect walls are beneficial for promoting bone defect healing. Considering that the physiological electrical microenvironment is spatially distributed in 3D, it is imperative to establish a 3D spatial charged microenvironment on bone scaffolds to optimize the efficacy of osseointegration. Nevertheless, this still poses a formidable challenge. Here, a bone repair strategy that utilizes micro-scale 3D topography is developed on a piezoelectric BaTiO3 (BTO) substrate to provide 3D spatial electrical stimulation. The BTO micropillar arrays, especially with a height of 50 µm and positive-charge distribution (50 µm positive), promote the spreading, cytoskeletal reorganization, focal adhesion maturation, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). They enhanced the clustering of mechanosensing integrin α5 in BMSCs. The biomimetic 3D spatial electrical microenvironment accelerated bone repair and osseointegration in a rat femoral diaphysis defect repair model. The study thus reveals that implants with a 3D spatial electrical microenvironment can significantly enhance osseointegration, thereby providing a new strategy to optimize the performance of electroactive biomaterials for tissue regenerative therapies.
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Affiliation(s)
- Xiaowen Sun
- Department of Dental Materials & Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
- Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Yaru Guo
- Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Xiaona Zheng
- Department of Dental Materials & Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
- National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, NMPA Key Laboratory for Dental Materials, Beijing Laboratory of Biomedical Materials & Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Yunyang Bai
- Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Yixuan Lu
- Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Xue Yang
- First Clinical Division, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Ziming Cai
- School of Materials Science and Physics, China University of Mining and Technology, Xuzhou, 221116, P. R. China
| | - Erxiang Xu
- State Key Lab of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, P. R. China
| | - Ying He
- Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Boon Chin Heng
- Department of Dental Materials & Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Mingming Xu
- Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Xuliang Deng
- Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
- National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, NMPA Key Laboratory for Dental Materials, Beijing Laboratory of Biomedical Materials & Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
| | - Xuehui Zhang
- Department of Dental Materials & Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
- National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, NMPA Key Laboratory for Dental Materials, Beijing Laboratory of Biomedical Materials & Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, P. R. China
- Oral Translational Medicine Research Center, Joint Training base for Shanxi Provincial Key Laboratory in Oral and Maxillofacial Repair, Reconstruction and Regeneration, The First People's Hospital of Jinzhong, Jinzhong, Shanxi, 030600, P. R. China
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Mahadeva M, Niestępski S, Kowacz M. Modifying membrane potential synchronously controls the somite's formation periodicity and growth. Dev Biol 2025; 517:317-326. [PMID: 39521163 DOI: 10.1016/j.ydbio.2024.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 10/22/2024] [Accepted: 11/06/2024] [Indexed: 11/16/2024]
Abstract
Coordination between periodicity of somite formation and somite growth is crucial for regular body pattern formation during somitogenesis. Yet, the specific mechanism that links the two processes remains unclear. Using chick embryos, we demonstrate that both temporal and spatial features can be simultaneously controlled by membrane potential (Vm) of somite-forming cells. Our findings show that somites hyperpolarize as they mature, displaying step-like changes in Vm observed between specific groups of somites, reflecting the reported onset of biochemical and structural changes within them. We modify Vm by changing chemical compositions of the microenvironment of the embryo. Alteration of Vm sets a new pace of somite formation (cell migration and self-assembly) and its concurrent growth (cell proliferation) without disturbing the somite's regular aspect ratio. Our results therefore suggest that Vm has the ability to orchestrate cell proliferation, migration and self-assembly - processes that are hallmarks of embryogenesis, tumorigenesis and tissue regeneration.
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Affiliation(s)
- Manohara Mahadeva
- Department of Reproductive Immunology & Pathology, Institute of Animal Reproduction and Food Research Polish Academy of Sciences, 10-748, Olsztyn, Poland.
| | - Sebastian Niestępski
- Department of Reproductive Immunology & Pathology, Institute of Animal Reproduction and Food Research Polish Academy of Sciences, 10-748, Olsztyn, Poland.
| | - Magdalena Kowacz
- Department of Reproductive Immunology & Pathology, Institute of Animal Reproduction and Food Research Polish Academy of Sciences, 10-748, Olsztyn, Poland.
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Xiao Y, Yang S, Sun Y, Sah RL, Wang J, Han C. Nanoscale Morphologies on the Surface of Substrates/Scaffolds Enhance Chondrogenic Differentiation of Stem Cells: A Systematic Review of the Literature. Int J Nanomedicine 2024; 19:12743-12768. [PMID: 39634196 PMCID: PMC11615010 DOI: 10.2147/ijn.s492020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Accepted: 11/13/2024] [Indexed: 12/07/2024] Open
Abstract
Nanoscale morphologies on the surface of substrates/scaffolds have gained considerable attention in cartilage tissue engineering for their potential to improve chondrogenic differentiation and cartilage regeneration outcomes by mimicking the topographical and biophysical properties of the extracellular matrix (ECM). To evaluate the influence of nanoscale surface morphologies on chondrogenic differentiation of stem cells and discuss available strategies, we systematically searched evidence according to the PRISMA guidelines on PubMed, Embase, Web of Science, and Cochrane (until April 2024) and registered on the OSF (osf.io/3kvdb). The inclusion criteria were (in vitro) studies reporting the chondrogenic differentiation outcomes of nanoscale morphologies on the surface of substrates/scaffolds. The risk of bias (RoB) was assessed using the JBI-adapted quasi-experimental study assessment tool. Out of 1530 retrieved articles, 14 studies met the inclusion criteria. The evidence suggests that nanoholes, nanogrills, nanoparticles with a diameter of 10-40nm, nanotubes with a diameter of 70-100nm, nanopillars with a height of 127-330nm, and hexagonal nanostructures with a periodicity of 302-733nm on the surface of substrates/scaffolds result in better cell adhesion, growth, and chondrogenic differentiation of stem cells compared to the smooth/unpatterned ones through increasing integrin expression. Large nanoparticles with 300-1200nm diameter promote pre-chondrogenic cellular aggregation. The synergistic effects of the surface nanoscale topography and other environmental physical characteristics, such as matrix stiffness, also play important in the chondrogenic differentiation of stem cells. The RoB was low in 86% (12/14) of studies and high in 14% (2/14). Our study demonstrates that nanomorphologies with specific controlled properties engineered on the surface of substrates/scaffolds enhance stem cells' chondrogenic differentiation, which may benefit cartilage regeneration. However, given the variability in experimental designs and lack of reporting across studies, the results should be interpreted with caution.
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Affiliation(s)
- Yi Xiao
- Thoracic Surgery Department, The China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of China
- Orthopedic Medical Center, the Second Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of China
| | - Shiyan Yang
- Orthopedic Medical Center, the Second Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of China
- Department of Head and Neck, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
| | - Yang Sun
- Orthopedic Medical Center, the Second Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of China
| | - Robert L Sah
- Department of Bioengineering, University of California–San Diego, La Jolla, CA, 92037, USA
- Center for Musculoskeletal Research, Institute of Engineering in Medicine, University of California–San Diego, La Jolla, CA, 92037, USA
| | - Jincheng Wang
- Orthopedic Medical Center, the Second Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of China
| | - Chunshan Han
- Thoracic Surgery Department, The China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of China
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Zhong S, Zheng L, Wu Y, Sun S, Luo Q, Song G, Lü D, Long M. Rotating culture regulates the formation of HepaRG-derived liver organoids via YAP translocation. BMC Biol 2024; 22:262. [PMID: 39548509 PMCID: PMC11568593 DOI: 10.1186/s12915-024-02062-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Accepted: 11/05/2024] [Indexed: 11/18/2024] Open
Abstract
BACKGROUND Liver organoid serves as an alternative model for liver pathophysiology in carbohydrate or lipid metabolism and xenobiotic metabolism transformation. Biomechanical cues including spaceflight mission can affect liver organoid construction and their related functions, but their underlying mechanisms are not fully understood yet. Here, a rotating cell culture device, namely Rotating Flat Chamber (RFC), was specifically designed for adhering cells or cell aggregated to elucidate the effects of altered gravity vector on HepaRG-derived liver organoids construction. RESULTS The organoids so formed under RFC presented the fast growth rate and large projection area. Meanwhile, the expressions of two pluripotency markers of SOX9 and CD44 were enhanced. This finding was positively correlated with the increased YAP expression and nuclear translocation as well as the elevated α4β6-integrin expression. Inhibition of YAP expression and nuclear translocation decreased the expression of SOX9 and CD44 under RFC, thereby attenuating the pluripotency of HepaRG-derived liver organoids. CONCLUSIONS In conclusion, we proposed a novel liver organoid construction method using rotating culture, by which the pluripotency of liver organoids so constructed is mediated by α4β6-integrin and YAP translocation. This work furthered the understanding in how the gravity vector orientation affects the construction of liver organoids and the related mechanotransductive pathways.
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Affiliation(s)
- Shaoyu Zhong
- Center for Biomechanics and Bioengineering, Beijing Key Laboratory of Engineered Construction and Mechanobiology and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, China
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China
| | - Lu Zheng
- Center for Biomechanics and Bioengineering, Beijing Key Laboratory of Engineered Construction and Mechanobiology and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, China
- School of Engineering Science, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Yi Wu
- Center for Biomechanics and Bioengineering, Beijing Key Laboratory of Engineered Construction and Mechanobiology and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, China
- School of Engineering Science, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Shujin Sun
- Center for Biomechanics and Bioengineering, Beijing Key Laboratory of Engineered Construction and Mechanobiology and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, China
- School of Engineering Science, University of Chinese Academy of Sciences, Beijing, 100049, China
| | - Qing Luo
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China
| | - Guanbin Song
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China
| | - Dongyuan Lü
- Center for Biomechanics and Bioengineering, Beijing Key Laboratory of Engineered Construction and Mechanobiology and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, China.
- School of Engineering Science, University of Chinese Academy of Sciences, Beijing, 100049, China.
| | - Mian Long
- Center for Biomechanics and Bioengineering, Beijing Key Laboratory of Engineered Construction and Mechanobiology and Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, China.
- School of Engineering Science, University of Chinese Academy of Sciences, Beijing, 100049, China.
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Yang T, Wang L, Ma H, Li K, Wang Y, Tang W, Wang Z, An M, Gao X, Xu L, Guo Y, Guo J, Liu Y, Wang H, Liu Y, Zhang Q. Role of Emerin in regulating fibroblast differentiation and migration at the substrate of stiffness coupled topology. Acta Biochim Biophys Sin (Shanghai) 2024; 56:1387-1400. [PMID: 38978507 PMCID: PMC11532208 DOI: 10.3724/abbs.2024094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Accepted: 02/26/2024] [Indexed: 07/10/2024] Open
Abstract
In hypertrophic scars, the differentiation and migration of fibroblasts are influenced by the extracellular matrix microenvironment, which includes factors such as stiffness, restraint, and tensile force. These mechanical stresses incite alterations in cell behavior, accompanied by cytoskeletal protein reorganization. However, the role of nucleo-skeletal proteins in this context remains underexplored. In this study, we use a polyacrylamide hydrogel (PAA) to simulate the mechanical stress experienced by cells in scar tissue and investigate the impact of Emerin on cell behavior. We utilize atomic force microscopy (AFM) and RNA interference technology to analyze cell differentiation, migration, and stiffness. Our findings reveal that rigid substrates and cellular restriction elevate Emerin expression and diminish differentiation. Conversely, reducing Emerin expression leads to attenuated cell differentiation, where stiffness and constraining factors exert no notable influence. Furthermore, a softening of cells and an enhanced migration rate are also markedly observed. These observations indicate that variations in nuclear skeletal proteins, prompted by diverse matrix microenvironments, play a pivotal role in the pathogenesis of hypertrophic scars (HSs). This research offers novel insights and a reference point for understanding scar fibrosis formation mechanisms and preventing fibrosis.
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Affiliation(s)
- Tiantian Yang
- College of Biomedical EngineeringTaiyuan University of TechnologyTaiyuan030024China
| | - Li Wang
- College of Biomedical EngineeringTaiyuan University of TechnologyTaiyuan030024China
| | - Haiyang Ma
- College of Biomedical EngineeringTaiyuan University of TechnologyTaiyuan030024China
| | - Kailun Li
- Trauma CenterTrauma OrthopaedicsZhouKou Orthopaedic HospitalZhoukou466000China
| | - Yajing Wang
- College of Biomedical EngineeringTaiyuan University of TechnologyTaiyuan030024China
| | - Wenjie Tang
- College of Biomedical EngineeringTaiyuan University of TechnologyTaiyuan030024China
| | - Zichen Wang
- College of Biomedical EngineeringTaiyuan University of TechnologyTaiyuan030024China
| | - Meiwen An
- College of Biomedical EngineeringTaiyuan University of TechnologyTaiyuan030024China
| | - Xiang Gao
- College of Biomedical EngineeringTaiyuan University of TechnologyTaiyuan030024China
| | - Ludan Xu
- College of Biomedical EngineeringTaiyuan University of TechnologyTaiyuan030024China
| | - Yunyun Guo
- College of Biomedical EngineeringTaiyuan University of TechnologyTaiyuan030024China
| | - Jiqiang Guo
- College of Biomedical EngineeringTaiyuan University of TechnologyTaiyuan030024China
- Shanxi Bethune Hospitalthe Third Hospital of Shanxi Medical UniversityTaiyuan030053China
| | - Yong Liu
- Dermatology DepartmentShanxi Bethune HospitalShanxi Academy of Medical SciencesTaiyuan030032China
| | - Hugen Wang
- Orthopaedics departmentthe First People’s Hospital of JinzhongJinzhong030600China
| | - Yang Liu
- College of Biomedical EngineeringTaiyuan University of TechnologyTaiyuan030024China
- Department of Nuclear Medicinethe First Hospital of Shanxi Medical UniversityTaiyuan030012China
| | - Quanyou Zhang
- College of Biomedical EngineeringTaiyuan University of TechnologyTaiyuan030024China
- Department of OrthopaedicsShanxi Medical UniversityTaiyuan030001China
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Soliman BG, Longoni A, Major GS, Lindberg GCJ, Choi YS, Zhang YS, Woodfield TBF, Lim KS. Harnessing Macromolecular Chemistry to Design Hydrogel Micro- and Macro-Environments. Macromol Biosci 2024; 24:e2300457. [PMID: 38035637 DOI: 10.1002/mabi.202300457] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Revised: 11/16/2023] [Indexed: 12/02/2023]
Abstract
Cell encapsulation within three-dimensional hydrogels is a promising approach to mimic tissues. However, true biomimicry of the intricate microenvironment, biophysical and biochemical gradients, and the macroscale hierarchical spatial organizations of native tissues is an unmet challenge within tissue engineering. This review provides an overview of the macromolecular chemistries that have been applied toward the design of cell-friendly hydrogels, as well as their application toward controlling biophysical and biochemical bulk and gradient properties of the microenvironment. Furthermore, biofabrication technologies provide the opportunity to simultaneously replicate macroscale features of native tissues. Biofabrication strategies are reviewed in detail with a particular focus on the compatibility of these strategies with the current macromolecular toolkit described for hydrogel design and the challenges associated with their clinical translation. This review identifies that the convergence of the ever-expanding macromolecular toolkit and technological advancements within the field of biofabrication, along with an improved biological understanding, represents a promising strategy toward the successful tissue regeneration.
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Affiliation(s)
- Bram G Soliman
- School of Materials Science and Engineering, University of New South Wales, Sydney, 2052, Australia
| | - Alessia Longoni
- Department of Orthopedics, University Medical Center Utrecht, Utrecht, 3584CX, The Netherlands
| | - Gretel S Major
- Department of Orthopedic Surgery and Musculoskeletal Medicine, University of Otago, Christchurch, 8011, New Zealand
| | - Gabriella C J Lindberg
- Phil and Penny Knight Campus for Accelerating Scientific Impact Department of Bioengineering, University of Oregon, Eugene, OR, 97403, USA
| | - Yu Suk Choi
- School of Human Sciences, The University of Western Australia, Perth, 6009, Australia
| | - Yu Shrike Zhang
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02115, USA
| | - Tim B F Woodfield
- Department of Orthopedic Surgery and Musculoskeletal Medicine, University of Otago, Christchurch, 8011, New Zealand
| | - Khoon S Lim
- Department of Orthopedic Surgery and Musculoskeletal Medicine, University of Otago, Christchurch, 8011, New Zealand
- School of Medical Sciences, University of Sydney, Sydney, 2006, Australia
- Charles Perkins Centre, University of Sydney, Sydney, 2006, Australia
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8
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Chen H, Fan Y, Shi Z, Liu C, Ran M, Zhai J, Wu J, Wong TM, Ning C, Yu P. NIR-responsive micropatterned nanocomposite functionalized implant for sequential antibacterial and osteogenesis. Colloids Surf B Biointerfaces 2024; 235:113748. [PMID: 38306804 DOI: 10.1016/j.colsurfb.2024.113748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 12/19/2023] [Accepted: 01/03/2024] [Indexed: 02/04/2024]
Abstract
The long-term durability of the implant is influenced by two significant clinical challenges, namely bacterial infection and fixation loosening. Conventional implant materials have failed to meet the demands of the dynamic process of infectious bone repair, which necessitates early-stage bacterial sterilization and a conducive environment for late-stage osteogenesis. Consequently, there is an urgent requirement for an implant material that can sequentially regulate antibacterial properties and promote osteogenesis. The study aimed to develop a micropatterned graphene oxide nanocomposite on titanium implant (M-NTO/GO) for the sequential management of bacterial infection and osteogenic promotion. M-NTO/GO exhibited a micropattern nanostructure surface and demonstrated responsiveness to near-infrared (NIR) light. Upon NIR light irradiation, M-NTO/GO exhibited effective antibacterial properties, achieving antibacterial rates of 96.9% and 98.6% against E. coli and S. aureus, respectively. Under no-light condition, the micropatterned topography of M-NTO/GO exhibited the ability to induce directed cell growth, enhance cell adhesion and spreading, and facilitate osteogenic differentiation. These findings suggest the successful development of a functionalized micropatterned nanocomposite implant capable of sequentially regulating antibacterial and osteogenesis activity. Consequently, this highly effective strategy holds promise for expanding the potential applications of orthopedic implants.
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Affiliation(s)
- Haoyan Chen
- School of Material Science and Engineering, National Engineering Research Center for Tissue Restoration and Reconstruction, GuangDong Engineering Technology Research Center of Metallic Materials Surface Functionalization, South China University of Technology, Guangzhou 510641, China
| | - Youzhun Fan
- School of Material Science and Engineering, National Engineering Research Center for Tissue Restoration and Reconstruction, GuangDong Engineering Technology Research Center of Metallic Materials Surface Functionalization, South China University of Technology, Guangzhou 510641, China
| | - Zhifeng Shi
- National Engineering Research Center for Tissue Restoration and Reconstruction, Key Laboratory of Biomedical Engineering of Guangdong Province, Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China
| | - Chengli Liu
- School of Material Science and Engineering, National Engineering Research Center for Tissue Restoration and Reconstruction, GuangDong Engineering Technology Research Center of Metallic Materials Surface Functionalization, South China University of Technology, Guangzhou 510641, China
| | - Maofei Ran
- School of Material Science and Engineering, National Engineering Research Center for Tissue Restoration and Reconstruction, GuangDong Engineering Technology Research Center of Metallic Materials Surface Functionalization, South China University of Technology, Guangzhou 510641, China
| | - Jinxia Zhai
- School of Material Science and Engineering, National Engineering Research Center for Tissue Restoration and Reconstruction, GuangDong Engineering Technology Research Center of Metallic Materials Surface Functionalization, South China University of Technology, Guangzhou 510641, China
| | - Jun Wu
- Department of Orthopaedics and Traumatology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam 999077, China
| | - Tak Man Wong
- Department of Orthopaedics and Traumatology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam 999077, China
| | - Chengyun Ning
- School of Material Science and Engineering, National Engineering Research Center for Tissue Restoration and Reconstruction, GuangDong Engineering Technology Research Center of Metallic Materials Surface Functionalization, South China University of Technology, Guangzhou 510641, China
| | - Peng Yu
- School of Material Science and Engineering, National Engineering Research Center for Tissue Restoration and Reconstruction, GuangDong Engineering Technology Research Center of Metallic Materials Surface Functionalization, South China University of Technology, Guangzhou 510641, China.
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9
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Malandain N, Sanz-Fraile H, Farré R, Otero J, Roig A, Laromaine A. Cell-Laden 3D Hydrogels of Type I Collagen Incorporating Bacterial Nanocellulose Fibers. ACS APPLIED BIO MATERIALS 2023; 6:3638-3647. [PMID: 37669535 PMCID: PMC10521014 DOI: 10.1021/acsabm.3c00126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 08/08/2023] [Indexed: 09/07/2023]
Abstract
There is a growing interest in developing natural hydrogel-based scaffolds to culture cells in a three-dimensional (3D) millieu that better mimics the in vivo cells' microenvironment. A promising approach is to use hydrogels from animal tissues, such as decellularized extracellular matrices; however, they usually exhibit suboptimal mechanical properties compared to native tissue and their composition with hundreds of different protein complicates to elucidate which stimulus triggers cell's responses. As simpler scaffolds, type I collagen hydrogels are used to study cell behavior in mechanobiology even though they are also softer than native tissues. In this work, type I collagen is mixed with bacterial nanocellulose fibers (BCf) to develop reinforced scaffolds with mechanical properties suitable for 3D cell culture. BCf were produced from blended pellicles biosynthesized from Komagataeibacter xylinus. Then, BCf were mixed with concentrated collagen from rat-tail tendons to form composite hydrogels. Confocal laser scanning microscopy and scanning electron microscopy images confirmed the homogeneous macro- and microdistribution of both natural polymers. Porosity analysis confirmed that BCf do not disrupt the scaffold structure. Tensile strength and rheology measurements demonstrated the reinforcement action of BCf (43% increased stiffness) compared to the collagen hydrogel while maintaining the same viscoelastic response. Additionally, this reinforcement of collagen hydrogels with BCf offers the possibility to mix cells before gelation and then proceed to the culture of the 3D cell scaffolds. We obtained scaffolds with human bone marrow-derived mesenchymal stromal cells or human fibroblasts within the composite hydrogels, allowing a homogeneous 3D viable culture for at least 7 days. A smaller surface shrinkage in the reinforced hydrogels compared to type I collagen hydrogels confirmed the strengthening of the composite hydrogels. These collagen hydrogels reinforced with BCf might emerge as a promising platform for 3D in vitro organ modeling, tissue-engineering applications, and suitable to conduct fundamental mechanobiology studies.
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Affiliation(s)
- Nanthilde Malandain
- Institut
de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus UAB, 08193 Bellaterra, Spain
- Unitat
de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències
de la Salut, Universitat de Barcelona, 08036 Barcelona, Spain
| | - Hector Sanz-Fraile
- Unitat
de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències
de la Salut, Universitat de Barcelona, 08036 Barcelona, Spain
| | - Ramon Farré
- Unitat
de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències
de la Salut, Universitat de Barcelona, 08036 Barcelona, Spain
- CIBER
de Enfermedades Respiratorias, 28029 Madrid, Spain
- Institut
d’Investigacions Biomèdiques August Pi i Sunyer, 08036 Barcelona, Spain
| | - Jorge Otero
- Unitat
de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències
de la Salut, Universitat de Barcelona, 08036 Barcelona, Spain
- CIBER
de Enfermedades Respiratorias, 28029 Madrid, Spain
- The
Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain
| | - Anna Roig
- Institut
de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus UAB, 08193 Bellaterra, Spain
| | - Anna Laromaine
- Institut
de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus UAB, 08193 Bellaterra, Spain
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10
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Drewry MD, Rothermund K, Syed-Picard FN. Topographical and Chemical Inductive Cues Synergistically Enhance the Schwann Cell Differentiation of Aligned Dental Pulp Stem Cell Sheets. J Tissue Eng Regen Med 2023; 2023:7958770. [PMID: 40226400 PMCID: PMC11918939 DOI: 10.1155/2023/7958770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 05/23/2023] [Accepted: 06/06/2023] [Indexed: 04/15/2025]
Abstract
Peripheral nerves have an inherent capacity for regeneration, but these Schwann cell-mediated mechanisms are insufficient for severe injuries. With current clinical treatments, slow regeneration and aberrant reinnervation result in poor functional outcomes. Dental pulp stem cells (DPSCs) offer a promising source of therapeutic neurotrophic factors (NTFs), growth factors that stimulate axon regeneration. Previously, we established that DPSCs can generate scaffold-free sheets with a linearly aligned extracellular matrix (ECM). These sheets provide trophic cues via the DPSCs and directional cues through the aligned ECM to both accelerate and orient axon outgrowth, thus providing a biomaterial capable of addressing the current clinical challenges. DPSCs have a propensity for differentiating into Schwann cells (SC-DPSCs), further enhancing their endogenous NTF expression. Here, we evaluated the effect of inducing SC differentiation on the neuroregenerative bioactivity of our DPSC sheets. These sheets were formed on substrates with linear microgrooves to direct the cells to deposit an aligned ECM. Inducing differentiation using an SC differentiation medium (SCDM) increased NTF expression 2-fold compared to unaligned uDPSC sheets, and this effect was amplified in linearly oriented SC-DPSC sheets by up to 8-fold. Furthermore, these aligned SC-DPSC sheets remodeled the sheet ECM to more closely emulate a regenerative neural microenvironment, expressing 8-fold and 2 × 107-fold more collagen IV and laminin, respectively, than unaligned uDPSC sheets. These data demonstrate that the chemical cues of the SCDM and the mechanotransductive cues of the aligned cell sheet synergistically enhanced the differentiation of DPSCs into repair SC-like cells. To evaluate their functional effects on neuritogenesis, the DPSC sheets were directly cocultured with neuronally differentiated neuroblastoma SH-SY5Y cells. In this in vitro culture system, the aligned SC-DPSC sheets promoted oriented neurite-like outgrowth similar to aligned uninduced DPSC sheets and increased collateral branching, which may emulate stages associated with natural SC-mediated repair processes. Therefore, linearly aligned SC-DPSC sheets have the potential to both promote nerve regeneration and reduce aberrant reinnervation, thus providing a promising biomaterial for applications to improve the treatment of peripheral nerve injury.
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Affiliation(s)
- Michelle D. Drewry
- Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA
- Center for Craniofacial Regeneration, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Kristi Rothermund
- Center for Craniofacial Regeneration, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA
| | - Fatima N. Syed-Picard
- Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA
- Center for Craniofacial Regeneration, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA
- Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA
- McGowan Institute for Regenerative Medicine, Pittsburgh, PA, USA
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11
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Schamberger B, Ziege R, Anselme K, Ben Amar M, Bykowski M, Castro APG, Cipitria A, Coles RA, Dimova R, Eder M, Ehrig S, Escudero LM, Evans ME, Fernandes PR, Fratzl P, Geris L, Gierlinger N, Hannezo E, Iglič A, Kirkensgaard JJK, Kollmannsberger P, Kowalewska Ł, Kurniawan NA, Papantoniou I, Pieuchot L, Pires THV, Renner LD, Sageman-Furnas AO, Schröder-Turk GE, Sengupta A, Sharma VR, Tagua A, Tomba C, Trepat X, Waters SL, Yeo EF, Roschger A, Bidan CM, Dunlop JWC. Curvature in Biological Systems: Its Quantification, Emergence, and Implications across the Scales. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2023; 35:e2206110. [PMID: 36461812 DOI: 10.1002/adma.202206110] [Citation(s) in RCA: 52] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 11/22/2022] [Indexed: 06/17/2023]
Abstract
Surface curvature both emerges from, and influences the behavior of, living objects at length scales ranging from cell membranes to single cells to tissues and organs. The relevance of surface curvature in biology is supported by numerous experimental and theoretical investigations in recent years. In this review, first, a brief introduction to the key ideas of surface curvature in the context of biological systems is given and the challenges that arise when measuring surface curvature are discussed. Giving an overview of the emergence of curvature in biological systems, its significance at different length scales becomes apparent. On the other hand, summarizing current findings also shows that both single cells and entire cell sheets, tissues or organisms respond to curvature by modulating their shape and their migration behavior. Finally, the interplay between the distribution of morphogens or micro-organisms and the emergence of curvature across length scales is addressed with examples demonstrating these key mechanistic principles of morphogenesis. Overall, this review highlights that curved interfaces are not merely a passive by-product of the chemical, biological, and mechanical processes but that curvature acts also as a signal that co-determines these processes.
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Affiliation(s)
- Barbara Schamberger
- Department of the Chemistry and Physics of Materials, Paris-Lodron University of Salzburg, 5020, Salzburg, Austria
| | - Ricardo Ziege
- Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, 14476, Potsdam, Germany
| | - Karine Anselme
- IS2M (CNRS - UMR 7361), Université de Haute-Alsace, F-68100, Mulhouse, France
- Université de Strasbourg, F-67081, Strasbourg, France
| | - Martine Ben Amar
- Department of Physics, Laboratoire de Physique de l'Ecole Normale Supérieure, 24 rue Lhomond, 75005, Paris, France
| | - Michał Bykowski
- Department of Plant Anatomy and Cytology, Faculty of Biology, University of Warsaw, 02-096, Warsaw, Poland
| | - André P G Castro
- IDMEC, Instituto Superior Técnico, Universidade de Lisboa, 1049-001, Lisboa, Portugal
- ESTS, Instituto Politécnico de Setúbal, 2914-761, Setúbal, Portugal
| | - Amaia Cipitria
- IS2M (CNRS - UMR 7361), Université de Haute-Alsace, F-68100, Mulhouse, France
- Group of Bioengineering in Regeneration and Cancer, Biodonostia Health Research Institute, 20014, San Sebastian, Spain
- IKERBASQUE, Basque Foundation for Science, 48009, Bilbao, Spain
| | - Rhoslyn A Coles
- Cluster of Excellence, Matters of Activity, Humboldt-Universität zu Berlin, 10178, Berlin, Germany
| | - Rumiana Dimova
- Department of Theory and Bio-Systems, Max Planck Institute of Colloids and Interfaces, 14476, Potsdam, Germany
| | - Michaela Eder
- Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, 14476, Potsdam, Germany
| | - Sebastian Ehrig
- Max Delbrück Center for Molecular Medicine, 13125, Berlin, Germany
- Berlin Institute for Medical Systems Biology, 10115, Berlin, Germany
| | - Luis M Escudero
- Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla and Departamento de Biología Celular, Universidad de Sevilla, 41013, Seville, Spain
- Biomedical Network Research Centre on Neurodegenerative Diseases (CIBERNED), 28031, Madrid, Spain
| | - Myfanwy E Evans
- Institute for Mathematics, University of Potsdam, 14476, Potsdam, Germany
| | - Paulo R Fernandes
- IDMEC, Instituto Superior Técnico, Universidade de Lisboa, 1049-001, Lisboa, Portugal
| | - Peter Fratzl
- Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, 14476, Potsdam, Germany
| | - Liesbet Geris
- Biomechanics Research Unit, GIGA In Silico Medicine, University of Liège, 4000, Liège, Belgium
| | - Notburga Gierlinger
- Institute of Biophysics, Department of Nanobiotechnology, University of Natural Resources and Life Sciences Vienna (Boku), 1190, Vienna, Austria
| | - Edouard Hannezo
- Institute of Science and Technology Austria, 3400, Klosterneuburg, Austria
| | - Aleš Iglič
- Laboratory of Physics, Faculty of Electrical engineering, University of Ljubljana, Tržaška 25, SI-1000, Ljubljana, Slovenia
| | - Jacob J K Kirkensgaard
- Condensed Matter Physics, Niels Bohr Institute, University of Copenhagen, Universitetsparken 5, 2100, København Ø, Denmark
- Ingredients and Dairy Technology, Department of Food Science, University of Copenhagen, Rolighedsvej 26, 1958, Frederiksberg, Denmark
| | - Philip Kollmannsberger
- Center for Computational and Theoretical Biology, University of Würzburg, 97074, Würzburg, Germany
| | - Łucja Kowalewska
- Department of Plant Anatomy and Cytology, Faculty of Biology, University of Warsaw, 02-096, Warsaw, Poland
| | - Nicholas A Kurniawan
- Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, 5600 MB, Eindhoven, The Netherlands
| | - Ioannis Papantoniou
- Prometheus Division of Skeletal Tissue Engineering, KU Leuven, O&N1, Herestraat 49, PB 813, 3000, Leuven, Belgium
- Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, O&N1, Herestraat 49, PB 813, 3000, Leuven, Belgium
- Institute of Chemical Engineering Sciences, Foundation for Research and Technology (FORTH), Stadiou Str., 26504, Patras, Greece
| | - Laurent Pieuchot
- IS2M (CNRS - UMR 7361), Université de Haute-Alsace, F-68100, Mulhouse, France
- Université de Strasbourg, F-67081, Strasbourg, France
| | - Tiago H V Pires
- IDMEC, Instituto Superior Técnico, Universidade de Lisboa, 1049-001, Lisboa, Portugal
| | - Lars D Renner
- Leibniz Institute of Polymer Research and the Max Bergmann Center of Biomaterials, 01069, Dresden, Germany
| | | | - Gerd E Schröder-Turk
- School of Physics, Chemistry and Mathematics, Murdoch University, 90 South St, Murdoch, WA, 6150, Australia
- Department of Materials Physics, Research School of Physics, The Australian National University, Canberra, ACT, 2600, Australia
| | - Anupam Sengupta
- Physics of Living Matter, Department of Physics and Materials Science, University of Luxembourg, L-1511, Luxembourg City, Grand Duchy of Luxembourg
| | - Vikas R Sharma
- Department of the Chemistry and Physics of Materials, Paris-Lodron University of Salzburg, 5020, Salzburg, Austria
| | - Antonio Tagua
- Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla and Departamento de Biología Celular, Universidad de Sevilla, 41013, Seville, Spain
- Biomedical Network Research Centre on Neurodegenerative Diseases (CIBERNED), 28031, Madrid, Spain
| | - Caterina Tomba
- Univ Lyon, CNRS, INSA Lyon, Ecole Centrale de Lyon, Université Claude Bernard Lyon 1, CPE Lyon, INL, UMR5270, 69622, Villeurbanne, France
| | - Xavier Trepat
- ICREA at the Institute for Bioengineering of Catalonia, The Barcelona Institute for Science and Technology, 08028, Barcelona, Spain
- Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 08028, Barcelona, Spain
| | - Sarah L Waters
- Mathematical Institute, University of Oxford, OX2 6GG, Oxford, UK
| | - Edwina F Yeo
- Mathematical Institute, University of Oxford, OX2 6GG, Oxford, UK
| | - Andreas Roschger
- Department of the Chemistry and Physics of Materials, Paris-Lodron University of Salzburg, 5020, Salzburg, Austria
| | - Cécile M Bidan
- Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, 14476, Potsdam, Germany
| | - John W C Dunlop
- Department of the Chemistry and Physics of Materials, Paris-Lodron University of Salzburg, 5020, Salzburg, Austria
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12
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Kim MJ, Park JH, Lee JH, Kim H, Choi HJ, Lee HC, Lee JH, Byun JH, Oh SH. Bioactive Porous Particles as Biological and Physical Stimuli for Bone Regeneration. ACS Biomater Sci Eng 2022; 8:5233-5244. [PMID: 36384281 DOI: 10.1021/acsbiomaterials.2c00664] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Even though bony defects can be recovered to their original condition with full functionality, critical-sized bone injuries continue to be a challenge in clinical fields due to deficiencies in the scaffolding matrix and growth factors at the injury region. In this study, we prepared bone morphogenetic protein-2 (BMP-2)-loaded porous particles as a bioactive bone graft for accelerated bone regeneration. The porous particles with unique leaf-stacked morphology (LSS particles) were fabricated by a simple cooling procedure of hot polycaprolactone (PCL) solution. The unique leaf-stacked structure in the LSS particles provided a large surface area and complex release path for the sufficient immobilization of BMP-2 and sustained release of BMP-2 for 26 days. The LSS was also recognized as a topographical cue for cell adhesion and differentiation. In in vitro cell culture and in vivo animal study using a canine mandible defect model, BMP-2-immobilized LSS particles provided a favorable environment for osteogenic differentiation of stem cells and bone regeneration. In vitro study suggests a dual stimulus of bone mineral-like (leaf-stacked) structure (a physical cue) and continuously supplied BMP-2 (a biological cue) to be the cause of this improved healing outcome. Thus, LSS particles containing BMP-2 can be a promising bioactive grafting material for effective new bone formation.
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Affiliation(s)
- Min Ji Kim
- Department of Nanobiomedical Science, Dankook University, Cheonan 31116, Republic of Korea
| | - Jin-Ho Park
- Department of Oral and Maxillofacial Surgery, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Republic of Korea.,Department of Convergence Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea
| | - Jae-Hoon Lee
- Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea
| | - Hyeonjo Kim
- Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea
| | - Hyeon-Jong Choi
- Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea
| | - Hee-Chun Lee
- Department of Veterinary Medical Imaging, College of Veterinary Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea
| | - Jin Ho Lee
- Department of Advanced Materials, Hannam University, Daejeon 34054, Republic of Korea
| | - June-Ho Byun
- Department of Oral and Maxillofacial Surgery, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Republic of Korea.,Department of Convergence Medical Science, Gyeongsang National University, Jinju 52727, Republic of Korea
| | - Se Heang Oh
- Department of Nanobiomedical Science, Dankook University, Cheonan 31116, Republic of Korea
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13
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Ribeiro S, Pugliese E, Korntner SH, Fernandes EM, Gomes ME, Reis RL, O'Riordan A, Bayon Y, Zeugolis DI. Assessing the combined effect of surface topography and substrate rigidity in human bone marrow stem cell cultures. Eng Life Sci 2022; 22:619-633. [PMID: 36247829 PMCID: PMC9550738 DOI: 10.1002/elsc.202200029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 08/08/2022] [Accepted: 08/10/2022] [Indexed: 11/11/2022] Open
Abstract
The combined effect of surface topography and substrate rigidity in stem cell cultures is still under-investigated, especially when biodegradable polymers are used. Herein, we assessed human bone marrow stem cell response on aliphatic polyester substrates as a function of anisotropic grooved topography and rigidity (7 and 12 kPa). Planar tissue culture plastic (TCP, 3 GPa) and aliphatic polyester substrates were used as controls. Cell morphology analysis revealed that grooved substrates caused nuclei orientation/alignment in the direction of the grooves. After 21 days in osteogenic and chondrogenic media, the 3 GPa TCP and the grooved 12 kPa substrate induced significantly higher calcium deposition and alkaline phosphatase (ALP) activity and glycosaminoglycan (GAG) deposition, respectively, than the other groups. After 14 days in tenogenic media, the 3 GPa TCP upregulated four and downregulated four genes; the planar 7 kPa substrate upregulated seven genes and downregulated one gene; and the grooved 12 kPa substrate upregulated seven genes and downregulated one gene. After 21 days in adipogenic media, the softest (7 kPa) substrates induced significantly higher oil droplet deposition than the other substrates and the grooved substrate induced significantly higher droplet deposition than the planar. Our data pave the way for more rational design of bioinspired constructs.
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Affiliation(s)
- Sofia Ribeiro
- MedtronicSofradim ProductionTrevouxFrance
- RegenerativeModular & Developmental Engineering Laboratory (REMODEL) and Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM)National University of Ireland Galway (NUI Galway)GalwayIreland
| | - Eugenia Pugliese
- RegenerativeModular & Developmental Engineering Laboratory (REMODEL) and Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM)National University of Ireland Galway (NUI Galway)GalwayIreland
| | - Stefanie H. Korntner
- RegenerativeModular & Developmental Engineering Laboratory (REMODEL) and Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM)National University of Ireland Galway (NUI Galway)GalwayIreland
| | - Emanuel M. Fernandes
- 3B's Research GroupI3Bs – Research Institute on BiomaterialsBiodegradables and BiomimeticsUniversity of MinhoHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineAveParkParque de Ciência e TecnologiaZona Industrial da GandraBarcoGuimarãesPortugal
- ICVS/3B's – PT Government Associate LaboratoryBraga/GuimarãesPortugal
| | - Manuela E. Gomes
- 3B's Research GroupI3Bs – Research Institute on BiomaterialsBiodegradables and BiomimeticsUniversity of MinhoHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineAveParkParque de Ciência e TecnologiaZona Industrial da GandraBarcoGuimarãesPortugal
- ICVS/3B's – PT Government Associate LaboratoryBraga/GuimarãesPortugal
| | - Rui L. Reis
- 3B's Research GroupI3Bs – Research Institute on BiomaterialsBiodegradables and BiomimeticsUniversity of MinhoHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineAveParkParque de Ciência e TecnologiaZona Industrial da GandraBarcoGuimarãesPortugal
- ICVS/3B's – PT Government Associate LaboratoryBraga/GuimarãesPortugal
| | | | - Yves Bayon
- MedtronicSofradim ProductionTrevouxFrance
| | - Dimitrios I. Zeugolis
- RegenerativeModular & Developmental Engineering Laboratory (REMODEL) and Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM)National University of Ireland Galway (NUI Galway)GalwayIreland
- RegenerativeModular & Developmental Engineering Laboratory (REMODEL)Charles Institute of DermatologyConway Institute of Biomolecular & Biomedical Research and School of Mechanical & Materials EngineeringUniversity College Dublin (UCD)DublinIreland
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14
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Zhang Y, Habibovic P. Delivering Mechanical Stimulation to Cells: State of the Art in Materials and Devices Design. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2022; 34:e2110267. [PMID: 35385176 DOI: 10.1002/adma.202110267] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 03/19/2022] [Indexed: 06/14/2023]
Abstract
Biochemical signals, such as growth factors, cytokines, and transcription factors are known to play a crucial role in regulating a variety of cellular activities as well as maintaining the normal function of different tissues and organs. If the biochemical signals are assumed to be one side of the coin, the other side comprises biophysical cues. There is growing evidence showing that biophysical signals, and in particular mechanical cues, also play an important role in different stages of human life ranging from morphogenesis during embryonic development to maturation and maintenance of tissue and organ function throughout life. In order to investigate how mechanical signals influence cell and tissue function, tremendous efforts have been devoted to fabricating various materials and devices for delivering mechanical stimuli to cells and tissues. Here, an overview of the current state of the art in the design and development of such materials and devices is provided, with a focus on their design principles, and challenges and perspectives for future research directions are highlighted.
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Affiliation(s)
- Yonggang Zhang
- Department of Instructive Biomaterials Engineering, Maastricht University, MERLN Institute for Technology-Inspired Regenerative Medicine, Universiteitssingel 40, Maastricht, 6229 ER, The Netherlands
| | - Pamela Habibovic
- Department of Instructive Biomaterials Engineering, Maastricht University, MERLN Institute for Technology-Inspired Regenerative Medicine, Universiteitssingel 40, Maastricht, 6229 ER, The Netherlands
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15
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Seraji AA, Goharpey F, Khademzadeh Yeganeh J. Highly crystallized and tough polylactic acid through addition of surface modified cellulose nanocrystals. J Appl Polym Sci 2022. [DOI: 10.1002/app.52871] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Amir Abbas Seraji
- Polymer & Color Engineering Department Amirkabir University of Technology Tehran Iran
| | - Fatemeh Goharpey
- Polymer & Color Engineering Department Amirkabir University of Technology Tehran Iran
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16
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Liu Y, Li T, Sun M, Cheng Z, Jia W, Jiao K, Wang S, Jiang K, Yang Y, Dai Z, Liu L, Liu G, Luo Y. ZIF-8 modified multifunctional injectable photopolymerizable GelMA hydrogel for the treatment of periodontitis. Acta Biomater 2022; 146:37-48. [PMID: 35364317 DOI: 10.1016/j.actbio.2022.03.046] [Citation(s) in RCA: 107] [Impact Index Per Article: 35.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 03/23/2022] [Accepted: 03/24/2022] [Indexed: 12/14/2022]
Abstract
Periodontitis is a chronic inflammatory disease caused by plaque that leads to alveolar bone resorption. In the treatment of periodontitis, it is necessary to reduce the bacterial load and promote alveolar bone regeneration. In this study, zeolitic imidazolate framework-8 (ZIF-8) is used in the treatment of periodontitis, and an injectable photopolymerizable ZIF-8/gelatin methacryloyl (GelMA) composite hydrogel (GelMA-Z) is constructed. We confirm that ZIF-8 nanoparticles are successfully loaded into GelMA, which demonstrates fluidity and photopolymerizability. GelMA-Z continuously releases Zn2+ and shows good cytocompatibility. In vitro, GelMA-Z can effectively upregulate the expression of osteogenesis-related genes and proteins, increase alkaline phosphatase activity, promote extracellular matrix mineralization by rat bone mesenchymal stem cells, and exert an obvious antibacterial effect against Porphyromonas gingivalis. In vivo, GelMA-Z reduces the bacterial load, relieves inflammation and promotes alveolar bone regeneration in a rat model. The above results show that GelMA-Z has potential prospects in the treatment of periodontitis. STATEMENT OF SIGNIFICANCE: Various methods have been explored for the treatment of periodontitis. However, current regiments have difficulty achieving ideal alveolar bone regeneration. In this study, we constructed a zeolitic imidazolate framework-8 (ZIF-8)/gelatin methacryloyl (GelMA) composite hydrogel (GelMA-Z). (1) The injectable and photopolymerizable GelMA-Z showed biocompatibility in vitro and in vivo. (2) GelMA-Z continually released zinc ions to promote the osteogenic differentiation of bone mesenchymal stem cells and kill bacteria in vitro. (3) In a rat model, the GelMA-Z pregel solution was used to fill the periodontal pocket and then crosslinked by UV exposure. GelMA-Z can stably remain in the periodontal pocket to reduce the bacterial load, relieve inflammation and promote alveolar bone regeneration. In conclusion, GelMA-Z has great potential for use in the treatment of periodontitis, especially in promoting alveolar bone regeneration.
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Affiliation(s)
- Yun Liu
- Department of Stomatology, The Second Hospital of Jilin University, Changchun 130000, China
| | - Ting Li
- Department of Gastroenterology, Affiliated Hospital of Changchun University of Chinese Medicine, Changchun 130000, China
| | - Maolei Sun
- Department of Stomatology, The Second Hospital of Jilin University, Changchun 130000, China
| | - Zhiqiang Cheng
- College of Resources and Environment, Jilin Agriculture University, Changchun 130000, China
| | - Wenyuan Jia
- Department of Orthopedics, The Second Hospital of Jilin University, Changchun 130000, China
| | - Kun Jiao
- Department of Stomatology, The Second Hospital of Jilin University, Changchun 130000, China
| | - Shaoru Wang
- Department of Stomatology, The Second Hospital of Jilin University, Changchun 130000, China
| | - Kongzhao Jiang
- Department of Stomatology, The Second Hospital of Jilin University, Changchun 130000, China
| | - Yuheng Yang
- Department of Orthopedics, The Second Hospital of Jilin University, Changchun 130000, China
| | - Zhihui Dai
- Department of Stomatology, The Second Hospital of Jilin University, Changchun 130000, China
| | - Liping Liu
- Department of Stomatology, The Second Hospital of Jilin University, Changchun 130000, China
| | - Guomin Liu
- Department of Orthopedics, The Second Hospital of Jilin University, Changchun 130000, China.
| | - Yungang Luo
- Department of Stomatology, The Second Hospital of Jilin University, Changchun 130000, China.
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17
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Zhang X, Zhang T, Liu B, Zhang Y, Ji Z, Wang X. Effects of Biomimetic Micropatterned Surfaces on the Adhesion and Morphology of Cervical Cancer Cells. ACS OMEGA 2022; 7:19913-19919. [PMID: 35722016 PMCID: PMC9202008 DOI: 10.1021/acsomega.2c01703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 05/17/2022] [Indexed: 06/15/2023]
Abstract
It has been demonstrated that micropatterned surfaces have an important influence on modulating cellular behavior. In recent years, with the rapid development of microfabrication techniques and in-depth study of nature, an increasing number of patterned structures imitating natural organisms have been successfully fabricated and widely evaluated. However, there are only a few reports about biomimetic patterned microstructures in biologically related fields. In our work, micropatterned polydimethylsiloxane (PDMS) was fabricated by mimicking the surface microstructures of natural Trifolium and Parthenocissus tricuspidata leaves using the template duplication method. The interactions between the two types of biomimetic micro-PDMS surfaces and two kinds of human cervical cancer cells (HeLa and SiHa) were investigated. HeLa and SiHa cells cultured on the two micropatterned PDMS samples exhibited more stretchable morphology, higher diffusion, and a much lower nuclear/cytoplasmic ratio than those cultured on flat PDMS surfaces, indicating a higher adhesion area of the cells. Both of the micro-PDMS substrates were found to induce significantly different morphological changes between HeLa and SiHa cells. This suggests that the micropatterned structure affects cell adhesion and morphology correlated with their surface geometric structure and roughness. The results reveal that biomimetic micropatterned surfaces from natural leaves significantly regulate the morphology and adhesion behavior of cervical cancer cells and are believed to be the new platforms for investigating the interaction between cells and substrates.
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Affiliation(s)
- Xiaohui Zhang
- School
of Stomatology, Key Laboratory of Oral Diseases of Gansu Province, Northwest Minzu University, Lanzhou 730000, China
| | - Ting Zhang
- School/Hospital
of Stomatology Lanzhou University, Lanzhou 730000, China
| | - Bin Liu
- School/Hospital
of Stomatology Lanzhou University, Lanzhou 730000, China
| | - Yun Zhang
- Lanzhou
Stomatology Hospital, Lanzhou 730000, China
| | - Zhongying Ji
- State
Key Laboratory of Solid Lubrication, , Lanzhou
Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China
- Yantai
Zhongke Research Institute of Advanced Materials and Green Chemical
Engineering, Yantai 264006, China
| | - Xiaolong Wang
- State
Key Laboratory of Solid Lubrication, , Lanzhou
Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China
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18
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Entezari M, Mozafari M, Bakhtiyari M, Moradi F, Bagher Z, Soleimani M. Three-dimensional-printed polycaprolactone/polypyrrole conducting scaffolds for differentiation of human olfactory ecto-mesenchymal stem cells into Schwann cell-like phenotypes and promotion of neurite outgrowth. J Biomed Mater Res A 2022; 110:1134-1146. [PMID: 35075781 DOI: 10.1002/jbm.a.37361] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 12/25/2021] [Accepted: 01/05/2022] [Indexed: 12/14/2022]
Abstract
Implantation of a suitable nerve guide conduit (NGC) seeded with sufficient Schwann cells (SCs) is required to improve peripheral nerve regeneration efficiently. Given the limitations of isolating and culturing SCs, using various sources of stem cells, including mesenchymal stem cells (MSCs) obtained from nasal olfactory mucosa, can be desirable. Olfactory ecto-MSCs (OE-MSCs) are a new population of neural crest-derived stem cells that can proliferate and differentiate into SCs and can be considered a promising autologous alternative to produce SCs. Regardless, a biomimetic physicochemical microenvironment in NGC such as electroconductive substrate can affect the fate of transplanted stem cells, including differentiation toward SCs and nerve regeneration. Therefore, in this study, the effect of 3D printed polycaprolactone (PCL)/polypyrrole (PPy) conductive scaffolds on differentiation of human OE-MSCS into functional SC-like phenotypes was investigated. Biological evaluation of 3D printed scaffolds was examined by in vitro culturing the OE-MSCs on samples surfaces, and conductivity showed no effect on increased cell attachment, proliferation rate, viability, and distribution. In contrast, immunocytochemical staining and real-time polymerase chain reaction analysis indicated that 3D structures coated with PPy could provide a favorable microenvironment for OE-MSCs differentiation. In addition, it was found that differentiated OE-MSCs within PCL/PPy could secrete the highest amounts of nerve growth factor and brain-derived neurotrophic factor neurotrophic factors compared to pure PCL and 2D culture. After co-culturing with PC12 cells, a significant increase in neurite outgrowth on PCL/PPy conductive scaffold seeded with differentiated OE-MSCs. These findings indicated that 3D printed PCL/PPy conductive scaffold could support differentiation of OE-MSCs into SC-like phenotypes to promote neurite outgrowth, suggesting their potential for neural tissue engineering applications.
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Affiliation(s)
- Maedeh Entezari
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Masoud Mozafari
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
- ENT and Head & Neck Research Center and Department, The Five Senses Health Institute, school of medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mehrdad Bakhtiyari
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Moradi
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Zohreh Bagher
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
- ENT and Head & Neck Research Center and Department, The Five Senses Health Institute, school of medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mansoureh Soleimani
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
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19
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Bjørge IM, Correia CR, Mano JF. Hipster microcarriers: exploring geometrical and topographical cues of non-spherical microcarriers in biomedical applications. MATERIALS HORIZONS 2022; 9:908-933. [PMID: 34908074 DOI: 10.1039/d1mh01694f] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Structure and organisation are key aspects of the native tissue environment, which ultimately condition cell fate via a myriad of processes, including the activation of mechanotransduction pathways. By modulating the formation of integrin-mediated adhesions and consequently impacting cell contractility, engineered geometrical and topographical cues may be introduced to activate downstream signalling and ultimately control cell morphology, proliferation, and differentiation. Microcarriers appear as attractive vehicles for cell-based tissue engineering strategies aiming to modulate this 3D environment, but also as vehicles for cell-free applications, given the ease in tuning their chemical and physical properties. In this review, geometry and topography are highlighted as two preponderant features in actively regulating interactions between cells and the extracellular matrix. While most studies focus on the 2D environment, we focus on how the incorporation of these strategies in 3D systems could be beneficial. The techniques applied to design 3D microcarriers with unique geometries and surface topographical cues are covered, as well as specific tissue engineering approaches employing these microcarriers. In fact, successfully achieving a functional histoarchitecture may depend on a combination of fine-tuned geometrically shaped microcarriers presenting intricately tailored topographical cues. Lastly, we pinpoint microcarrier geometry as a key player in cell-free biomaterial-based strategies, and its impact on drug release kinetics, the production of steerable microcarriers to target tumour cells, and as protein or antibody biosensors.
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Affiliation(s)
- Isabel M Bjørge
- Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro, Aveiro, Portugal.
| | - Clara R Correia
- Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro, Aveiro, Portugal.
| | - João F Mano
- Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro, Aveiro, Portugal.
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20
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Drewry M, Dailey MT, Rothermund K, Backman C, Dahl KN, Syed-Picard FN. Promoting and Orienting Axon Extension Using Scaffold-Free Dental Pulp Stem Cell Sheets. ACS Biomater Sci Eng 2022; 8:814-825. [PMID: 34982537 PMCID: PMC9821555 DOI: 10.1021/acsbiomaterials.1c01517] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Current treatments of facial nerve injury result in poor functional outcomes due to slow and inefficient axon regeneration and aberrant reinnervation. To address these clinical challenges, bioactive scaffold-free cell sheets were engineered using neurotrophic dental pulp stem/progenitor cells (DPCs) and their aligned extracellular matrix (ECM). DPCs endogenously supply high levels of neurotrophic factors (NTFs), growth factors capable of stimulating axonal regeneration, and an aligned ECM provides guidance cues to direct axon extension. Human DPCs were grown on a substrate comprising parallel microgrooves, inducing the cells to align and deposit a linearly aligned, collagenous ECM. The resulting cell sheets were robust and could be easily removed from the underlying substrate. DPC sheets produced NTFs at levels previously shown capable of promoting axon regeneration, and, moreover, inducing DPC alignment increased the expression of select NTFs relative to unaligned controls. Furthermore, the aligned DPC sheets were able to stimulate functional neuritogenic effects in neuron-like cells in vitro. Neuronally differentiated neuroblastoma SH-SY5Y cells produced neurites that were significantly more oriented and less branched when cultured on aligned cell sheets relative to unaligned sheets. These data demonstrate that the linearly aligned DPC sheets can biomechanically support axon regeneration and improve axonal guidance which, when applied to a facial nerve injury, will result in more accurate reinnervation. The aligned DPC sheets generated here could be used in combination with commercially available nerve conduits to enhance their bioactivity or be formed into stand-alone scaffold-free nerve conduits capable of facilitating improved facial nerve recovery.
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Affiliation(s)
- Michelle
D. Drewry
- Department
of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
| | - Matthew T. Dailey
- Department
of Oral and Maxillofacial Surgery, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
| | - Kristi Rothermund
- Department
of Oral Biology and Center for Craniofacial Regeneration, School of
Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
| | - Charles Backman
- Department
of Chemical Engineering, College of Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States
| | - Kris N. Dahl
- Department
of Chemical Engineering, College of Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States,Department
of Biomedical Engineering, College of Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States,McGowan
Institute for Regenerative Medicine, Pittsburgh, Pennsylvania 15219, United States,Forensics, Thornton Tomasetti, New York, New York 10271, United States
| | - Fatima N. Syed-Picard
- Department
of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States,Department
of Oral Biology and Center for Craniofacial Regeneration, School of
Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States,McGowan
Institute for Regenerative Medicine, Pittsburgh, Pennsylvania 15219, United States,. Phone: 412-648-8824
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21
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Zhang C, Lü D, Zhang F, Wu Y, Zheng L, Zhang X, Li Z, Sun S, Long M. Gravity-Vector Induces Mechanical Remodeling of rMSCs via Combined Substrate Stiffness and Orientation. Front Bioeng Biotechnol 2022; 9:724101. [PMID: 35198547 PMCID: PMC8859489 DOI: 10.3389/fbioe.2021.724101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2021] [Accepted: 12/30/2021] [Indexed: 11/23/2022] Open
Abstract
Distinct physical factors originating from the cellular microenvironment are crucial to the biological homeostasis of stem cells. While substrate stiffness and orientation are known to regulate the mechanical remodeling and fate decision of mesenchymal stem cells (MSCs) separately, it remains unclear how the two factors are combined to manipulate their mechanical stability under gravity vector. Here we quantified these combined effects by placing rat MSCs onto stiffness-varied poly-dimethylsiloxane (PDMS) substrates in upward (180°), downward (0°), or edge-on (90°) orientation. Compared with those values onto glass coverslip, the nuclear longitudinal translocation, due to the density difference between the nucleus and the cytosol, was found to be lower at 0° for 24 h and higher at 90° for 24 and 72 h onto 2.5 MPa PDMS substrate. At 0°, the cell was mechanically supported by remarkably reduced actin and dramatically enhanced vimentin expression. At 90°, both enhanced actin and vimentin expression worked cooperatively to maintain cell stability. Specifically, perinuclear actin stress fibers with a large number, low anisotropy, and visible perinuclear vimentin cords were formed onto 2.5 MPa PDMS at 90° for 72 h, supporting the orientation difference in nuclear translocation and global cytoskeleton expression. This orientation dependence tended to disappear onto softer PDMS, presenting distinctive features in nuclear translocation and cytoskeletal structures. Moreover, cellular morphology and focal adhesion were mainly affected by substrate stiffness, yielding a time course of increased spreading area at 24 h but decreased area at 72 h with a decrease of stiffness. Mechanistically, the cell tended to be stabilized onto these PDMS substrates via β1 integrin–focal adhesion complexes–actin mechanosensitive axis. These results provided an insight in understanding the combination of substrate stiffness and orientation in defining the mechanical stability of rMSCs.
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Affiliation(s)
- Chen Zhang
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China
| | - Dongyuan Lü
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China
- School of Engineering Science, University of Chinese Academy of Sciences, Beijing, China
| | - Fan Zhang
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China
- School of Engineering Science, University of Chinese Academy of Sciences, Beijing, China
| | - Yi Wu
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China
- School of Engineering Science, University of Chinese Academy of Sciences, Beijing, China
| | - Lu Zheng
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China
- School of Engineering Science, University of Chinese Academy of Sciences, Beijing, China
| | - Xiaoyu Zhang
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China
- School of Engineering Science, University of Chinese Academy of Sciences, Beijing, China
| | - Zhan Li
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China
| | - Shujin Sun
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China
- School of Engineering Science, University of Chinese Academy of Sciences, Beijing, China
| | - Mian Long
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China
- School of Engineering Science, University of Chinese Academy of Sciences, Beijing, China
- *Correspondence: Mian Long,
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22
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Sun M, Liu Y, Jiao K, Jia W, Jiang K, Cheng Z, Liu G, Luo Y. A periodontal tissue regeneration strategy via biphasic release of zeolitic imidazolate framework-8 and FK506 using a uniaxial electrospun Janus nanofiber. J Mater Chem B 2022; 10:765-778. [PMID: 35040470 DOI: 10.1039/d1tb02174e] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Guided tissue regeneration (GTR) strategies are an effective approach to repair periodontal defects by using GTR membranes. However, commercial GTR membranes still have limitations in periodontal tissue regeneration owing to lack of antibacterial and osteogenic properties. The development of novel Janus nanofibers with biphasic release characteristics based on the therapeutic needs of GTR is essential to tackle this issue. Here, we developed a multifunctional Janus nanofiber via uniaxial electrospinning, with zeolitic imidazolate framework-8 nanoparticle (ZIF-8 NP) loading in the hydrophilic polyvinylpyrrolidone (PVP) part and FK506 embedding in the hydrophobic polycaprolactone (PCL) part. The release of Zn2+ conformed to the Ritger-Peppas kinetics which could effectively prevent bacterial infection, and the release profile of FK506 was fitted to a first-order equation which could provide persistent osteogenic stimulation for osteogenesis. The periodontal tissue regeneration data from a rat periodontitis model revealed that the multifunctional electrospun Janus nanofibers could be used as an effective bioplatform to restore alveolar bone impairment, compared with the control group. In summary, the Janus nanofibers with biphasic release characteristics quickly exert antibacterial function as well as continuously provide a microenvironment beneficial to the osteogenesis process, demonstrating its great potential for GTR treatment in dental clinic applications.
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Affiliation(s)
- Maolei Sun
- Department of Stomatology, The Second Hospital of Jilin University, Changchun 130041, P. R. China.
| | - Yun Liu
- Department of Stomatology, The Second Hospital of Jilin University, Changchun 130041, P. R. China.
| | - Kun Jiao
- Department of Stomatology, The Second Hospital of Jilin University, Changchun 130041, P. R. China.
| | - Wenyuan Jia
- Department of Orthopedics, The Second Hospital of Jilin University, Changchun 130041, P. R. China
| | - Kongzhao Jiang
- Department of Stomatology, The Second Hospital of Jilin University, Changchun 130041, P. R. China.
| | - Zhiqiang Cheng
- College of Resources and Environment, Jilin Agriculture University, Changchun 130118, P. R. China
| | - Guomin Liu
- Department of Orthopedics, The Second Hospital of Jilin University, Changchun 130041, P. R. China
| | - Yungang Luo
- Department of Stomatology, The Second Hospital of Jilin University, Changchun 130041, P. R. China.
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23
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Fukushima K, Matsuzaki K, Oji M, Higuchi Y, Watanabe G, Suzuki Y, Kikuchi M, Fujimura N, Shimokawa N, Ito H, Kato T, Kawaguchi S, Tanaka M. Anisotropic, Degradable Polymer Assemblies Driven by a Rigid Hydrogen-Bonding Motif That Induce Shape-Specific Cell Responses. Macromolecules 2021. [DOI: 10.1021/acs.macromol.1c01894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Kazuki Fukushima
- Department of Polymer Science and Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510, Japan
- Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
| | - Kodai Matsuzaki
- Department of Polymer Science and Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510, Japan
| | - Masashi Oji
- Department of Polymer Science and Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510, Japan
| | - Yuji Higuchi
- Institute for Solid State Physics, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8581, Japan
| | - Go Watanabe
- Department of Physics, School of Science, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0373, Japan
| | - Yuki Suzuki
- Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, 6-3 Aramaki-aza Aoba, Aoba-ku, Sendai 980-8578, Japan
| | - Moriya Kikuchi
- Department of Polymer Science and Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510, Japan
| | - Nozomi Fujimura
- Department of Polymer Science and Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510, Japan
| | - Naofumi Shimokawa
- School of Materials and Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa 923-1292, Japan
| | - Hiroaki Ito
- Department of Physics, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
| | - Takashi Kato
- Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
| | - Seigou Kawaguchi
- Department of Polymer Science and Engineering, Yamagata University, 4-3-16 Jonan, Yonezawa, Yamagata 992-8510, Japan
| | - Masaru Tanaka
- Institute for Materials Chemistry and Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan
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24
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Wang X, Nie Z, Chang J, Lu ML, Kang Y. Multiple channels with interconnected pores in a bioceramic scaffold promote bone tissue formation. Sci Rep 2021; 11:20447. [PMID: 34650074 PMCID: PMC8516977 DOI: 10.1038/s41598-021-00024-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 10/01/2021] [Indexed: 11/13/2022] Open
Abstract
Insufficient nutrition exchange and limited transportation of blood supply in a porous only scaffold often hinder bone formation, even though the porous scaffold is loaded with cells or growth factors. To overcome these issues, we developed a cell- and growth factor-free approach to induce bone formation in a critical-size bone defect by using an interconnected porous beta-tricalcium phosphate (β-TCP) scaffold with multiple channels. In vitro cell experimental results showed that multiple channels significantly promoted cell attachment and proliferation of human bone marrow mesenchymal stem cells, stimulated their alkaline phosphatase activity, and up-regulated the osteogenic gene expression. Multiple channels also considerably stimulated the expression of various mechanosensing markers of the cells, such as focal adhesion kinase, filamentous actin, and Yes-associated protein-1 at both static and dynamic culturing conditions. The in vivo bone defect implantation results demonstrated more bone formation inside multiple-channeled scaffolds compared to non-channeled scaffolds. Multiple channels prominently accelerated collagen type I, bone sialoprotein and osteocalcin protein expression. Fluorochrome images and angiogenic marker CD31 staining exhibited more mineral deposition and longer vasculature structures in multiple-channeled scaffolds, compared to non-channeled scaffolds. All the findings suggested that the creation of interconnected multiple channels in the porous β-TCP scaffold is a very promising approach to promote bone tissue regeneration.
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Affiliation(s)
- Xuesong Wang
- Department of Ocean and Mechanical Engineering, College of Engineering and Computer Science, Florida Atlantic University, Boca Raton, FL, 33431, USA
| | - Ziyan Nie
- Department of Ocean and Mechanical Engineering, College of Engineering and Computer Science, Florida Atlantic University, Boca Raton, FL, 33431, USA
| | - Jia Chang
- Department of Periodontology, University of Florida College of Dentistry, Gainesville, FL, 32610, USA
| | - Michael L Lu
- Department of Biomedical Science, College of Medicine, Florida Atlantic University, Boca Raton, FL, 33431, USA.,Department of Biological Science, Faculty of Integrative Biology Program, College of Science, Florida Atlantic University, Boca Raton, FL, 33431, USA
| | - Yunqing Kang
- Department of Ocean and Mechanical Engineering, College of Engineering and Computer Science, Florida Atlantic University, Boca Raton, FL, 33431, USA. .,Department of Biomedical Science, College of Medicine, Florida Atlantic University, Boca Raton, FL, 33431, USA. .,Department of Biological Science, Faculty of Integrative Biology Program, College of Science, Florida Atlantic University, Boca Raton, FL, 33431, USA.
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25
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Cui L, Yao Y, Yim EKF. The effects of surface topography modification on hydrogel properties. APL Bioeng 2021; 5:031509. [PMID: 34368603 PMCID: PMC8318605 DOI: 10.1063/5.0046076] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 06/21/2021] [Indexed: 12/23/2022] Open
Abstract
Hydrogel has been an attractive biomaterial for tissue engineering, drug delivery, wound healing, and contact lens materials, due to its outstanding properties, including high water content, transparency, biocompatibility, tissue mechanical matching, and low toxicity. As hydrogel commonly possesses high surface hydrophilicity, chemical modifications have been applied to achieve the optimal surface properties to improve the performance of hydrogels for specific applications. Ideally, the effects of surface modifications would be stable, and the modification would not affect the inherent hydrogel properties. In recent years, a new type of surface modification has been discovered to be able to alter hydrogel properties by physically patterning the hydrogel surfaces with topographies. Such physical patterning methods can also affect hydrogel surface chemical properties, such as protein adsorption, microbial adhesion, and cell response. This review will first summarize the works on developing hydrogel surface patterning methods. The influence of surface topography on interfacial energy and the subsequent effects on protein adsorption, microbial, and cell interactions with patterned hydrogel, with specific examples in biomedical applications, will be discussed. Finally, current problems and future challenges on topographical modification of hydrogels will also be discussed.
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Affiliation(s)
- Linan Cui
- Department of Chemical Engineering, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada
| | - Yuan Yao
- Department of Chemical Engineering, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada
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26
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Bioprintable Lung Extracellular Matrix Hydrogel Scaffolds for 3D Culture of Mesenchymal Stromal Cells. Polymers (Basel) 2021; 13:polym13142350. [PMID: 34301107 PMCID: PMC8309540 DOI: 10.3390/polym13142350] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 07/09/2021] [Accepted: 07/14/2021] [Indexed: 12/15/2022] Open
Abstract
Mesenchymal stromal cell (MSC)-based cell therapy in acute respiratory diseases is based on MSC secretion of paracrine factors. Several strategies have proposed to improve this are being explored including pre-conditioning the MSCs prior to administration. We here propose a strategy for improving the therapeutic efficacy of MSCs based on cell preconditioning by growing them in native extracellular matrix (ECM) derived from the lung. To this end, a bioink with tunable stiffness based on decellularized porcine lung ECM hydrogels was developed and characterized. The bioink was suitable for 3D culturing of lung-resident MSCs without the need for additional chemical or physical crosslinking. MSCs showed good viability, and contraction assays showed the existence of cell–matrix interactions in the bioprinted scaffolds. Adhesion capacity and length of the focal adhesions formed were increased for the cells cultured within the lung hydrogel scaffolds. Also, there was more than a 20-fold increase of the expression of the CXCR4 receptor in the 3D-cultured cells compared to the cells cultured in plastic. Secretion of cytokines when cultured in an in vitro model of lung injury showed a decreased secretion of pro-inflammatory mediators for the cells cultured in the 3D scaffolds. Moreover, the morphology of the harvested cells was markedly different with respect to conventionally (2D) cultured MSCs. In conclusion, the developed bioink can be used to bioprint structures aimed to improve preconditioning MSCs for therapeutic purposes.
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Oyama TG, Oyama K, Kimura A, Yoshida F, Ishida R, Yamazaki M, Miyoshi H, Taguchi M. Collagen hydrogels with controllable combined cues of elasticity and topography to regulate cellular processes. Biomed Mater 2021; 16. [PMID: 34030146 DOI: 10.1088/1748-605x/ac0452] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Accepted: 05/24/2021] [Indexed: 12/13/2022]
Abstract
The elasticity, topography, and chemical composition of cell culture substrates influence cell behavior. However, the cellular responses toin vivoextracellular matrix (ECM), a hydrogel of proteins (mainly collagen) and polysaccharides, remain unknown as there is no substrate that preserves the key features of native ECM. This study introduces novel collagen hydrogels that can combine elasticity, topography, and composition and reproduce the correlation between collagen concentration (C) and elastic modulus (E) in native ECM. A simple reagent-free method based on radiation-cross-linking altered ECM-derived collagen I and hydrolyzed collagen (gelatin or collagen peptide) solutions into hydrogels with tunable elastic moduli covering a broad range of soft tissues (E= 1-236 kPa) originating from the final collagen density in the hydrogels (C= 0.3%-14%) and precise microtopographies (⩾1 μm). The amino acid composition ratio was almost unchanged by this method, and the obtained collagen hydrogels maintained enzyme-mediated degradability. These collagen hydrogels enabled investigation of the responses of cell lines (fibroblasts, epithelial cells, and myoblasts) and primary cells (rat cardiomyocytes) to soft topographic cues such as thosein vivounder the positive correlation betweenCandE. These cells adhered directly to the collagen hydrogels and chose to stay atop or spontaneously migrate into them depending onE, that is, the density of the collagen network,C. We revealed that the cell morphology and actin cytoskeleton organization conformed to the topographic cues, even when they are as soft asin vivoECM. The stiffer microgrooves on collagen hydrogels aligned cells more effectively, except HeLa cells that underwent drastic changes in cell morphology. These collagen hydrogels may not only reducein vivoandin vitrocell behavioral disparity but also facilitate artificial ECM design to control cell function and fate for applications in tissue engineering and regenerative medicine.
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Affiliation(s)
- Tomoko G Oyama
- Quantum Beam Science Research Directorate, National Institutes for Quantum and Radiological Science and Technology (QST), 1233 Watanukimachi, Takasaki-shi, Gunma 370-1292, Japan
| | - Kotaro Oyama
- Quantum Beam Science Research Directorate, National Institutes for Quantum and Radiological Science and Technology (QST), 1233 Watanukimachi, Takasaki-shi, Gunma 370-1292, Japan.,PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan
| | - Atsushi Kimura
- Quantum Beam Science Research Directorate, National Institutes for Quantum and Radiological Science and Technology (QST), 1233 Watanukimachi, Takasaki-shi, Gunma 370-1292, Japan
| | - Fumiya Yoshida
- Quantum Beam Science Research Directorate, National Institutes for Quantum and Radiological Science and Technology (QST), 1233 Watanukimachi, Takasaki-shi, Gunma 370-1292, Japan.,Graduate School of Science and Technology, Gunma University, 1-5-1 Tenjin-cho, Kiryu-shi, Gunma 376-0052, Japan
| | - Ryo Ishida
- Graduate School of Systems Design, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji-shi, Tokyo 192-0397, Japan
| | - Masashi Yamazaki
- Graduate School of Systems Design, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji-shi, Tokyo 192-0397, Japan
| | - Hiromi Miyoshi
- Graduate School of Systems Design, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji-shi, Tokyo 192-0397, Japan
| | - Mitsumasa Taguchi
- Quantum Beam Science Research Directorate, National Institutes for Quantum and Radiological Science and Technology (QST), 1233 Watanukimachi, Takasaki-shi, Gunma 370-1292, Japan
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Monteiro NO, Fangueiro JF, Neves NM. Fabrication of biomimetic patterned PCL membranes mimicking the complexity of Rubus fruticosus leaves surface. Colloids Surf B Biointerfaces 2021; 206:111910. [PMID: 34147929 DOI: 10.1016/j.colsurfb.2021.111910] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 05/21/2021] [Accepted: 06/05/2021] [Indexed: 01/05/2023]
Abstract
The development of bioresponsive interfaces that can induce a beneficial impact on cell mechanisms, such as adhesion, proliferation, migration and differentiation are of utmost relevance in Tissue engineering (TE) approaches. The surface topography is a captivating property that contribute to interesting cell responses, being inspired by several cues found in nature. Therefore, the study herein presented reports the fabrication of a surface topography using the Rubus fruticosus leaf on spin casting polycaprolactone (PCL) membranes. The topography was replicated by replica molding rapid fabrication technique and nanoimprint lithography (NIL). The biomimetic patterned PCL membranes (bpM) were successfully produced revealing high detail due to the complexity of the leaf's surface ranging from the stroma structures to nerves structures. The thermal evaluation revealed a slight increase of crystallinity of the bpM compared with the other tested conditions. However, did not induce significant effects on the melting and recrystallization temperatures. The mechanical properties revealed that the young modulus increase from 3.2 MPa to 4.4 MPa during the imprinting process. However, bpM presents a lowest elongation capacity than bare membrane (bM) (1076 to 444 %, respectively) due to the heterogeneous thickness induced by the topography. The selected topography revealed to promote a positive bioresponse, depicted by the improvement of the cellular behaviour and different organization. This promising strategy revealed that circumventing the traditional topographies by nature mimetic topographies is fundamental for the development of innovative bioresponsive substrates that can tune cellular behaviour in TE strategies.
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Affiliation(s)
- N O Monteiro
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, Portugal
| | - J F Fangueiro
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, Portugal
| | - N M Neves
- 3B's Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017, Barco, Guimarães, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, Portugal.
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29
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Xie YH, Tang CQ, Huang ZZ, Zhou SC, Yang YW, Yin Z, Heng BC, Chen WS, Chen X, Shen WL. ECM remodeling in stem cell culture: a potential target for regulating stem cell function. TISSUE ENGINEERING PART B-REVIEWS 2021; 28:542-554. [PMID: 34082581 DOI: 10.1089/ten.teb.2021.0066] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Stem cells (SCs) hold great potential for regenerative medicine, tissue engineering and cell therapy. The clinical applications of SCs require both high quality and quantity of transplantable cells. However, during conventional in vitro expansion, SCs tend to lose properties that make them amenable for cell therapies. Extracellular matrix (ECM) serves an essential regulatory part in the growth, differentiation and homeostasis of all cells in vivo. when signals transmitted to cells, they do not respond passively. Many cell types can remodel pericellular matrix to meet their specific needs. This reciprocal cell-ECM interaction is crucial for the conservation of cell and tissue functions and homeostasis. In vitro ECM remodeling also plays a key role in regulating the lineage fate of SCs. A deeper understanding of in vitro ECM remodeling may provide new perspectives for the maintenance of SC function. In this review, we critically examined three ways that cells can be used to influence the pericellular matrix: (i) exerting tensile force on the ECM, (ii) secreting a variety of ECM proteins, and (iii) degrading the surrounding matrix, and its impact on SC lineage fate. Finally, we describe the deficiencies of current studies and what needs to be done next to further understand the role of ECM remodeling in ex vivo SC cultures.
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Affiliation(s)
- Yuan-Hao Xie
- Zhejiang University School of Medicine Second Affiliated Hospital, 89681, Department of Orthopedic Surgery, Hangzhou, Zhejiang, China;
| | - Chen-Qi Tang
- Zhejiang University School of Medicine Second Affiliated Hospital, 89681, Department of Orthopedic Surgery, Hangzhou, Zhejiang, China;
| | - Zi-Zhan Huang
- Zhejiang University School of Medicine Second Affiliated Hospital, 89681, Department of Orthopedic Surgery, Hangzhou, Zhejiang, China;
| | - Si-Cheng Zhou
- Zhejiang University School of Medicine Second Affiliated Hospital, 89681, Hangzhou, Zhejiang, China;
| | - Yu-Wei Yang
- Zhejiang University School of Medicine, 26441, Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Hangzhou, Zhejiang, China;
| | - Zi Yin
- Zhejiang University School of Medicine, 26441, Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Hangzhou, Zhejiang, China;
| | - Boon Chin Heng
- Peking University School of Stomatology, 159460, Beijing, Beijing, China;
| | - Wei-Shan Chen
- Zhejiang University School of Medicine Second Affiliated Hospital, 89681, Department of Orthopedic Surgery, Hangzhou, Zhejiang, China;
| | - Xiao Chen
- Zhejiang University School of Medicine, 26441, Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Hangzhou, Zhejiang, China;
| | - Wei-Liang Shen
- Zhejiang University School of Medicine Second Affiliated Hospital, 89681, Department of Orthopedic Surgery, Hangzhou, Zhejiang, China;
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30
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Ren C, Hao X, Wang L, Hu Y, Meng L, Zheng S, Ren F, Bu W, Wang H, Li D, Zhang K, Sun H. Metformin Carbon Dots for Promoting Periodontal Bone Regeneration via Activation of ERK/AMPK Pathway. Adv Healthc Mater 2021; 10:e2100196. [PMID: 33987977 DOI: 10.1002/adhm.202100196] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 04/15/2021] [Indexed: 12/14/2022]
Abstract
The osteogenic potential of mesenchymal stem cells (MSCs) is severely impaired under persistent inflammation of periodontitis. A highly efficient way to promote or rescue osteogenic potential of MSCs under inflammation remains an unmet goal. Herein, metformin carbon dots (MCDs) with excellent biocompatibility are prepared from metformin hydrochloride and citric acid via a hydrothermal method. The MCDs can more effectively enhance the alkaline phosphatase (ALP) activity, calcium deposition nodules formation, expression of osteogenic genes and proteins in rat bone marrow mesenchymal stem cells (rBMSCs) than metformin under both inflammatory and normal conditions. Moreover, a novel pathway of extracellular signal-regulated kinases (ERK)/AMP-activated protein kinase (AMPK) signaling is involved in the MCDs-induced osteogenesis. In periodontitis rats, MCDs can effectively regenerate the lost alveolar bone, but not the metformin. Taken together, MCDs can be the promising candidate nanomaterial for periodontitis treatment. This work may provide a new pharmacological target of ERK/AMPK pathway for treating bone loss and also give additional insights into developing nanodrugs from the numerous medications.
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Affiliation(s)
- Chunxia Ren
- Hospital of Stomatology Jilin University Changchun 130021 P. R. China
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling Hospital of Stomatology Jilin University Changchun 130021 P. R. China
| | - Xinqing Hao
- Hospital of Stomatology Jilin University Changchun 130021 P. R. China
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling Hospital of Stomatology Jilin University Changchun 130021 P. R. China
| | - Lu Wang
- Hospital of Stomatology Jilin University Changchun 130021 P. R. China
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling Hospital of Stomatology Jilin University Changchun 130021 P. R. China
| | - Yue Hu
- Hospital of Stomatology Jilin University Changchun 130021 P. R. China
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling Hospital of Stomatology Jilin University Changchun 130021 P. R. China
| | - Lin Meng
- Hospital of Stomatology Jilin University Changchun 130021 P. R. China
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling Hospital of Stomatology Jilin University Changchun 130021 P. R. China
| | - Shize Zheng
- Hospital of Stomatology Jilin University Changchun 130021 P. R. China
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling Hospital of Stomatology Jilin University Changchun 130021 P. R. China
| | - Feilong Ren
- Hospital of Stomatology Jilin University Changchun 130021 P. R. China
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling Hospital of Stomatology Jilin University Changchun 130021 P. R. China
| | - Wenhuan Bu
- School of Stomatology China Medical University Shenyang 110001 P. R. China
| | - Huan Wang
- State Key Laboratory of Rare Earth Resources Utilization Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun 130022 P. R. China
| | - Daowei Li
- Hospital of Stomatology Jilin University Changchun 130021 P. R. China
- Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling Hospital of Stomatology Jilin University Changchun 130021 P. R. China
| | - Kai Zhang
- State Key Laboratory of Supramolecular Structure and Materials College of Chemistry Jilin University Changchun 130012 P. R. China
| | - Hongchen Sun
- Hospital of Stomatology Jilin University Changchun 130021 P. R. China
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31
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Luo C, Lü D, Zheng L, Zhang F, Zhang X, Lü S, Zhang C, Jia X, Shu X, Li P, Li Z, Long M. Hepatic differentiation of human embryonic stem cells by coupling substrate stiffness and microtopography. Biomater Sci 2021; 9:3776-3790. [PMID: 33876166 DOI: 10.1039/d1bm00174d] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Mechanical or physical cues are associated with the growth and differentiation of embryonic stem cells (ESCs). While the substrate stiffness or topography independently affects the differentiation of ESCs, their cooperative regulation on lineage-specific differentiation remains largely unknown. Here, four topographical configurations on stiff or soft polyacrylamide hydrogel were combined to direct hepatic differentiation of human H1 cells via a four-stage protocol, and the coupled impacts of stiffness and topography were quantified at distinct stages. Data indicated that the substrate stiffness is dominant in stemness maintenance on stiff gel and hepatic differentiation on soft gel while substrate topography assists the differentiation of hepatocyte-like cells in positive correlation with the circularity of H1 clones initially formed on the substrate. The differentiated cells exhibited liver-specific functions such as maintaining the capacities of CYP450 metabolism, glycogen synthesis, ICG engulfment, and repairing liver injury in CCl4-treated mice. These results implied that the coupling of substrate stiffness and topography, combined with the biochemical signals, is favorable to improve the efficiency and functionality of hepatic differentiation of human ESCs.
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Affiliation(s)
- Chunhua Luo
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China.
| | - Dongyuan Lü
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China. and School of Engineering Science, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Lu Zheng
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China. and School of Engineering Science, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Fan Zhang
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China. and School of Engineering Science, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Xiao Zhang
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China. and School of Engineering Science, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Shouqin Lü
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China. and School of Engineering Science, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Chen Zhang
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China.
| | - Xiaohua Jia
- CAS Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China
| | - Xinyu Shu
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China. and School of Engineering Science, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Peiwen Li
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China.
| | - Zhan Li
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China.
| | - Mian Long
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory) and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China. and School of Engineering Science, University of Chinese Academy of Sciences, Beijing 100049, China
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32
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Li Y, Wang J, Zhong W. Regulation and mechanism of YAP/TAZ in the mechanical microenvironment of stem cells (Review). Mol Med Rep 2021; 24:506. [PMID: 33982785 PMCID: PMC8134874 DOI: 10.3892/mmr.2021.12145] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Accepted: 02/02/2021] [Indexed: 12/31/2022] Open
Abstract
Stem cells receive cues from their physical and mechanical microenvironment via mechanosensing and mechanotransduction. These cues affect proliferation, self‑renewal and differentiation into specific cell fates. A growing body of evidence suggests that yes‑associated protein (YAP) and transcriptional coactivator with PDZ‑binding motif (TAZ) mechanotransduction is key for driving stem cell behavior and regeneration via the Hippo and other signaling pathways. YAP/TAZ receive a range of physical cues, including extracellular matrix stiffness, cell geometry, flow shear stress and mechanical forces in the cytoskeleton, and translate them into cell‑specific transcriptional programs. However, the mechanism by which mechanical signals regulate YAP/TAZ activity in stem cells is not fully understand. The present review summarizes the current knowledge of the mechanisms involved in YAP/TAZ regulation on the physical and mechanical microenvironment, as well as its potential effects on stem cell differentiation.
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Affiliation(s)
- Ying Li
- Department of Orthopaedics Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Jinming Wang
- Department of Orthopaedics Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Weiliang Zhong
- Department of Orthopaedics Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
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33
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Prouvé E, Drouin B, Chevallier P, Rémy M, Durrieu MC, Laroche G. Evaluating Poly(Acrylamide-co-Acrylic Acid) Hydrogels Stress Relaxation to Direct the Osteogenic Differentiation of Mesenchymal Stem Cells. Macromol Biosci 2021; 21:e2100069. [PMID: 33870650 DOI: 10.1002/mabi.202100069] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 03/30/2021] [Indexed: 11/09/2022]
Abstract
The aim of this study is to investigate polyacrylamide-based hydrogels stress relaxation and the subsequent impact on the osteogenic differentiation of human mesenchymal stem cells (hMSCs). Different hydrogels are synthesized by varying the amount of cross-linker and the ratio between the monomers (acrylamide and acrylic acid), and characterized by compression tests. It has been found that hydrogels containing 18% of acrylic acid exhibit an average relaxation of 70%, while pure polyacrylamide gels show an average relaxation of 15%. Subsequently, hMSCs are cultured on two different hydrogels functionalized with a mimetic peptide of the bone morphogenetic protein-2 to enable cell adhesion and favor their osteogenic differentiation. Phalloidin staining shows that for a constant stiffness of 55 kPa, a hydrogel with a low relaxation (15%) leads to star-shaped cells, which is typical of osteocytes, while a hydrogel with a high relaxation (70%) presents cells with a polygonal shape characteristic of osteoblasts. Immunofluorescence labeling of E11, strongly expressed in early osteocytes, also shows a dramatically higher expression for cells cultured on the hydrogel with low relaxation (15%). These results clearly demonstrate that, by fine-tuning hydrogels stress relaxation, hMSCs differentiation can be directed toward osteoblasts, and even osteocytes, which is particularly rare in vitro.
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Affiliation(s)
- Emilie Prouvé
- Department of mining, metallurgy, and materials engineering, Surface Engineering Laboratory, Research Center on Advanced Materials, Laval University, 1065 Avenue de la médecine, Québec, G1V 0A6, Canada.,Research Center of the University Hospital of Québec, Regenerative Medicine axis, St-François d'Assise Hospital, Laval University, 10 rue de l'Espinay, Québec, G1L 3L5, Canada.,Institute of Chemistry and Biology of Membranes and Nano-objects (UMR 5248 CBMN), Bordeaux University, Allée Geoffroy St Hilaire - Bât B14, Pessac, 33600, France.,CNRS, CBMN UMR5248, Allée Geoffroy Saint Hilaire - Bât B14, Pessac, 33600, France.,Bordeaux INP, CBMN UMR5248, Allée Geoffroy Saint Hilaire - Bât B14, Pessac, 33600, France
| | - Bernard Drouin
- Research Center of the University Hospital of Québec, Regenerative Medicine axis, St-François d'Assise Hospital, Laval University, 10 rue de l'Espinay, Québec, G1L 3L5, Canada
| | - Pascale Chevallier
- Department of mining, metallurgy, and materials engineering, Surface Engineering Laboratory, Research Center on Advanced Materials, Laval University, 1065 Avenue de la médecine, Québec, G1V 0A6, Canada.,Research Center of the University Hospital of Québec, Regenerative Medicine axis, St-François d'Assise Hospital, Laval University, 10 rue de l'Espinay, Québec, G1L 3L5, Canada
| | - Murielle Rémy
- Institute of Chemistry and Biology of Membranes and Nano-objects (UMR 5248 CBMN), Bordeaux University, Allée Geoffroy St Hilaire - Bât B14, Pessac, 33600, France.,CNRS, CBMN UMR5248, Allée Geoffroy Saint Hilaire - Bât B14, Pessac, 33600, France.,Bordeaux INP, CBMN UMR5248, Allée Geoffroy Saint Hilaire - Bât B14, Pessac, 33600, France
| | - Marie-Christine Durrieu
- Institute of Chemistry and Biology of Membranes and Nano-objects (UMR 5248 CBMN), Bordeaux University, Allée Geoffroy St Hilaire - Bât B14, Pessac, 33600, France.,CNRS, CBMN UMR5248, Allée Geoffroy Saint Hilaire - Bât B14, Pessac, 33600, France.,Bordeaux INP, CBMN UMR5248, Allée Geoffroy Saint Hilaire - Bât B14, Pessac, 33600, France
| | - Gaétan Laroche
- Department of mining, metallurgy, and materials engineering, Surface Engineering Laboratory, Research Center on Advanced Materials, Laval University, 1065 Avenue de la médecine, Québec, G1V 0A6, Canada.,Research Center of the University Hospital of Québec, Regenerative Medicine axis, St-François d'Assise Hospital, Laval University, 10 rue de l'Espinay, Québec, G1L 3L5, Canada
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Li W, Li P, Li N, Du Y, Lü S, Elad D, Long M. Matrix stiffness and shear stresses modulate hepatocyte functions in a fibrotic liver sinusoidal model. Am J Physiol Gastrointest Liver Physiol 2021; 320:G272-G282. [PMID: 33296275 PMCID: PMC8609567 DOI: 10.1152/ajpgi.00379.2019] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Extracellular matrix (ECM) rigidity has important effects on cell behaviors and increases sharply in liver fibrosis and cirrhosis. Hepatic blood flow is essential in maintaining hepatocytes' (HCs) functions. However, it is still unclear how matrix stiffness and shear stresses orchestrate HC phenotype in concert. A fibrotic three-dimensional (3-D) liver sinusoidal model is constructed using a porous membrane sandwiched between two polydimethylsiloxane (PDMS) layers with respective flow channels. The HCs are cultured in collagen gels of various stiffnesses in the lower channel, whereas the upper channel is pre-seeded with liver sinusoidal endothelial cells (LSECs) and accessible to shear flow. The results reveal that HCs cultured within stiffer matrices exhibit reduced albumin production and cytochrome P450 (CYP450) reductase expression. Low shear stresses enhance synthetic and metabolic functions of HC, whereas high shear stresses lead to the loss of HC phenotype. Furthermore, both mechanical factors regulate HC functions by complementing each other. These observations are likely attributed to mechanically induced mass transport or key signaling molecule of hepatocyte nuclear factor 4α (HNF4α). The present study results provide an insight into understanding the mechanisms of HC dysfunction in liver fibrosis and cirrhosis, especially from the viewpoint of matrix stiffness and blood flow.NEW & NOTEWORTHY A fibrotic three-dimensional (3-D) liver sinusoidal model was constructed to mimic different stages of liver fibrosis in vivo and to explore the cooperative effects of matrix stiffness and shear stresses on hepatocyte (HC) functions. Mechanically induced alterations of mass transport mainly contributed to HC functions via typical mechanosensitive signaling.
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Affiliation(s)
- Wang Li
- 1Center for Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing, People’s Republic of China,2Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, People’s Republic of China,3Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, People’s Republic of China,4School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing, People’s Republic of China
| | - Peiwen Li
- 1Center for Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing, People’s Republic of China,2Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, People’s Republic of China,3Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, People’s Republic of China,4School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing, People’s Republic of China
| | - Ning Li
- 1Center for Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing, People’s Republic of China,2Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, People’s Republic of China,3Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, People’s Republic of China,4School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing, People’s Republic of China
| | - Yu Du
- 1Center for Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing, People’s Republic of China,2Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, People’s Republic of China,3Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, People’s Republic of China,4School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing, People’s Republic of China
| | - Shouqin Lü
- 1Center for Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing, People’s Republic of China,2Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, People’s Republic of China,3Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, People’s Republic of China,4School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing, People’s Republic of China
| | - David Elad
- 5Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel
| | - Mian Long
- 1Center for Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing, People’s Republic of China,2Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, People’s Republic of China,3Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, People’s Republic of China,4School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing, People’s Republic of China
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Kao TW, Chiou A, Lin KH, Liu YS, Lee OKS. Alteration of 3D Matrix Stiffness Regulates Viscoelasticity of Human Mesenchymal Stem Cells. Int J Mol Sci 2021; 22:ijms22052441. [PMID: 33670996 PMCID: PMC7957533 DOI: 10.3390/ijms22052441] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 02/23/2021] [Accepted: 02/25/2021] [Indexed: 12/13/2022] Open
Abstract
Human mesenchymal stem cells (hMSCs) possess potential of bone formation and were proposed as ideal material against osteoporosis. Although interrogation of directing effect on lineage specification by physical cues has been proposed, how mechanical stimulation impacts intracellular viscoelasticity during osteogenesis remained enigmatic. Cyto-friendly 3D matrix was prepared with polyacrylamide and conjugated fibronectin. The hMSCs were injected with fluorescent beads and chemically-induced toward osteogenesis. The mechanical properties were assessed using video particle tracking microrheology. Inverted epifluorescence microscope was exploited to capture the Brownian trajectory of hMSCs. Mean square displacement was calculated and transformed into intracellular viscoelasticity. Two different stiffness of microspheres (12 kPa, 1 kPa) were established. A total of 45 cells were assessed. hMSCs possessed equivalent mechanical traits initially in the first week, while cells cultured in rigid matrix displayed significant elevation over elastic (G′) and viscous moduli (G″) on day 7 (p < 0.01) and 14 (p < 0.01). However, after two weeks, soft niches no longer stiffened hMSCs, whereas the effect by rigid substrates was consistently during the entire differentiation course. Stiffness of matrix impacted the viscoelasticity of hMSCs. Detailed recognition of how microenvironment impacts mechanical properties and differentiation of hMSCs will facilitate the advancement of tissue engineering and regenerative medicine.
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Affiliation(s)
- Ting-Wei Kao
- Department of Medical Education, National Taiwan University Hospital, Taipei 100, Taiwan;
- Faculty of Medicine, National Yang-Ming University, Taipei 100, Taiwan
| | - Arthur Chiou
- Institute of Biophotonics, National Yang-Ming University, Taipei 112, Taiwan;
- Biophotonics and Molecular Imaging Research Center, National Yang-Ming University, Taipei 112, Taiwan
| | - Keng-Hui Lin
- Institute of Physics, Academia Sinica, Taipei 115, Taiwan;
| | - Yi-Shiuan Liu
- Department of Physiology and Pharmacology, Chang Gung University College of Medicine, Taoyuan 333, Taiwan;
- Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
- Institute of Clinical Medicine and Stem Cell Research Center, National Yang-Ming University, Taipei 115, Taiwan
| | - Oscar Kuang-Sheng Lee
- Institute of Clinical Medicine and Stem Cell Research Center, National Yang-Ming University, Taipei 115, Taiwan
- Department of Medical Research, Taipei Veterans General Hospital, Taipei 115, Taiwan
- Department of Orthopedics, School of Medicine, China Medical University, Taichung 404, Taiwan
- Department of Orthopedics, China Medical University Hospital, Taichung 404, Taiwan
- Correspondence:
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Yu S, Liu D, Wang T, Lee YZ, Wong JCN, Song X. Micropatterning of polymer substrates for cell culture. J Biomed Mater Res B Appl Biomater 2021; 109:1525-1533. [PMID: 33590658 DOI: 10.1002/jbm.b.34811] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 11/16/2020] [Accepted: 01/14/2021] [Indexed: 11/11/2022]
Abstract
The cell microenvironment such as substrate topology plays an important role in biological processes. In this study, microgrooves were successfully produced on surfaces of both thermoplastic and thermoset polymers using cost-effective techniques for mass production. The micropatterning of thermoplastic polystyrene (PS) petri dish was accomplished efficiently using an in-house developed low-cost hot embossing system. The high replication fidelity of the microgroove with depth and width of 2 μm and spacing of 2 μm was achieved by using silicone rubber as a soft counter mold. This patterned petri dish subsequently served as the cast to replicate the micropattern onto thermoset polydimethylsiloxane (PDMS). It was found that the micropattern increased the hydrophobicity of both PS and PDMS surfaces. The effect of the substrate micropattern on cellular behaviors was preliminarily investigated with untreated and treated PS petri dish as well as PDMS. The results show that the micropattern significantly improved cell adhesion and proliferation for cells cultured on untreated PS petri dish and PDMS substrates. Moreover, the micropattern induced obvious cell alignment along the microgrooves for culturing on all substrates which were studied.
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Affiliation(s)
- Suzhu Yu
- Polymer Processing Group, Singapore Institute of Manufacturing Technology, Singapore
| | - Dan Liu
- Polymer Processing Group, Singapore Institute of Manufacturing Technology, Singapore.,Biomanufacturing Technology Group 2, Bioprocessing Technology Institute, Singapore
| | - Tianyi Wang
- Polymer Processing Group, Singapore Institute of Manufacturing Technology, Singapore
| | - Yi Zhen Lee
- School of Materials Science and Engineering, Nanyang Technological University, Singapore
| | - Joshua Cheng Ning Wong
- Polymer Processing Group, Singapore Institute of Manufacturing Technology, Singapore.,Advanced Remanufacturing and Technology Centre, Singapore
| | - Xu Song
- Polymer Processing Group, Singapore Institute of Manufacturing Technology, Singapore.,Department of Mechanical and Automation Engineering, The Chinese University of Hong Kong
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Development and characterisation of cytocompatible polyester substrates with tunable mechanical properties and degradation rate. Acta Biomater 2021; 121:303-315. [PMID: 33227488 DOI: 10.1016/j.actbio.2020.11.026] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Revised: 11/12/2020] [Accepted: 11/17/2020] [Indexed: 12/18/2022]
Abstract
Although it has been repeatedly indicated the importance to develop implantable devices and cell culture substrates with tissue-specific rigidity, current commercially available products, in particular cell culture substrates, have rigidity values well above most tissues in the body. Herein, six resorbable polyester films were fabricated using compression moulding with a thermal presser into films with tailored stiffness by appropriately selecting the ratio of their building up monomers (e.g. lactide, glycolide, trimethylene carbonate, dioxanone, ε-caprolactone). Typical NMR and FTIR spectra were obtained, suggesting that the fabrication process did not have a negative effect on the conformation of the polymers. Surface roughness analysis revealed no apparent differences between the films as a function of polymer composition. Subject to polymer composition, polymeric films were obtained with glass transition temperatures from -52 °C to 61 °C; contact angles in water from 81 ° to 94 °; storage modulus from 108 MPa to 2,756 MPa and loss modulus from 8 MPa to 507 MPa (both in wet state, at 1 Hz frequency and at 37 °C); ultimate tensile strength from 8 MPa to 62 MPa, toughness from 23 MJ/m3 to 287 MJ/m3, strain at break from 3 % to 278 %, macro-scale Young's modulus from 110 MPa to 2,184 MPa (all in wet state); and nano-scale Young's modulus from 6 kPa to 15,019 kPa (in wet state). With respect to in vitro degradation in phosphate buffered saline at 37 °C, some polymeric films [e.g. poly(glycolide-lactide) 30 / 70] started degrading from day 7 (shortest timepoint assessed), whilst others [e.g. poly(glycolide-co-ε-caprolactone) 10 / 90] were more resilient to degradation up to day 21 (longest timepoint assessed). In vitro biological analysis using human dermal fibroblasts and a human monocyte cell line (THP-1) showed the potential of the polymeric films to support cell growth and controlled immune response. Evidently, the selected polymers exhibited properties suitable for a range of clinical indications.
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38
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Onfroy-Roy L, Hamel D, Foncy J, Malaquin L, Ferrand A. Extracellular Matrix Mechanical Properties and Regulation of the Intestinal Stem Cells: When Mechanics Control Fate. Cells 2020; 9:cells9122629. [PMID: 33297478 PMCID: PMC7762382 DOI: 10.3390/cells9122629] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 12/01/2020] [Accepted: 12/04/2020] [Indexed: 02/07/2023] Open
Abstract
Intestinal stem cells (ISC) are crucial players in colon epithelium physiology. The accurate control of their auto-renewal, proliferation and differentiation capacities provides a constant flow of regeneration, maintaining the epithelial intestinal barrier integrity. Under stress conditions, colon epithelium homeostasis in disrupted, evolving towards pathologies such as inflammatory bowel diseases or colorectal cancer. A specific environment, namely the ISC niche constituted by the surrounding mesenchymal stem cells, the factors they secrete and the extracellular matrix (ECM), tightly controls ISC homeostasis. Colon ECM exerts physical constraint on the enclosed stem cells through peculiar topography, stiffness and deformability. However, little is known on the molecular and cellular events involved in ECM regulation of the ISC phenotype and fate. To address this question, combining accurately reproduced colon ECM mechanical parameters to primary ISC cultures such as organoids is an appropriated approach. Here, we review colon ECM physical properties at physiological and pathological states and their bioengineered in vitro reproduction applications to ISC studies.
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Affiliation(s)
- Lauriane Onfroy-Roy
- IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, 31024 Toulouse, France;
- Correspondence: (L.O.-R.); (A.F.); Tel.: +33-5-62-744-522 (A.F.)
| | - Dimitri Hamel
- IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, 31024 Toulouse, France;
- LAAS-CNRS, Université de Toulouse, CNRS, 31400 Toulouse, France; (J.F.); (L.M.)
| | - Julie Foncy
- LAAS-CNRS, Université de Toulouse, CNRS, 31400 Toulouse, France; (J.F.); (L.M.)
| | - Laurent Malaquin
- LAAS-CNRS, Université de Toulouse, CNRS, 31400 Toulouse, France; (J.F.); (L.M.)
| | - Audrey Ferrand
- IRSD, Université de Toulouse, INSERM, INRA, ENVT, UPS, 31024 Toulouse, France;
- Correspondence: (L.O.-R.); (A.F.); Tel.: +33-5-62-744-522 (A.F.)
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Li P, Zhou J, Li W, Wu H, Hu J, Ding Q, Lü S, Pan J, Zhang C, Li N, Long M. Characterizing liver sinusoidal endothelial cell fenestrae on soft substrates upon AFM imaging and deep learning. Biochim Biophys Acta Gen Subj 2020; 1864:129702. [PMID: 32814074 DOI: 10.1016/j.bbagen.2020.129702] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 07/02/2020] [Accepted: 08/02/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Liver sinusoidal endothelial cells (LSECs) display unique fenestrated morphology. Alterations in the size and number of fenestrae play a crucial role in the progression of various liver diseases. While their features have been visualized using atomic force microscopy (AFM), the in situ imaging methods and off-line analyses are further required for fenestra quantification. METHODS Primary mouse LSECs were cultured on a collagen-I-coated culture dish, or a polydimethylsiloxane (PDMS) or polyacrylamide (PA) hydrogel substrate. An AFM contact mode was applied to visualize fenestrae on individual fixed LSECs. Collected images were analyzed using an in-house developed image recognition program based on fully convolutional networks (FCN). RESULTS Key scanning parameters were first optimized for visualizing the fenestrae on LSECs on culture dish, which was also applicable for the LSECs cultured on various hydrogels. The intermediate-magnification morphology images of LSECs were used for developing the FCN-based, fenestra recognition program. This program enabled us to recognize the vast majority of fenestrae from AFM images after twice trainings at a typical accuracy of 81.6% on soft substrate and also quantify the statistics of porosity, number of fenestrae and distribution of fenestra diameter. CONCLUSIONS Combining AFM imaging with FCN training is able to quantify the morphological distributions of LSEC fenestrae on various substrates. SIGNIFICANCE AFM images acquired and analyzed here provided the global information of surface ultramicroscopic structures over an entire cell, which is fundamental in understanding their regulatory mechanisms and pathophysiological relevance in fenestra-like evolution of individual cells on stiffness-varied substrates.
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Affiliation(s)
- Peiwen Li
- School of Life Science, Beijing Institute of Technology, Beijing 10081, China; Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China
| | - Jin Zhou
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China
| | - Wang Li
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China; School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Huan Wu
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China; Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Chongqing 400044, China
| | - Jinrong Hu
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China
| | - Qihan Ding
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China; School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Shouqin Lü
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China; School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Jun Pan
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Chongqing 400044, China
| | - Chunyu Zhang
- School of Life Science, Beijing Institute of Technology, Beijing 10081, China.
| | - Ning Li
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China; School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
| | - Mian Long
- Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China; School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
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40
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Huang X, Yang X, Sun C, Huang S, Cheng M, Han Y. Biophysical signal transduction in cancer cells: Understanding its role in cancer pathogenesis and treatment. Biochim Biophys Acta Rev Cancer 2020; 1874:188402. [PMID: 32771535 DOI: 10.1016/j.bbcan.2020.188402] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 07/21/2020] [Accepted: 07/21/2020] [Indexed: 12/12/2022]
Abstract
Signaling between cells can promote both the development and progression of cancer. It has been found that chemical and physical signals, together with extracellular factors, can influence cancer progression. In this review, we focus on the physical microenvironment of cancer cells and examine the action of mechanical, electromagnetic, thermal, and acoustic signals on cancer cells, which may provide new directions for cancer research and treatment.
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Affiliation(s)
- XiaoLei Huang
- School of Life Science and Technology, Weifang Medical University, Weifang, Shandong 261053, PR China
| | - XiaoXu Yang
- School of Life Science and Technology, Weifang Medical University, Weifang, Shandong 261053, PR China
| | - Chenchen Sun
- School of Life Science and Technology, Weifang Medical University, Weifang, Shandong 261053, PR China
| | - ShuXia Huang
- Department of Psychology, Weifang Medical University, Weifang, Shandong 261053, PR China
| | - Min Cheng
- Department of Physiology, Weifang Medical University, Weifang, Shandong 261053, PR China
| | - Yangyang Han
- School of Life Science and Technology, Weifang Medical University, Weifang, Shandong 261053, PR China.
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41
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Biomimetic bone regeneration using angle-ply collagen membrane-supported cell sheets subjected to mechanical conditioning. Acta Biomater 2020; 112:75-86. [PMID: 32505802 DOI: 10.1016/j.actbio.2020.05.041] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 05/28/2020] [Accepted: 05/28/2020] [Indexed: 02/07/2023]
Abstract
Bone injuries are common and new strategies are desired for achieving ideal bone regeneration for bone defect repair. Scaffolds with bone-mimicking characteristics may provide an appropriate microenvironment to promote bone regeneration. Meanwhile, mechanical stimulation effectively regulates a wide range of cellular behaviors such as cell proliferation and differentiation. In this study, biomimetic multi-layer cell-collagen constructs with angle-ply structural feature were prepared by assembling micropatterned collagen membranes on which aligned MC3T3-E1 cells were cultured. The anisotropic microgrooved collagen membranes effectively guided the alignment of cells and promoted the osteogenic differentiation of them. To further promote cell differentiation and extracellular matrix production, the multi-layer cell-collagen constructs were cultured under mechanical conditioning through cyclic stretching. It was found that the constructs with both cell alignment and mechanical conditioning resulted in better osteogenic potential than those with cell alignment or mechanical conditioning alone. Upon implantation into the critical-sized calvarial defects of mice, the constructs with both cell alignment and mechanical conditioning achieved best new bone formation efficacy. Together, findings from this study reveal that synergized use of microstructural and mechanical cues may provide an effective new approach toward bone regeneration. STATEMENT OF SIGNIFICANCE: Biomimicking is an effective strategy to promote bone regeneration for repairing bone defects. Although numerous studies which micro-structurally mimicked native bone using various scaffolds, far less studies have paid attention to the mechanical environment of bone. In this study, angle-ply collagen membrane-supported cell sheets were prepared and pre-conditioned using mechanical loading prior to implantation at bone defects. The constructs with cell alignment and subjected to mechanical conditioning resulted in better osteogenic differentiation of cells in vitro and new bone formation in vivo than those with cell alignment or mechanical conditioning alone. Therefore, recapitulation of both microstructural and mechanical features of native bone may result in a synergistic effect and provides an effective approach toward bone regeneration.
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Rahmati M, Silva EA, Reseland JE, A Heyward C, Haugen HJ. Biological responses to physicochemical properties of biomaterial surface. Chem Soc Rev 2020; 49:5178-5224. [PMID: 32642749 DOI: 10.1039/d0cs00103a] [Citation(s) in RCA: 163] [Impact Index Per Article: 32.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Biomedical scientists use chemistry-driven processes found in nature as an inspiration to design biomaterials as promising diagnostic tools, therapeutic solutions, or tissue substitutes. While substantial consideration is devoted to the design and validation of biomaterials, the nature of their interactions with the surrounding biological microenvironment is commonly neglected. This gap of knowledge could be owing to our poor understanding of biochemical signaling pathways, lack of reliable techniques for designing biomaterials with optimal physicochemical properties, and/or poor stability of biomaterial properties after implantation. The success of host responses to biomaterials, known as biocompatibility, depends on chemical principles as the root of both cell signaling pathways in the body and how the biomaterial surface is designed. Most of the current review papers have discussed chemical engineering and biological principles of designing biomaterials as separate topics, which has resulted in neglecting the main role of chemistry in this field. In this review, we discuss biocompatibility in the context of chemistry, what it is and how to assess it, while describing contributions from both biochemical cues and biomaterials as well as the means of harmonizing them. We address both biochemical signal-transduction pathways and engineering principles of designing a biomaterial with an emphasis on its surface physicochemistry. As we aim to show the role of chemistry in the crosstalk between the surface physicochemical properties and body responses, we concisely highlight the main biochemical signal-transduction pathways involved in the biocompatibility complex. Finally, we discuss the progress and challenges associated with the current strategies used for improving the chemical and physical interactions between cells and biomaterial surface.
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Affiliation(s)
- Maryam Rahmati
- Department of Biomaterials, Institute of Clinical Dentistry, University of Oslo, 0317 Oslo, Norway. h.j.haugen.odont.uio.no
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Su X, Jing H, Yu W, Lei F, Wang R, Hu C, Li M, Lin T, Zhou H, Wang F, Liao L. A bone matrix-simulating scaffold to alleviate replicative senescence of mesenchymal stem cells during long-term expansion. J Biomed Mater Res A 2020; 108:1955-1967. [PMID: 32323459 DOI: 10.1002/jbm.a.36958] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 04/15/2020] [Accepted: 04/19/2020] [Indexed: 02/05/2023]
Abstract
Replicative senescence during in vitro augmentation, which is mostly induced by the loss of physiological microenvironment, hinders the application of mesenchymal stem cells (MSCs) in the clinic. Here, we investigated whether MSCs senescence could be prevented by bio-scaffold mimicking the natural tissue matrix. Human umbilical cord mesenchymal stem cells (hUCMSCs) exhibited a senescent phenotype during a long-term passage in the conventional culture dish. To fabricate the bone matrix, a naturally based matrix composed of nano-hydroxyapatite/chitosan/poly lactide-co-glycolide (nHA/CS/PLGA) was produced. Long-term passage resulted in an obvious increase in the expression of senescence markers and a reduction in the expression of master genes involved in tissue regeneration. Functional assay confirmed that nHA/CS/PLGA scaffold preserved the proliferation and differentiation of hUCMSCs even after being passaged 27 times. Moreover, in vivo ectopic bone formation assay revealed that the bone formation of hUCMSCs cultured on the nano-scaffolds for the long term was as robust as the cells in the early passage. In summary, our results demonstrate that nHA/CS/PLGA scaffold effectively preserves the stemness and youth of hUCMSCs in the long-term passage. Taken advantage of its compatibility and bioactivity, nHA/CS/PLGA scaffold is of great potential in large-scale expansion of MSCs for stem cell therapy and tissue engineering.
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Affiliation(s)
- Xiaoxia Su
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, China
| | - Huan Jing
- Department of Stomatology, Bethune International Peace Hospital, Shijiazhuang, China
| | - Wenting Yu
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, China
| | - Fengzhen Lei
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, China
| | - Rui Wang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, China
| | - Cheng Hu
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, China
| | - Mujia Li
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, China
| | - Tingting Lin
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, China
| | - Hong Zhou
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, China
| | - Fei Wang
- Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, China
| | - Li Liao
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China.,State Key Laboratory of Oral Disease, West China School of Stomatology, Sichuan University, Chengdu, China
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Zhou N, Ma X, Bernaerts KV, Ren P, Hu W, Zhang T. Expansion of Ovarian Cancer Stem-like Cells in Poly(ethylene glycol)-Cross-Linked Poly(methyl vinyl ether-alt-maleic acid) and Alginate Double-Network Hydrogels. ACS Biomater Sci Eng 2020; 6:3310-3326. [DOI: 10.1021/acsbiomaterials.9b01967] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Naizhen Zhou
- State Key Lab of Bioelectronics, National Demonstration Center for Experimental Biomedical Engineering Education, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
| | - Xiaoe Ma
- State Key Lab of Bioelectronics, National Demonstration Center for Experimental Biomedical Engineering Education, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
| | - Katrien V. Bernaerts
- Aachen-Maastricht Institute for Biobased Materials (AMIBM), Faculty of Science and Engineering, Maastricht University, Brightlands Chemelot Campus, Urmonderbaan 22, 6167 RD Geleen, The Netherlands
| | - Pengfei Ren
- State Key Lab of Bioelectronics, National Demonstration Center for Experimental Biomedical Engineering Education, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
| | - Wanjun Hu
- State Key Lab of Bioelectronics, National Demonstration Center for Experimental Biomedical Engineering Education, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
| | - Tianzhu Zhang
- State Key Lab of Bioelectronics, National Demonstration Center for Experimental Biomedical Engineering Education, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China
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Huang CC, Ravindran S, Kang M, Cooper LF, George A. Engineering a Self-Assembling Leucine Zipper Hydrogel System with Function-Specific Motifs for Tissue Regeneration. ACS Biomater Sci Eng 2020; 6:2913-2928. [PMID: 33463282 DOI: 10.1021/acsbiomaterials.0c00026] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Protein-based self-assembling hydrogels can exhibit remarkably tunable properties as a scaffold for regenerative medicine applications. In this study, we sought to develop a leucine zipper (LZ) based self-assembling hydrogel with function-specific motifs for tissue-specific regeneration. As a proof-of-concept approach, we incorporated (a) calcium-binding domains ESQES and QESQSEQS derived from dentin matrix protein 1 (DMP1) and (b) an heparin-binding domain adjacent preceded by an MMP2 (matrix metalloprotease 2) cleavage site to facilitate loading of heparin binding growth factors, such as BMP-2, VEGF, and TGF-β1, and their release in vivo by endogenous MMP2 proteolytic cleavage. These scaffolds were characterized and evaluated in vitro and in vivo. In vivo studies highlighted the potential of the engineered LZ hydrogel with respect to osteogenic differentiation of stem cells. The premineralized LZ scaffold loaded with HMSCs showed an enhanced osteoinductive property when compared with the control nonmineralized scaffold. The LZ backbone with heparin-binding domain containing an MMP2 cleavage site facilitated tethering of heparin-binding growth factors, such as VEGF, TGF-β1 and BMP2 and demonstrated controlled release of these active growth factor both in vitro and in vivo and demonstrated growth factor specific activity in vivo (BMP-2 and TGF-β1). Overall, we present a versatile protein based self-assembling system with tunable properties for tissue regeneration.
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Affiliation(s)
- Chun-Chieh Huang
- Brodie Tooth Development Genetics & Regenerative Medicine Research Laboratory Department of Oral Biology, University of Illinois at Chicago, 801 South Paulina Street, Room 561C, Chicago, Illinois 60612, United States
| | - Sriram Ravindran
- Brodie Tooth Development Genetics & Regenerative Medicine Research Laboratory Department of Oral Biology, University of Illinois at Chicago, 801 South Paulina Street, Room 561C, Chicago, Illinois 60612, United States
| | - Miya Kang
- Brodie Tooth Development Genetics & Regenerative Medicine Research Laboratory Department of Oral Biology, University of Illinois at Chicago, 801 South Paulina Street, Room 561C, Chicago, Illinois 60612, United States
| | - Lyndon F Cooper
- Brodie Tooth Development Genetics & Regenerative Medicine Research Laboratory Department of Oral Biology, University of Illinois at Chicago, 801 South Paulina Street, Room 561C, Chicago, Illinois 60612, United States
| | - Anne George
- Brodie Tooth Development Genetics & Regenerative Medicine Research Laboratory Department of Oral Biology, University of Illinois at Chicago, 801 South Paulina Street, Room 561C, Chicago, Illinois 60612, United States
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Comelles J, Fernández-Majada V, Berlanga-Navarro N, Acevedo V, Paszkowska K, Martínez E. Microfabrication of poly(acrylamide) hydrogels with independently controlled topography and stiffness. Biofabrication 2020; 12:025023. [PMID: 32050182 DOI: 10.1088/1758-5090/ab7552] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The stiffness and topography of a cell's extracellular matrix (ECM) are physical cues that play a key role in regulating processes that determine cellular fate and function. While substrate stiffness can dictate cell differentiation lineage, migration, and self-organization, topographical features can change the cell's differentiation profile or migration ability. Although both physical cues are present and intrinsic to the native tissues in vivo, in vitro studies have been hampered by the lack of technological set-ups that would be compatible with cell culture and characterization. In vitro studies therefore either focused on screening stiffness effects in cells cultured on flat substrates or on determining topography effects in cells cultured onto hard materials. Here, we present a reliable, microfabrication method to obtain well defined topographical structures of micrometer size (5-10 μm) on soft polyacrylamide hydrogels with tunable mechanical stiffness (3-145 kPa) that closely mimic the in vivo situation. Topographically microstructured polyacrylamide hydrogels are polymerized by capillary force lithography using flexible materials as molds. The topographical microstructures are resistant to swelling, can be conformally functionalized by ECM proteins and sustain the growth of cell lines (fibroblasts and myoblasts) and primary cells (mouse intestinal epithelial cells). Our method can independently control stiffness and topography, which allows to individually assess the contribution of each physical cue to cell response or to explore potential synergistic effects. We anticipate that our fabrication method will be of great utility in tissue engineering and biophysics, especially for applications where the use of complex in vivo-like environments is of paramount importance.
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Affiliation(s)
- Jordi Comelles
- Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), c/Baldiri Reixac 10-12, E-08028, Barcelona, Spain
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Bai M, Cai L, Li X, Ye L, Xie J. Stiffness and topography of biomaterials dictate cell-matrix interaction in musculoskeletal cells at the bio-interface: A concise progress review. J Biomed Mater Res B Appl Biomater 2020; 108:2426-2440. [PMID: 32027091 DOI: 10.1002/jbm.b.34575] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2019] [Revised: 12/30/2019] [Accepted: 01/19/2020] [Indexed: 02/05/2023]
Abstract
Mutually interacted musculoskeletal tissues work together within the physiological environment full of varieties of external stimulus. Consistent with the locomotive function of the tissues, musculoskeletal cells are remarkably mechanosensitive to the physical cues. Signals like extracellular matrix (ECM) stiffness, topography, and geometry can be sensed and transduced into intracellular signaling cascades to trigger a series of cell responses, including cell adhesion, cell phenotype maintenance, cytoskeletal reconstruction, and stem cell differentiation (Du et al., 2011; Murphy et al., 2014; Lv et al., 2015; Kim et al., 2016; Kumar et al., 2017). With the development of tissue engineering and regenerative medicine, the potent effects of ECM physical properties on cell behaviors at the cell-matrix interface are drawing much attention. To mimic the interaction between cell and its ECM physical properties, developing advanced biomaterials with desired characteristics which could achieve the biointerface between cells and the surrounded matrix close to the physiological conditions becomes a great hotspot. In this review, based on the current publications in the field of biointerfaces, we systematically summarized the significant roles of stiffness and topography on musculoskeletal cell behaviors. We hope to shed light on the importance of physical cues in musculoskeletal tissue engineering and provide up to date strategies towards the natural or artificial replication of physiological microenvironment.
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Affiliation(s)
- Mingru Bai
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Linyi Cai
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xin Li
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Ling Ye
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Jing Xie
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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Doolin MT, Stroka KM. Integration of Mesenchymal Stem Cells into a Novel Micropillar Confinement Assay. Tissue Eng Part C Methods 2019; 25:662-676. [PMID: 31347455 PMCID: PMC6998058 DOI: 10.1089/ten.tec.2019.0083] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Accepted: 07/24/2019] [Indexed: 01/12/2023] Open
Abstract
Mechanical cues such as stiffness have been shown to influence cell gene expression, protein expression, and cell behaviors critical for tissue engineering. The mechanical cue of confinement is also a pervasive parameter affecting cells in vivo and in tissue-engineered constructs. Despite its prevalence, the mechanical cue of confinement lacks assays that provide precise control over the degree of confinement induced on cells, yield a large sample size, enable long-term culture, and enable easy visualization of cells over time. In this study, we developed a process to systematically confine cells using micropillar arrays. Using photolithography and polydimethylsiloxane (PDMS) molding, we created PDMS arrays of micropillars that were 5, 10, 20, or 50 μm in spacing and between 13 and 17 μm in height. The tops of micropillars were coated with Pluronic F127 to inhibit cell adhesion, and we observed that mesenchymal stem cells (MSCs) robustly infiltrated into the micropillar arrays. MSC and nucleus morphology were altered by narrowing the micropillar spacing, and cytoskeletal elements within MSCs appeared to become more diffuse with increasing confinement. Specifically, MSCs exhibited a ring of actin around their periphery and punctate focal adhesions. MSC migration speed was reduced by narrowing micropillar spacing, and distinct migration behaviors of MSCs emerged in the presence of micropillars. MSCs continued to proliferate within micropillar arrays after 3 weeks in culture, displaying our assay's capability for long-term studies. Our assay also has the capacity to provide adequate cell numbers for quantitative assays to investigate the effect of confinement on gene and protein expression. Through deeper understanding of cell mechanotransduction in the context of confinement, we can modify tissue-engineered constructs to be optimal for a given purpose. Impact Statement In this study, we developed a novel process to systematically confine cells using micropillar arrays. Our assay provides insight into cell behavior in response to mechanical confinement. Through deeper understanding of how cells sense and respond to confinement, we can fine tune tissue-engineered constructs to be optimal for a given purpose. By combining confinement with other physical cues, we can harness mechanical properties to encourage or inhibit cell migration, direct cells down a particular lineage, induce cell secretion of specific cytokines or extracellular vesicles, and ultimately direct cells to behave in a way conducive to tissue engineering.
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Affiliation(s)
- Mary T. Doolin
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland
| | - Kimberly M. Stroka
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland
- Biophysics Program, University of Maryland, College Park, Maryland
- Center for Stem Cell Biology and Regenerative Medicine, University of Maryland, Baltimore, Maryland
- Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, Maryland
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Jahanmard F, Baghban Eslaminejad M, Amani-Tehran M, Zarei F, Rezaei N, Croes M, Amin Yavari S. Incorporation of F-MWCNTs into electrospun nanofibers regulates osteogenesis through stiffness and nanotopography. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2019; 106:110163. [PMID: 31753334 DOI: 10.1016/j.msec.2019.110163] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Revised: 08/16/2019] [Accepted: 09/04/2019] [Indexed: 10/26/2022]
Abstract
Nanotopography and stiffness are major physical cues affecting cell fate. However, the current nanofiber modifications techniques are limited by their ability to control these two physical cues irrespective of each other without changing the materials' surface chemistry. For this reason, the isolated effects of topography and stiffness on osteogenic regulation in electrospun nanofibers have been studied incompletely. Here, we investigated 1. how functionalized multiwall carbon nanotubes (F-MWCNTs) loaded in Polycaprolactone (PCL) nanofibers control their physical properties and 2. whether the resulting unique structures lead to distinctive phenotypes in bone progenitor cells. Changes in material properties were measured by high-resolution electron microscopes, protein adsorption and tensile tests. The effect of the developed structures on human mesenchymal stem cell (MSC) osteogenic differentiation was determined by extensive quantification of early and late osteogenic marker genes. It was found that F-MWCNT loading was an effective method to independently control the PCL nanofiber surface nanoroughness or stiffness, depending on the applied F-MWCNT concentration. Collectively, this suggests that stiffness and topography activate distinct osteogenic signaling pathway. The current strategy can help our further understanding of the mechano-biological responses in osteoprogenitor cells, which could ultimately lead to improved design of bone substitute biomaterials.
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Affiliation(s)
- Fatemeh Jahanmard
- Department of Orthopedics, University Medical Centre Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands; Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, P.O. Box: 16635-148, Tehran, Iran; Nanotechnology Institute, Amirkabir University of Technology, P.O. Box: 15875-4413, Tehran, Iran.
| | - Mohamadreza Baghban Eslaminejad
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, P.O. Box: 16635-148, Tehran, Iran.
| | - Mohammad Amani-Tehran
- Department of Textile Engineering, Amirkabir University of Technology, P.O. Box: 15875-4413, Tehran, Iran
| | - Fatemeh Zarei
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, P.O. Box: 16635-148, Tehran, Iran
| | - Naeimeh Rezaei
- Department of Cell and Molecular Biology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran
| | - Michiel Croes
- Department of Orthopedics, University Medical Centre Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands
| | - Saber Amin Yavari
- Department of Orthopedics, University Medical Centre Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands
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50
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Li M, Fu X, Gao H, Ji Y, Li J, Wang Y. Regulation of an osteon-like concentric microgrooved surface on osteogenesis and osteoclastogenesis. Biomaterials 2019; 216:119269. [DOI: 10.1016/j.biomaterials.2019.119269] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 06/04/2019] [Accepted: 06/08/2019] [Indexed: 12/22/2022]
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