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Lee SH, Li Z, Zhang EY, Kim DH, Huang Z, Heo Y, Lee SJ, Kang HW, Burdick JA, Mauck RL, Heo SC. Precision repair of zone-specific meniscal injuries using a tunable extracellular matrix-based hydrogel system. Bioact Mater 2025; 48:400-413. [PMID: 40083776 PMCID: PMC11904587 DOI: 10.1016/j.bioactmat.2025.02.013] [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: 11/01/2024] [Revised: 02/06/2025] [Accepted: 02/06/2025] [Indexed: 03/16/2025] Open
Abstract
Meniscus injuries present significant therapeutic challenges due to their limited self-healing capacity and the diverse biological and mechanical properties across the tissue. Conventional repair strategies do not replicate the complex zonal characteristics within the meniscus, resulting in suboptimal outcomes. In this study, we introduce an innovative fetal/adult and stiffness-tunable meniscus decellularized extracellular matrix (DEM)-based hydrogel system designed for precision repair of heterogeneous, zonal-dependent meniscus injuries. By synthesizing fetal and adult DEM hydrogels, we identified distinct cellular responses, including that hydrogels with adult meniscus-derived DEM promote more fibrochondrogenic phenotypes. The incorporation of methacrylated hyaluronic acid (MeHA) further refined the mechanical properties and injectability of the DEM-based hydrogels. The combination of fetal and adult DEM with MeHA allowed for precise tuning of stiffness, influencing cell differentiation and closely mimicking native tissue environments. In vivo tests confirmed the biocompatibility of hydrogels and their integration with native meniscus tissues. Furthermore, advanced 3D bioprinting techniques enabled the fabrication of hybrid hydrogels with biomaterial and mechanical gradients, effectively emulating the zonal properties of meniscus tissue and enhancing cell integration. This study represents a significant advance in meniscus tissue engineering, providing a promising platform for customized regenerative therapies across a range of heterogeneous fibrous connective tissues.
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Affiliation(s)
- Se-Hwan Lee
- McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, United States
- Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan, 44919, Republic of Korea
| | - Zizhao Li
- McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, United States
- Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, 19104, United States
| | - Ellen Y. Zhang
- McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, United States
- Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, 19104, United States
| | - Dong Hwa Kim
- McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, United States
| | - Ziqi Huang
- Biofunctional Materials, Division of Applied Oral Sciences and Community Dental Care, Faculty of Dentistry, The University of Hong Kong, 34 Hospital Road, Sai Ying Pun, Hong Kong SAR, PR China
| | - Yuna Heo
- McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, United States
| | - Sang Jin Lee
- Biofunctional Materials, Division of Applied Oral Sciences and Community Dental Care, Faculty of Dentistry, The University of Hong Kong, 34 Hospital Road, Sai Ying Pun, Hong Kong SAR, PR China
| | - Hyun-Wook Kang
- Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan, 44919, Republic of Korea
| | - Jason A. Burdick
- Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, 19104, United States
- BioFrontiers Institute and Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO, 80309, United States
| | - Robert L. Mauck
- McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, United States
- Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, 19104, United States
- Translational Musculoskeletal Research Center, Corporal Michael J Crescenz VA Medical Center, Philadelphia, PA, 19104, United States
| | - Su Chin Heo
- McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, United States
- Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, 19104, United States
- Translational Musculoskeletal Research Center, Corporal Michael J Crescenz VA Medical Center, Philadelphia, PA, 19104, United States
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Huang H, Xiao L, Fang L, Lei M, Liu Z, Gao S, Lei Q, Lei J, Wei R, Lei Y, Xue L, Geng Z, Cai L, Yan F. Static Topographical Cue Combined with Dynamic Fluid Stimulation Enhances the Macrophage Extracellular Vesicle Yield and Therapeutic Potential for Bone Defects. ACS NANO 2025; 19:8667-8691. [PMID: 39998493 DOI: 10.1021/acsnano.4c15201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/26/2025]
Abstract
Extracellular vesicles (EVs) hold promise for tissue regeneration, but their low yield and limited therapeutic efficacy hinder clinical translation. Bioreactors provide a larger culture surface area and stable environment for large-scale EV production, yet their ability to enhance EV therapeutic efficacy is limited. Physical stimulation, by inducing cell differentiation and modulating EV cargo composition, offers a more efficient, cost-effective, and reproducible approach compared to the cargo loading of EVs and biochemical priming of parental cells. Herein, the effects of a 3D-printed perfusion bioreactor with a topographical cue on the macrophage EV yield and bioactivity were assessed. The results indicate that the bioreactor increased the EV yield 12.5-fold and enhanced bioactivity in promoting osteogenic differentiation and angiogenesis via upregulated miR-210-3p. Mechanistically, fluid shear stress activates Piezo1, triggering Ca2+ influx and Yes-associated protein (YAP) nuclear translocation, promoting EV secretion and enhancing macrophage M2 polarization in conjunction with morphological changes guided by aligned topography. Moreover, a porous electrospun membrane-hydrogel composite scaffold loaded with bioreactor-derived EVs exhibited outstanding efficacy in promoting osteogenic differentiation and angiogenesis in a rat cranial defect model. This study presents a scalable, cost-effective, and stable platform for the production of therapeutic EVs, potentially overcoming key challenges in translating EV-based therapies to the clinic.
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Affiliation(s)
- Huayi Huang
- Department of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan University, 169 Donghu Street, Wuchang District, Wuhan 430071, Hubei, China
| | - Lingfei Xiao
- Department of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan University, 169 Donghu Street, Wuchang District, Wuhan 430071, Hubei, China
| | - Lucheng Fang
- Department of Otorhinolaryngology, Head and Neck Surgery, Zhongnan Hospital of Wuhan University, 169 Donghu Street, Wuchang District, Wuhan 430071, Hubei, China
| | - Ming Lei
- Department of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan University, 169 Donghu Street, Wuchang District, Wuhan 430071, Hubei, China
| | - Zhibo Liu
- Plastic Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310009 Zhejiang, China
| | - Shijie Gao
- Orthopedic Institute, Department of Orthopaedic Surgery, The First Affiliated Hospital, School of Biology & Basic Medical Sciences, Suzhou Medical College, Soochow University, 899 Pinghai Road, Suzhou 215006, Jiangsu, China
| | - Qingjian Lei
- Department of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan University, 169 Donghu Street, Wuchang District, Wuhan 430071, Hubei, China
| | - Jun Lei
- Department of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan University, 169 Donghu Street, Wuchang District, Wuhan 430071, Hubei, China
| | - Renxiong Wei
- Department of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan University, 169 Donghu Street, Wuchang District, Wuhan 430071, Hubei, China
| | - Yifeng Lei
- The Institute of Technological Science, School of Power and Mechanical Engineering, Wuhan University, 299 Bayi Road, Wuchang District, Wuhan 430072, Hubei, China
| | - Longjian Xue
- The Institute of Technological Science, School of Power and Mechanical Engineering, Wuhan University, 299 Bayi Road, Wuchang District, Wuhan 430072, Hubei, China
| | - Zhen Geng
- Institute of Translational Medicine, Shanghai University, 99 Shangda Road, Baoshan District, Shanghai 200444, China
- National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, 99 Shangda Road, Baoshan District, Shanghai 200444, China
| | - Lin Cai
- Department of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan University, 169 Donghu Street, Wuchang District, Wuhan 430071, Hubei, China
| | - Feifei Yan
- Department of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan University, 169 Donghu Street, Wuchang District, Wuhan 430071, Hubei, China
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Chen X, Ji X, Lao Z, Pan B, Qian Y, Yang W. Role of YAP/TAZ in bone diseases: A transductor from mechanics to biology. J Orthop Translat 2025; 51:13-23. [PMID: 39902099 PMCID: PMC11787699 DOI: 10.1016/j.jot.2024.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 10/24/2024] [Accepted: 12/09/2024] [Indexed: 02/05/2025] Open
Abstract
Wolff's Law and the Mechanostat Theory elucidate how bone tissues detect and convert mechanical stimuli into biological signals, crucial for maintaining bone equilibrium. Abnormal mechanics can lead to diseases such as osteoporosis, osteoarthritis, and nonunion fractures. However, the detailed molecular mechanisms by which mechanical cues are transformed into biological responses in bone remain underexplored. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), key regulators of bone homeostasis, are instrumental in this process. Emerging research highlights bone cells' ability to sense various mechanical stimuli and relay these signals intracellularly. YAP/TAZ are central in receiving these mechanical cues and converting them into signals that influence bone cell behavior. Abnormal YAP/TAZ activity is linked to several bone pathologies, positioning these proteins as promising targets for new treatments. Thus, this review aims to provide an in-depth examination of YAP/TAZ's critical role in the interpretation of mechanical stimuli to biological signals, with a special emphasis on their involvement in bone cell mechanosensing, mechanotransduction, and mechanoresponse. The translational potential of this article: Clinically, appropriate stress stimulation promotes fracture healing, while bed rest can lead to disuse osteoporosis and excessive stress can cause osteoarthritis or bone spurs. Recent advancements in the understanding of YAP/TAZ-mediated mechanobiological signal transduction in bone diseases have been significant, yet many aspects remain unknown. This systematic review summarizes current research progress, identifies unaddressed areas, and highlights potential future research directions. Advancements in this field facilitate a deeper understanding of the molecular mechanisms underlying bone mechanics regulation and underscore the potential of YAP/TAZ as therapeutic targets for bone diseases such as fractures, osteoporosis, and osteoarthritis.
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Affiliation(s)
- Xin Chen
- Department of Orthopedics Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310006, China
| | - Xing Ji
- Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, Department of Clinical Medicine, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, China
| | - Zhaobai Lao
- Department of Orthopedics Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310006, China
| | - Bin Pan
- Department of Orthopedics Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310006, China
| | - Yu Qian
- Department of Orthopedics Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310006, China
| | - Wanlei Yang
- Department of Orthopedics Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310006, China
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Wang Y, Yung P, Lu G, Liu Y, Ding C, Mao C, Li ZA, Tuan RS. Musculoskeletal Organs-on-Chips: An Emerging Platform for Studying the Nanotechnology-Biology Interface. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2025; 37:e2401334. [PMID: 38491868 PMCID: PMC11733728 DOI: 10.1002/adma.202401334] [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: 01/25/2024] [Revised: 03/11/2024] [Indexed: 03/18/2024]
Abstract
Nanotechnology-based approaches are promising for the treatment of musculoskeletal (MSK) disorders, which present significant clinical burdens and challenges, but their clinical translation requires a deep understanding of the complex interplay between nanotechnology and MSK biology. Organ-on-a-chip (OoC) systems have emerged as an innovative and versatile microphysiological platform to replicate the dynamics of tissue microenvironment for studying nanotechnology-biology interactions. This review first covers recent advances and applications of MSK OoCs and their ability to mimic the biophysical and biochemical stimuli encountered by MSK tissues. Next, by integrating nanotechnology into MSK OoCs, cellular responses and tissue behaviors may be investigated by precisely controlling and manipulating the nanoscale environment. Analysis of MSK disease mechanisms, particularly bone, joint, and muscle tissue degeneration, and drug screening and development of personalized medicine may be greatly facilitated using MSK OoCs. Finally, future challenges and directions are outlined for the field, including advanced sensing technologies, integration of immune-active components, and enhancement of biomimetic functionality. By highlighting the emerging applications of MSK OoCs, this review aims to advance the understanding of the intricate nanotechnology-MSK biology interface and its significance in MSK disease management, and the development of innovative and personalized therapeutic and interventional strategies.
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Affiliation(s)
- Yuwen Wang
- Department of Biomedical EngineeringThe Chinese University of Hong KongNTHong Kong SAR999077P. R. China
| | - Patrick Yung
- Center for Neuromusculoskeletal Restorative MedicineHong Kong Science ParkNTHong Kong SAR999077P. R. China
- Department of Orthopaedics and TraumatologyThe Chinese University of Hong KongNTHong Kong SAR999077P. R. China
- Institute for Tissue Engineering and Regenerative MedicineThe Chinese University of Hong KongNTHong Kong SAR999077P. R. China
| | - Gang Lu
- Center for Neuromusculoskeletal Restorative MedicineHong Kong Science ParkNTHong Kong SAR999077P. R. China
- School of Biomedical SciencesThe Chinese University of Hong KongNTHong Kong SAR999077P. R. China
| | - Yuwei Liu
- Department of Biomedical EngineeringThe Chinese University of Hong KongNTHong Kong SAR999077P. R. China
- The First Affiliated Hospital of Shenzhen UniversityShenzhen Second People's HospitalShenzhenGuangdong518037P. R. China
| | - Changhai Ding
- Clinical Research CentreZhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong510260China
- Menzies Institute for Medical ResearchUniversity of TasmaniaHobartTasmania7000Australia
| | - Chuanbin Mao
- Department of Biomedical EngineeringThe Chinese University of Hong KongNTHong Kong SAR999077P. R. China
| | - Zhong Alan Li
- Department of Biomedical EngineeringThe Chinese University of Hong KongNTHong Kong SAR999077P. R. China
- Center for Neuromusculoskeletal Restorative MedicineHong Kong Science ParkNTHong Kong SAR999077P. R. China
- School of Biomedical SciencesThe Chinese University of Hong KongNTHong Kong SAR999077P. R. China
- Key Laboratory of Regenerative MedicineMinistry of EducationSchool of Biomedical SciencesFaculty of MedicineThe Chinese University of Hong KongHong Kong SAR999077P. R. China
- Shenzhen Research InstituteThe Chinese University of Hong KongShenzhen518172P. R. China
| | - Rocky S. Tuan
- Center for Neuromusculoskeletal Restorative MedicineHong Kong Science ParkNTHong Kong SAR999077P. R. China
- Department of Orthopaedics and TraumatologyThe Chinese University of Hong KongNTHong Kong SAR999077P. R. China
- Institute for Tissue Engineering and Regenerative MedicineThe Chinese University of Hong KongNTHong Kong SAR999077P. R. China
- School of Biomedical SciencesThe Chinese University of Hong KongNTHong Kong SAR999077P. R. China
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Giacomini F, Rho HS, Eischen‐Loges M, Tahmasebi Birgani Z, van Blitterswijk C, van Griensven M, Giselbrecht S, Habibović P, Truckenmüller R. Enthesitis on Chip - A Model for Studying Acute and Chronic Inflammation of the Enthesis and its Pharmacological Treatment. Adv Healthc Mater 2024; 13:e2401815. [PMID: 39188199 PMCID: PMC11650547 DOI: 10.1002/adhm.202401815] [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: 06/12/2024] [Revised: 08/14/2024] [Indexed: 08/28/2024]
Abstract
Enthesitis, the inflammation of the enthesis, which is the point of attachment of tendons and ligaments to bones, is a common musculoskeletal disease. The inflammation often originates from the fibrocartilage region of the enthesis as a consequence of mechanical overuse or -load and consequently tissue damage. During enthesitis, waves of inflammatory cytokines propagate in(to) the fibrocartilage, resulting in detrimental, heterotopic bone formation. Understanding of human enthesitis and its treatment options is limited, also because of lacking in vitro model systems that can closely mimic the pathophysiology of the enthesis and can be used to develop therapies. In this study, an enthes(it)is-on-chip model is developed. On opposite sides of a porous culture membrane separating the chip's two microfluidic compartments, human mesenchymal stromal cells are selectively differentiated into tenocytes and fibrochondrocytes. By introducing an inflammatory cytokine cocktail into the fibrochondrocyte compartment, key aspects of acute and chronic enthesitis, measured as increased expression of inflammatory markers, can be recapitulated. Upon inducing chronic inflammatory conditions, hydroxyapatite deposition, enhanced osteogenic marker expression and reduced secretion of tissue-related extracellular matrix components are observed. Adding the anti-inflammatory drug celecoxib to the fibrochondrocyte compartment mitigates the inflammatory state, demonstrating the potential of the enthesitis-on-chip model for drug testing.
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Affiliation(s)
- Francesca Giacomini
- Department of Instructive Biomaterials EngineeringMERLN Institute for Technology‐Inspired Regenerative MedicineMaastricht UniversityUniversiteitssingel 40Maastricht6229 ERThe Netherlands
| | - Hoon Suk Rho
- Department of Instructive Biomaterials EngineeringMERLN Institute for Technology‐Inspired Regenerative MedicineMaastricht UniversityUniversiteitssingel 40Maastricht6229 ERThe Netherlands
| | - Maria Eischen‐Loges
- Department of Instructive Biomaterials EngineeringMERLN Institute for Technology‐Inspired Regenerative MedicineMaastricht UniversityUniversiteitssingel 40Maastricht6229 ERThe Netherlands
- Department of Cell Biology‐Inspired Tissue EngineeringMERLN Institute for Technology‐Inspired Regenerative MedicineMaastricht UniversityUniversiteitssingel 40Maastricht6229 ERThe Netherlands
| | - Zeinab Tahmasebi Birgani
- Department of Instructive Biomaterials EngineeringMERLN Institute for Technology‐Inspired Regenerative MedicineMaastricht UniversityUniversiteitssingel 40Maastricht6229 ERThe Netherlands
| | - Clemens van Blitterswijk
- Department of Instructive Biomaterials EngineeringMERLN Institute for Technology‐Inspired Regenerative MedicineMaastricht UniversityUniversiteitssingel 40Maastricht6229 ERThe Netherlands
- Department of Cell Biology‐Inspired Tissue EngineeringMERLN Institute for Technology‐Inspired Regenerative MedicineMaastricht UniversityUniversiteitssingel 40Maastricht6229 ERThe Netherlands
| | - Martijn van Griensven
- Department of Cell Biology‐Inspired Tissue EngineeringMERLN Institute for Technology‐Inspired Regenerative MedicineMaastricht UniversityUniversiteitssingel 40Maastricht6229 ERThe Netherlands
| | - Stefan Giselbrecht
- Department of Instructive Biomaterials EngineeringMERLN Institute for Technology‐Inspired Regenerative MedicineMaastricht UniversityUniversiteitssingel 40Maastricht6229 ERThe Netherlands
| | - Pamela Habibović
- Department of Instructive Biomaterials EngineeringMERLN Institute for Technology‐Inspired Regenerative MedicineMaastricht UniversityUniversiteitssingel 40Maastricht6229 ERThe Netherlands
| | - Roman Truckenmüller
- Department of Instructive Biomaterials EngineeringMERLN Institute for Technology‐Inspired Regenerative MedicineMaastricht UniversityUniversiteitssingel 40Maastricht6229 ERThe Netherlands
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Lee SH, Li Z, Zhang EY, Kim DH, Huang Z, Lee SJ, Kang HW, Burdick JA, Mauck RL, Heo SC. Precision Repair of Zone-Specific Meniscal Injuries Using a Tunable Extracellular Matrix-Based Hydrogel System. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.09.12.612723. [PMID: 39345590 PMCID: PMC11429709 DOI: 10.1101/2024.09.12.612723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 10/01/2024]
Abstract
Meniscus injuries present significant therapeutic challenges due to their limited self-healing capacity and diverse biological and mechanical properties across meniscal tissue. Conventional repair strategies neglect to replicate the complex zonal characteristics within the meniscus, resulting in suboptimal outcomes. In this study, we introduce an innovative, age- and stiffness-tunable meniscus decellularized extracellular matrix (DEM)-based hydrogel system designed for precision repair of heterogeneous, zonal-dependent meniscus injuries. By synthesizing age-dependent DEM hydrogels, we identified distinct cellular responses: fetal bovine meniscus-derived DEM promoted chondrogenic differentiation, while adult meniscus-derived DEM supported fibrochondrogenic phenotypes. The incorporation of methacrylate hyaluronic acid (MeHA) further refined the mechanical properties and injectability of the DEM-based hydrogels. The combination of age-dependent DEM with MeHA allowed for precise stiffness tuning, influencing cell differentiation and closely mimicking native tissue environments. In vivo tests confirmed the biocompatibility of hydrogels and their integration with native meniscus tissues. Furthermore, advanced 3D bioprinting techniques enabled the fabrication of hybrid hydrogels with biomaterial and mechanical gradients, effectively emulating the zonal properties of meniscus tissue and enhancing cell integration. This study represents a significant advancement in meniscus tissue engineering, providing a promising platform for customized regenerative therapies across a range of heterogeneous fibrous connective tissues.
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Affiliation(s)
- Se-Hwan Lee
- McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States
- Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea
| | - Zizhao Li
- McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States
- Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, United States
| | - Ellen Y. Zhang
- McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States
- Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, United States
| | - Dong Hwa Kim
- McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States
| | - Ziqi Huang
- Biofunctional Materials, Division of Applied Oral Sciences and Community Dental Care, Faculty of Dentistry, The University of Hong Kong, 34 Hospital Road, Sai Ying Pun, Hong Kong SAR, PR China
| | - Sang Jin Lee
- Biofunctional Materials, Division of Applied Oral Sciences and Community Dental Care, Faculty of Dentistry, The University of Hong Kong, 34 Hospital Road, Sai Ying Pun, Hong Kong SAR, PR China
| | - Hyun-Wook Kang
- Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea
| | - Jason A. Burdick
- Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, United States
- BioFrontiers Institute and Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO 80309, United States
| | - Robert L. Mauck
- McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States
- Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, United States
- Translational Musculoskeletal Research Center, Corporal Michael J Crescenz VA Medical Center, Philadelphia, PA 19104, United States
| | - Su Chin Heo
- McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States
- Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, United States
- Translational Musculoskeletal Research Center, Corporal Michael J Crescenz VA Medical Center, Philadelphia, PA 19104, United States
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7
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Wu YC, Yang JY, Hsu CH. Tape-assisted fabrication method for constructing PDMS membrane-containing culture devices with cyclic radial stretching stimulation. ROYAL SOCIETY OPEN SCIENCE 2024; 11:240284. [PMID: 39144495 PMCID: PMC11321861 DOI: 10.1098/rsos.240284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 05/23/2024] [Accepted: 06/27/2024] [Indexed: 08/16/2024]
Abstract
Advanced in vitro culture systems have emerged as alternatives to animal testing and traditional cell culture methods in biomedical research. Polydimethylsiloxane (PDMS) is frequently used in creating sophisticated culture devices owing to its elastomeric properties, which allow mechanical stretching to simulate physiological movements in cell experiments. We introduce a straightforward method that uses three types of commercial tape-generic, magic and masking-to fabricate PDMS membranes with microscale thicknesses (47.2 µm for generic, 58.1 µm for magic and 89.37 µm for masking) in these devices. These membranes are shaped as the bases of culture wells and can perform cyclic radial movements controlled via a vacuum system. In experiments with A549 cells under three mechanical stimulation conditions, we analysed transcriptional regulators responsive to external mechanical stimuli. Results indicated increased nuclear yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) activity in both confluent and densely packed cells under cyclically mechanical strains (Pearson's coefficient (PC) of 0.59 in confluent and 0.24 in dense cells) compared with static (PC = 0.47 in confluent and 0.13 in dense) and stretched conditions (PC = 0.55 in confluent and 0.20 in dense). This technique offers laboratories without microfabrication capabilities a viable option for exploring cellular behaviour under dynamic mechanical stimulation using PDMS membrane-equipped devices.
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Affiliation(s)
- Yun-Chen Wu
- Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli35053, Taiwan
- Institute of Nanoengineering and Microsystems, National Tsing Hua University, Hsinchu30013, Taiwan
| | - Jing-Yi Yang
- Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli35053, Taiwan
| | - Chia-Hsien Hsu
- Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Miaoli35053, Taiwan
- Institute of Nanoengineering and Microsystems, National Tsing Hua University, Hsinchu30013, Taiwan
- Doctoral Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, Taichung40227, Taiwan
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Deng R, Kang R, Jin X, Wang Z, Liu X, Wang Q, Xie L. Mechanical stimulation promotes MSCs healing the lesion of intervertebral disc annulus fibrosus. Front Bioeng Biotechnol 2023; 11:1137199. [PMID: 36845186 PMCID: PMC9950411 DOI: 10.3389/fbioe.2023.1137199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 01/26/2023] [Indexed: 02/12/2023] Open
Abstract
Mesenchymal stem cells (MSCs) and scaffolds offer promising perspectives for annulus fibrosus (AF) repair. The repair effect was linked to features of the local mechanical environment related to the differentiation of MSCs. In this study, we established a Fibrinogen-Thrombin-Genipin (Fib-T-G) gel which is sticky and could transfer strain force from AF tissue to the human mesenchymal stem cells (hMSCs) embedded in the gel. After the Fib-T-G biological gel was injected into the AF fissures, the histology scores of intervertebral disc (IVD) and AF tissue showed that Fib-T-G gel could better repair the AF fissure in caudal IVD of rats, and increase the expression of AF-related proteins including Collagen 1 (COL1), Collagen 2 (COL2) as well as mechanotransduction-related proteins including RhoA and ROCK1. To clarify the mechanism that sticky Fib-T-G gel induces the healing of AF fissures and the differentiation of hMSCs, we further investigated the differentiation of hMSCs under mechanical strain in vitro. It was demonstrated that both AF-specific genes, including Mohawk and SOX-9, and ECM markers (COL1, COL2, aggrecan) of hMSCs were up-regulated in the environment of strain force. Moreover, RhoA/ROCK1 proteins were also found to be significantly up-regulated. In addition, we further -demonstrated that the fibrochondroinductive effect of the mechanical microenvironment process could be significantly blocked or up-regulated by inhibiting the RhoA/ROCK1 pathway or overexpressing RhoA in MSCs, respectively. Summarily, this study will provide a therapeutic alternative to repair AF tears and provide evidence that RhoA/ROCK1 is vital for hMSCs response to mechanical strain and AF-like differentiation.
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Affiliation(s)
- Rongrong Deng
- Third School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Ran Kang
- Third School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China,Department of Orthopedics, Nanjing Lishui Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu, China,*Correspondence: Ran Kang, ; Xin Liu, ; Lin Xie,
| | - Xiaoyu Jin
- Third School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China,Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, Nanjing, Jiangsu, China
| | - Zihan Wang
- Third School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Xin Liu
- Third School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China,*Correspondence: Ran Kang, ; Xin Liu, ; Lin Xie,
| | - Qing Wang
- School of Nursing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Lin Xie
- Third School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China,*Correspondence: Ran Kang, ; Xin Liu, ; Lin Xie,
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9
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Tolabi H, Davari N, Khajehmohammadi M, Malektaj H, Nazemi K, Vahedi S, Ghalandari B, Reis RL, Ghorbani F, Oliveira JM. Progress of Microfluidic Hydrogel-Based Scaffolds and Organ-on-Chips for the Cartilage Tissue Engineering. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2023:e2208852. [PMID: 36633376 DOI: 10.1002/adma.202208852] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 12/09/2022] [Indexed: 05/09/2023]
Abstract
Cartilage degeneration is among the fundamental reasons behind disability and pain across the globe. Numerous approaches have been employed to treat cartilage diseases. Nevertheless, none have shown acceptable outcomes in the long run. In this regard, the convergence of tissue engineering and microfabrication principles can allow developing more advanced microfluidic technologies, thus offering attractive alternatives to current treatments and traditional constructs used in tissue engineering applications. Herein, the current developments involving microfluidic hydrogel-based scaffolds, promising structures for cartilage regeneration, ranging from hydrogels with microfluidic channels to hydrogels prepared by the microfluidic devices, that enable therapeutic delivery of cells, drugs, and growth factors, as well as cartilage-related organ-on-chips are reviewed. Thereafter, cartilage anatomy and types of damages, and present treatment options are briefly overviewed. Various hydrogels are introduced, and the advantages of microfluidic hydrogel-based scaffolds over traditional hydrogels are thoroughly discussed. Furthermore, available technologies for fabricating microfluidic hydrogel-based scaffolds and microfluidic chips are presented. The preclinical and clinical applications of microfluidic hydrogel-based scaffolds in cartilage regeneration and the development of cartilage-related microfluidic chips over time are further explained. The current developments, recent key challenges, and attractive prospects that should be considered so as to develop microfluidic systems in cartilage repair are highlighted.
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Affiliation(s)
- Hamidreza Tolabi
- New Technologies Research Center (NTRC), Amirkabir University of Technology, Tehran, 15875-4413, Iran
- Department of Biomedical Engineering, Amirkabir University of Technology (Tehran Polytechnic), Tehran, 15875-4413, Iran
| | - Niyousha Davari
- Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, 143951561, Iran
| | - Mehran Khajehmohammadi
- Department of Mechanical Engineering, Faculty of Engineering, Yazd University, Yazd, 89195-741, Iran
- Medical Nanotechnology and Tissue Engineering Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, 8916877391, Iran
| | - Haniyeh Malektaj
- Department of Materials and Production, Aalborg University, Fibigerstraede 16, Aalborg, 9220, Denmark
| | - Katayoun Nazemi
- Drug Delivery, Disposition and Dynamics Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, 3052, Australia
| | - Samaneh Vahedi
- Department of Material Science and Engineering, Faculty of Engineering, Imam Khomeini International University, Qazvin, 34149-16818, Iran
| | - Behafarid Ghalandari
- State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China
| | - Rui L Reis
- 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, Barco, Guimarães, 4805-017, Portugal
- ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, 4805-017, Portugal
| | - Farnaz Ghorbani
- Institute of Biomaterials, University of Erlangen-Nuremberg, Cauerstrasse 6, 91058, Erlangen, Germany
| | - Joaquim Miguel Oliveira
- 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, Barco, Guimarães, 4805-017, Portugal
- ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, 4805-017, Portugal
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10
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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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11
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Kobuszewska A, Kolodziejek D, Wojasinski M, Ciach T, Brzozka Z, Jastrzebska E. Study of Stem Cells Influence on Cardiac Cells Cultured with a Cyanide-P-Trifluoromethoxyphenylhydrazone in Organ-on-a-Chip System. BIOSENSORS-BASEL 2021; 11:bios11050131. [PMID: 33922423 PMCID: PMC8145317 DOI: 10.3390/bios11050131] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 04/19/2021] [Accepted: 04/20/2021] [Indexed: 01/09/2023]
Abstract
Regenerative medicine and stem cells could prove to be an effective solution to the problem of treating heart failure caused by ischemic heart disease. However, further studies on the understanding of the processes which occur during the regeneration of damaged tissue are needed. Microfluidic systems, which provide conditions similar to in vivo, could be useful tools for the development of new therapies using stem cells. We investigated how mesenchymal stem cells (MSCs) affect the metabolic activity of cardiac cells (rat cardiomyoblasts and human cardiomyocytes) incubated with a potent uncoupler of mitochondrial oxidative phosphorylation under microfluidic conditions. A cyanide p-trifluoromethoxyphenylhydrazone (FCCP) was used to mimic disfunctions of mitochondria of cardiac cells. The study was performed in a microfluidic system integrated with nanofiber mats made of poly-l-lactid acid (PLLA) or polyurethane (PU). The microsystem geometry allows four different cell cultures to be conducted under different conditions (which we called: normal, abnormal-as both a mono- and co-culture). Metabolic activity of the cells, based on the bioluminescence assay, was assessed in the culture's performed in the microsystem. It was proved that stem cells increased metabolic activity of cardiac cells maintained with FCCP.
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Affiliation(s)
- Anna Kobuszewska
- Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland; (A.K.); (D.K.); (Z.B.)
| | - Dominik Kolodziejek
- Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland; (A.K.); (D.K.); (Z.B.)
| | - Michal Wojasinski
- Department of Biotechnology and Bioprocess Engineering, Faculty of Chemical and Process Engineering, Warsaw University of Technology, Ludwika Waryńskiego 1, 00-645 Warsaw, Poland; (M.W.); (T.C.)
| | - Tomasz Ciach
- Department of Biotechnology and Bioprocess Engineering, Faculty of Chemical and Process Engineering, Warsaw University of Technology, Ludwika Waryńskiego 1, 00-645 Warsaw, Poland; (M.W.); (T.C.)
| | - Zbigniew Brzozka
- Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland; (A.K.); (D.K.); (Z.B.)
| | - Elzbieta Jastrzebska
- Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland; (A.K.); (D.K.); (Z.B.)
- Correspondence:
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12
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Wang S, Hashemi S, Stratton S, Arinzeh TL. The Effect of Physical Cues of Biomaterial Scaffolds on Stem Cell Behavior. Adv Healthc Mater 2021; 10:e2001244. [PMID: 33274860 DOI: 10.1002/adhm.202001244] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 10/09/2020] [Indexed: 02/06/2023]
Abstract
Stem cells have been sought as a promising cell source in the tissue engineering field due to their proliferative capacity as well as differentiation potential. Biomaterials have been utilized to facilitate the delivery of stem cells in order to improve their engraftment and long-term viability upon implantation. Biomaterials also have been developed as scaffolds to promote stem cell induced tissue regeneration. This review focuses on the latter where the biomaterial scaffold is designed to provide physical cues to stem cells in order to promote their behavior for tissue formation. Recent work that explores the effect of scaffold physical properties, topography, mechanical properties and electrical properties, is discussed. Although still being elucidated, the biological mechanisms, including cell shape, focal adhesion distribution, and nuclear shape, are presented. This review also discusses emerging areas and challenges in clinical translation.
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Affiliation(s)
- Shuo Wang
- Department of Biomedical Engineering New Jersey Institute of Technology Newark NJ 07102 USA
| | - Sharareh Hashemi
- Department of Biomedical Engineering New Jersey Institute of Technology Newark NJ 07102 USA
| | - Scott Stratton
- Department of Biomedical Engineering New Jersey Institute of Technology Newark NJ 07102 USA
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13
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Celik C, Franco-Obregón A, Lee EH, Hui JH, Yang Z. Directionalities of magnetic fields and topographic scaffolds synergise to enhance MSC chondrogenesis. Acta Biomater 2021; 119:169-183. [PMID: 33130304 DOI: 10.1016/j.actbio.2020.10.039] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 10/15/2020] [Accepted: 10/26/2020] [Indexed: 12/13/2022]
Abstract
Mesenchymal stem cell (MSC) chondrogenesis is modulated by diverse biophysical cues. We have previously shown that brief, low-amplitude pulsed electromagnetic fields (PEMFs) differentially enhance MSC chondrogenesis in scaffold-free pellet cultures versus conventional tissue culture plastic (TCP), indicating an interplay between magnetism and micromechanical environment. Here, we examined the influence of PEMF directionality over the chondrogenic differentiation of MSCs laden on electrospun fibrous scaffolds of either random (RND) or aligned (ALN) orientations. Correlating MSCs' chondrogenic outcome to pFAK activation and YAP localisation, MSCs on the RND scaffolds experienced the least amount of resting mechanical stress and underwent greatest chondrogenic differentiation in response to brief PEMF exposure (10 min at 1 mT) perpendicular to the dominant plane of the scaffolds (Z-directed). By contrast, in MSC-impregnated RND scaffolds, greatest mitochondrial respiration resulted from X-directed PEMF exposure (parallel to the scaffold plane), and was associated with curtailed chondrogenesis. MSCs on TCP or the ALN scaffolds exhibited greater resting mechanical stress and accordingly, were unresponsive, or negatively responsive, to PEMF exposure from all directions. The efficacy of PEMF-induced MSC chondrogenesis is hence regulated in a multifaceted manner involving focal adhesion dynamics, as well as mitochondrial responses, culminating in a final cellular response. The combined contributions of micromechanical environment and magnetic field orientation hence will need to be considered when designing magnetic exposure paradigms.
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Affiliation(s)
- Cenk Celik
- Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228
| | - Alfredo Franco-Obregón
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228; BioIonic Currents Electromagnetic Pulsing Systems Laboratory, BICEPS, National University of Singapore, Singapore, 117599; Institute for Health Innovation & Technology, iHealthtech, National University of Singapore, Singapore, 117599; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, DSO (Kent Ridge) Building, #04-01, 27 Medical Drive, Singapore, 117593.
| | - Eng Hin Lee
- Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228; Tissue Engineering Program (NUSTEP), Life Sciences Institute, National University of Singapore, DSO (Kent Ridge) Building, #04-01, 27 Medical Drive, Singapore, 117510
| | - James Hp Hui
- Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228; Tissue Engineering Program (NUSTEP), Life Sciences Institute, National University of Singapore, DSO (Kent Ridge) Building, #04-01, 27 Medical Drive, Singapore, 117510
| | - Zheng Yang
- Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228; Tissue Engineering Program (NUSTEP), Life Sciences Institute, National University of Singapore, DSO (Kent Ridge) Building, #04-01, 27 Medical Drive, Singapore, 117510.
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14
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Wang HN, Huang YC, Ni GX. Mechanotransduction of stem cells for tendon repair. World J Stem Cells 2020; 12:952-965. [PMID: 33033557 PMCID: PMC7524696 DOI: 10.4252/wjsc.v12.i9.952] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 05/06/2020] [Accepted: 07/19/2020] [Indexed: 02/06/2023] Open
Abstract
Tendon is a mechanosensitive tissue that transmits force from muscle to bone. Physiological loading contributes to maintaining the homeostasis and adaptation of tendon, but aberrant loading may lead to injury or failed repair. It is shown that stem cells respond to mechanical loading and play an essential role in both acute and chronic injuries, as well as in tendon repair. In the process of mechanotransduction, mechanical loading is detected by mechanosensors that regulate cell differentiation and proliferation via several signaling pathways. In order to better understand the stem-cell response to mechanical stimulation and the potential mechanism of the tendon repair process, in this review, we summarize the source and role of endogenous and exogenous stem cells active in tendon repair, describe the mechanical response of stem cells, and finally, highlight the mechanotransduction process and underlying signaling pathways.
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Affiliation(s)
- Hao-Nan Wang
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Yong-Can Huang
- Shenzhen Engineering Laboratory of Orthopaedic Regenerative Technologies, Department of Spine Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China
| | - Guo-Xin Ni
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China.
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15
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Vashisth P, Kar N, Gupta D, Bellare JR. Three Dimensional Quercetin-Functionalized Patterned Scaffold: Development, Characterization, and In Vitro Assessment for Neural Tissue Engineering. ACS OMEGA 2020; 5:22325-22334. [PMID: 32923790 PMCID: PMC7482233 DOI: 10.1021/acsomega.0c02678] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Accepted: 08/10/2020] [Indexed: 05/06/2023]
Abstract
Regeneration of injured neuronal areas is a big challenge owing to the complex structure and function of the nervous system along with the limited regeneration capacity of neural cells. Recent reports show that patterned and functionalized scaffolds could control neural cell directional growth. In this study, aligned nanofibers (ANFs) were fabricated using a versatile and cost-effective approach, electrospinning, and further processed to make a patterned hybrid scaffold (HANF). The patterned scaffold had circular rings of ANFs reinforced in a biocompatible gellan-gelatin hydrogel matrix to provide adequate mechanical strength and contact guidance for adhesion and growth of neural cells in vitro. Quercetin was loaded into the nanofibrous scaffold to provide a functional agent that supported regeneration of neural cells. The reinforced ANFs enhanced the mechanical strength of the scaffold and provided a cylindrical nerve conduit structure to support neuronal cell growth. The influence of scaffold topology on cell behavior was assessed in in vitro cell culture conditions that revealed that the functionalized patterned scaffolds favored directed neurite cell growth/extension with favored cell culture morphology and showed no cytotoxicity toward neural cells. The results ultimately indicated that the fabricated scaffold has potential for guiding nerve tissue growth and can be used as nerve regeneration scaffolds.
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Affiliation(s)
- Priya Vashisth
- Wadhwani
Research Centre for Bioengineering, Indian
Institute of Technology Bombay, Mumbai, Maharashtra 400076, India
| | - Neelakshi Kar
- Department
of Chemical Engineering, Indian Institute
of Technology Bombay, Mumbai, Maharashtra 400076, India
| | - Deepak Gupta
- Department
of Chemical Engineering, Indian Institute
of Technology Bombay, Mumbai, Maharashtra 400076, India
| | - Jayesh R. Bellare
- Wadhwani
Research Centre for Bioengineering, Indian
Institute of Technology Bombay, Mumbai, Maharashtra 400076, India
- Department
of Chemical Engineering, Indian Institute
of Technology Bombay, Mumbai, Maharashtra 400076, India
- . Phone: +91 22 2576 7207. Fax: +91 22 2572 6895 or +91 22 2572 3480
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16
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Heng BC, Zhang X, Aubel D, Bai Y, Li X, Wei Y, Fussenegger M, Deng X. Role of YAP/TAZ in Cell Lineage Fate Determination and Related Signaling Pathways. Front Cell Dev Biol 2020; 8:735. [PMID: 32850847 PMCID: PMC7406690 DOI: 10.3389/fcell.2020.00735] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 07/15/2020] [Indexed: 12/11/2022] Open
Abstract
The penultimate effectors of the Hippo signaling pathways YAP and TAZ, are transcriptional co-activator proteins that play key roles in many diverse biological processes, ranging from cell proliferation, tumorigenesis, mechanosensing and cell lineage fate determination, to wound healing and regeneration. In this review, we discuss the regulatory mechanisms by which YAP/TAZ control stem/progenitor cell differentiation into the various major lineages that are of interest to tissue engineering and regenerative medicine applications. Of particular interest is the key role of YAP/TAZ in maintaining the delicate balance between quiescence, self-renewal, proliferation and differentiation of endogenous adult stem cells within various tissues/organs during early development, normal homeostasis and regeneration/healing. Finally, we will consider how increasing knowledge of YAP/TAZ signaling might influence the trajectory of future progress in regenerative medicine.
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Affiliation(s)
- Boon C. Heng
- Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China
- Faculty of Science and Technology, Sunway University, Subang Jaya, Malaysia
| | - Xuehui Zhang
- Department of Dental Materials & Dental Medical Devices Testing Center, Peking University School and Hospital of Stomatology, Beijing, China
- National Engineering Laboratory for Digital and Material Technology of Stomatology, NMPA Key Laboratory for Dental Materials, Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Beijing, China
| | - Dominique Aubel
- IUTA Department Genie Biologique, Universite Claude Bernard Lyon 1, Villeurbanne, France
| | - Yunyang Bai
- Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China
| | - Xiaochan Li
- Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China
| | - Yan Wei
- Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China
| | - Martin Fussenegger
- Department of Biosystems Science and Engineering, ETH-Zürich, Basel, Switzerland
| | - Xuliang Deng
- National Engineering Laboratory for Digital and Material Technology of Stomatology, NMPA Key Laboratory for Dental Materials, Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Beijing, China
- Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China
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17
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Tang SW, Tong WY, Pang SW, Voelcker NH, Lam YW. Deconstructing, Replicating, and Engineering Tissue Microenvironment for Stem Cell Differentiation. TISSUE ENGINEERING PART B-REVIEWS 2020; 26:540-554. [PMID: 32242476 DOI: 10.1089/ten.teb.2020.0044] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
One of the most crucial components of regenerative medicine is the controlled differentiation of embryonic or adult stem cells into the desired cell lineage. Although most of the reported protocols of stem cell differentiation involve the use of soluble growth factors, it is increasingly evident that stem cells also undergo differentiation when cultured in the appropriate microenvironment. When cultured in decellularized tissues, for instance, stem cells can recapitulate the morphogenesis and functional specialization of differentiated cell types with speed and efficiency that often surpass the traditional growth factor-driven protocols. This suggests that the tissue microenvironment (TME) provides stem cells with a holistic "instructive niche" that harbors signals for cellular reprogramming. The translation of this into medical applications requires the decoding of these signals, but this has been hampered by the complexity of TME. This problem is often addressed by a reductionist approach, in which cells are exposed to substrates decorated with simple, empirically designed geometries, textures, and chemical compositions ("bottom-up" approach). Although these studies are invaluable in revealing the basic principles of mechanotransduction mechanisms, their physiological relevance is often uncertain. This review examines the recent progress of an alternative, "top-down" approach, in which the TME is treated as a holistic biological entity. This approach is made possible by recent advances in systems biology and fabrication technologies that enable the isolation, characterization, and reconstitution of TME. It is hoped that these new techniques will elucidate the nature of niche signals so that they can be extracted, replicated, and controlled. This review summarizes these emerging techniques and how the data they generated are changing our view on TME. Impact statement This review summarizes the current state of art of the understanding of instructive niche in the field of tissue microenvironment. Not only did we survey the use of different biochemical preparations as stimuli of stem cell differentiation and summarize the recent effort in dissecting the biochemical composition of these preparations, through the application of extracellular matrix (ECM) arrays and proteomics, but we also introduce the use of open-source, high-content immunohistochemistry projects in contributing to the understanding of tissue-specific composition of ECM. We believe this review would be highly useful for our peer researching in the same field. "Mr. Tulkinghorn is always the same… so oddly out of place and yet so perfectly at home." -Charles Dickens, Bleak House.
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Affiliation(s)
- Sze Wing Tang
- Department of Chemistry, City University of Hong Kong, Hong Kong, Hong Kong
| | - Wing Yin Tong
- Melbourne Center for Nanofabrication, Victorian Node of the Australian National Fabrication, Clayton, Australia.,Drug Delivery Disposition & Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia
| | - Stella W Pang
- Department of Electrical Engineering, City University of Hong Kong, Hong Kong, Hong Kong
| | - Nicolas H Voelcker
- Melbourne Center for Nanofabrication, Victorian Node of the Australian National Fabrication, Clayton, Australia.,Drug Delivery Disposition & Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia
| | - Yun Wah Lam
- Department of Chemistry, City University of Hong Kong, Hong Kong, Hong Kong
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18
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Gegg C, Yang F. The Effects of ROCK Inhibition on Mesenchymal Stem Cell Chondrogenesis Are Culture Model Dependent. Tissue Eng Part A 2019; 26:130-139. [PMID: 31411113 DOI: 10.1089/ten.tea.2019.0068] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Rho-associated protein kinase (ROCK) signaling correlates with cell shape, with decreased cell spreading accompanied by decreased ROCK activity. However, how cell shape and ROCK activity impact the chondrogenesis of mesenchymal stem cells (MSCs) remains inconclusive. Here we examine the effects of ROCK inhibition on human MSC chondrogenesis in four different culture models, including three-dimensional (3D) microribbon (μRB) scaffolds, two-dimensional hydrogel (2D-HG) substrates, 3D hydrogels (3D-HGs), and pellet. For each culture model involving biomaterials, four polymers were compared, including gelatin, chondroitin sulfate, hyaluronic acid, and polyethylene glycol. ROCK inhibition decreased MSC chondrogenesis in μRB model, enhanced chondrogenesis in pellet, and had minimal effect in 2D-HG or 3D-HG models. Furthermore, we demonstrate that MSC chondrogenesis cannot be predicted using ROCK signaling alone. While varying biomaterial compositions can impact the amount or phenotype of resulting cartilage, varying biomaterials did not change the chondrogenic response to ROCK inhibition within each culture model. Regardless of culture model or ROCK expression, increased cartilage formation was always accompanied by enhanced N-cadherin expression and production, suggesting that N-cadherin is a robust marker to select culture conditions that promote chondrogenesis. Together, the results from this study may be used to enhance MSC-based cartilage regeneration in different culture models. Impact Statement Here we assessed the effects of Rho-associated protein kinase (ROCK) inhibition on mesenchymal stem cell (MSC) chondrogenesis in different culture models, including three-dimensional (3D) microribbon scaffolds, two-dimensional hydrogel substrates, 3D hydrogels, and pellet culture. Our results demonstrate that effects of ROCK inhibition on MSC chondrogenesis differ substantially depending on culture models. Furthermore, MSC chondrogenesis cannot be predicted using ROCK signaling alone. The results from this study fill in a gap of knowledge in the correlation between ROCK signaling and MSC chondrogenesis, which may be used to enhance MSC-based cartilage regeneration in different culture models.
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Affiliation(s)
- Courtney Gegg
- Department of Bioengineering, Stanford University Schools of Engineering and Medicine, Stanford, California
| | - Fan Yang
- Department of Bioengineering and Orthopedic Surgery, Stanford University Schools of Engineering and Medicine, Stanford, California
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Gonzalez-Fernandez T, Sikorski P, Leach JK. Bio-instructive materials for musculoskeletal regeneration. Acta Biomater 2019; 96:20-34. [PMID: 31302298 PMCID: PMC6717669 DOI: 10.1016/j.actbio.2019.07.014] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Revised: 06/26/2019] [Accepted: 07/09/2019] [Indexed: 02/06/2023]
Abstract
The prevalence and cost of disorders affecting the musculoskeletal system are predicted to rise significantly in the coming years due to the aging global population and the increase of associated risk factors. Despite being the second largest cause of disability, the clinical options for therapeutic intervention remain limited. The clinical translation of cell-based therapies for the treatment of musculoskeletal disorders faces many challenges including maintenance of cell survival in the harsh in vivo environment and the lack of control over regulating cell phenotype upon implantation. In order to address these challenges, the development of bio-instructive materials to modulate cell behavior has taken center stage as a strategy to increase the therapeutic potential of various cell populations. However, the determination of the necessary cues for a specific application and how these signals should be presented from a biomaterial remains elusive. This review highlights recent biochemical and physical strategies used to engineer bio-instructive materials for the repair of musculoskeletal tissues. There is a particular emphasis on emerging efforts such as the engineering of immunomodulatory and antibacterial materials, as well as the incorporation of these strategies into biofabrication and organ-on-a-chip approaches. STATEMENT OF SIGNIFICANCE: Disorders affecting the musculoskeletal system affect individuals across the lifespan and have a profound effect on mobility and quality of life. While small defects in many tissues can heal successfully, larger defects are often unable to heal or instead heal with inferior quality fibrous tissue and require clinical intervention. Cell-based therapies are a promising option for clinical translation, yet challenges related to maintaining cell survival and instructing cell phenotype upon implantation have limited the success of this approach. Bio-instructive materials provide an exciting opportunity to modulate cell behavior and enhance the efficacy of cell-based approaches for musculoskeletal repair. However, the identification of critical instructive cues and how to present these stimuli is a focus of intense investigation. This review highlights recent biochemical and physical strategies used to engineer bio-instructive materials for the repair of musculoskeletal tissues, while also considering exciting progress in the engineering of immunomodulatory and antibacterial materials.
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Affiliation(s)
| | - Pawel Sikorski
- Department of Biomedical Engineering, University of California, Davis, Davis, CA, USA; Department of Physics, Norwegian University of Science and Technology, NTNU, Trondheim, Norway
| | - J Kent Leach
- Department of Biomedical Engineering, University of California, Davis, Davis, CA, USA; Department of Orthopaedic Surgery, School of Medicine, UC Davis Health, Sacramento, CA, USA.
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20
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Lolli A, Colella F, De Bari C, van Osch GJVM. Targeting anti-chondrogenic factors for the stimulation of chondrogenesis: A new paradigm in cartilage repair. J Orthop Res 2019; 37:12-22. [PMID: 30175861 DOI: 10.1002/jor.24136] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2018] [Accepted: 08/09/2018] [Indexed: 02/04/2023]
Abstract
Trauma and age-related cartilage disorders represent a major global cause of morbidity, resulting in chronic pain and disability in patients. A lack of effective therapies, together with a rapidly aging population, creates an impressive clinical and economic burden on healthcare systems. In this scenario, experimental therapies based on transplantation or in situ stimulation of skeletal Mesenchymal Stem/progenitor Cells (MSCs) have raised great interest for cartilage repair. Nevertheless, the challenge of guiding MSC differentiation and preventing cartilage hypertrophy and calcification still needs to be overcome. While research has mostly focused on the stimulation of cartilage anabolism using growth factors, several issues remain unresolved prompting the field to search for novel solutions. Recently, inhibition of anti-chondrogenic regulators has emerged as an intriguing opportunity. Anti-chondrogenic regulators include extracellular proteins as well as intracellular transcription factors and microRNAs that act as potent inhibitors of pro-chondrogenic signals. Suppression of these inhibitors can enhance MSC chondrogenesis and production of cartilage matrix. We here review the current knowledge concerning different types of anti-chondrogenic regulators. We aim to highlight novel therapeutic targets for cartilage repair and discuss suitable tools for suppressing their anti-chondrogenic functions. Further effort is needed to unveil the therapeutic perspectives of this approach and pave the way for effective treatment of cartilage injuries in patients. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
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Affiliation(s)
- Andrea Lolli
- Department of Orthopaedics, Erasmus MC, University Medical Center, Wytemaweg 80, 3015CN Rotterdam, the Netherlands
| | - Fabio Colella
- Arthritis and Regenerative Medicine Laboratory, Aberdeen Centre for Arthritis and Musculoskeletal Health, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom
| | - Cosimo De Bari
- Arthritis and Regenerative Medicine Laboratory, Aberdeen Centre for Arthritis and Musculoskeletal Health, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom
| | - Gerjo J V M van Osch
- Department of Orthopaedics, Erasmus MC, University Medical Center, Wytemaweg 80, 3015CN Rotterdam, the Netherlands.,Department of Otorhinolaryngology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands
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21
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Brusatin G, Panciera T, Gandin A, Citron A, Piccolo S. Biomaterials and engineered microenvironments to control YAP/TAZ-dependent cell behaviour. NATURE MATERIALS 2018; 17:1063-1075. [PMID: 30374202 PMCID: PMC6992423 DOI: 10.1038/s41563-018-0180-8] [Citation(s) in RCA: 167] [Impact Index Per Article: 23.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Accepted: 08/29/2018] [Indexed: 05/11/2023]
Abstract
Mechanical signals are increasingly recognized as overarching regulators of cell behaviour, controlling stemness, organoid biology, tissue development and regeneration. Moreover, aberrant mechanotransduction is a driver of disease, including cancer, fibrosis and cardiovascular defects. A central question remains how cells compute a host of biomechanical signals into meaningful biological behaviours. Biomaterials and microfabrication technologies are essential to address this issue. Here we review a large body of evidence that connects diverse biomaterial-based systems to the functions of YAP/TAZ, two highly related mechanosensitive transcriptional regulators. YAP/TAZ orchestrate the response to a suite of engineered microenviroments, emerging as a universal control system for cells in two and three dimensions, in static or dynamic fashions, over a range of elastic and viscoelastic stimuli, from solid to fluid states. This approach may guide the rational design of technological and material-based platforms with dramatically improved functionalities and inform the generation of new biomaterials for regenerative medicine applications.
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Affiliation(s)
- Giovanna Brusatin
- Department of Industrial Engineering (DII) and INSTM, University of Padua, Padua, Italy
| | - Tito Panciera
- Department of Molecular Medicine (DMM), University of Padua School of Medicine, Padua, Italy
| | - Alessandro Gandin
- Department of Industrial Engineering (DII) and INSTM, University of Padua, Padua, Italy
- Department of Molecular Medicine (DMM), University of Padua School of Medicine, Padua, Italy
| | - Anna Citron
- Department of Molecular Medicine (DMM), University of Padua School of Medicine, Padua, Italy
| | - Stefano Piccolo
- Department of Molecular Medicine (DMM), University of Padua School of Medicine, Padua, Italy.
- IFOM-the FIRC Institute of Molecular Oncology, .
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22
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Lopes D, Martins-Cruz C, Oliveira MB, Mano JF. Bone physiology as inspiration for tissue regenerative therapies. Biomaterials 2018; 185:240-275. [PMID: 30261426 PMCID: PMC6445367 DOI: 10.1016/j.biomaterials.2018.09.028] [Citation(s) in RCA: 236] [Impact Index Per Article: 33.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Revised: 09/15/2018] [Accepted: 09/17/2018] [Indexed: 12/14/2022]
Abstract
The development, maintenance of healthy bone and regeneration of injured tissue in the human body comprise a set of intricate and finely coordinated processes. However, an analysis of current bone regeneration strategies shows that only a small fraction of well-reported bone biology aspects has been used as inspiration and transposed into the development of therapeutic products. Specific topics that include inter-scale bone structural organization, developmental aspects of bone morphogenesis, bone repair mechanisms, role of specific cells and heterotypic cell contact in the bone niche (including vascularization networks and immune system cells), cell-cell direct and soluble-mediated contact, extracellular matrix composition (with particular focus on the non-soluble fraction of proteins), as well as mechanical aspects of native bone will be the main reviewed topics. In this Review we suggest a systematic parallelization of (i) fundamental well-established biology of bone, (ii) updated and recent advances on the understanding of biological phenomena occurring in native and injured tissue, and (iii) critical discussion of how those individual aspects have been translated into tissue regeneration strategies using biomaterials and other tissue engineering approaches. We aim at presenting a perspective on unexplored aspects of bone physiology and how they could be translated into innovative regeneration-driven concepts.
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Affiliation(s)
- Diana Lopes
- Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro, Campus Universitário de Santiago,, 3810 193 Aveiro, Portugal
| | - Cláudia Martins-Cruz
- Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro, Campus Universitário de Santiago,, 3810 193 Aveiro, Portugal
| | - Mariana B Oliveira
- Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro, Campus Universitário de Santiago,, 3810 193 Aveiro, Portugal.
| | - João F Mano
- Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro, Campus Universitário de Santiago,, 3810 193 Aveiro, Portugal.
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23
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方 未, 顾 婷, 刘 毅, 徐 兰, 陈 跃. [The application of nanotopography in the development of tissue engineered tissues using mesenchymal stem cells]. SHENG WU YI XUE GONG CHENG XUE ZA ZHI = JOURNAL OF BIOMEDICAL ENGINEERING = SHENGWU YIXUE GONGCHENGXUE ZAZHI 2018; 35:145-150. [PMID: 29745614 PMCID: PMC10307557 DOI: 10.7507/1001-5515.201705077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 05/26/2017] [Indexed: 11/03/2022]
Abstract
Tissue engineering has emerged as a promising approach for the repair and functional reconstruction of damaged tissues. The bionic and intelligentized scaffolds provide the structural support for cell growth and differentiation as well as tissue regeneration. The surface properties of the biological material implant, the nanotopology in particular, become key aspects in determining the success of the implant. Mesenchymal stem cells (MSC) are widely favored by researchers as the seed cells in tissue engineering. Recently, it has been shown that nanotopographical characteristics of biomaterials regulate a wide range of MSC properties from their cellular behavior and differentiation potential. Herein, this review will provide an update on studies investigating the roles of nanotopography in the development of tissue engineering using MSC.
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Affiliation(s)
- 未英 方
- 中国科学院上海生命科学研究院/中国科学院典型培养物保藏委员会 细胞库/干细胞库（上海 200031）Cell Bank/Stem Cell Bank, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R.China
- 上海交通大学 生命科学技术学院（上海 200240）School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, P.R.China
| | - 婷玉 顾
- 中国科学院上海生命科学研究院/中国科学院典型培养物保藏委员会 细胞库/干细胞库（上海 200031）Cell Bank/Stem Cell Bank, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R.China
| | - 毅 刘
- 中国科学院上海生命科学研究院/中国科学院典型培养物保藏委员会 细胞库/干细胞库（上海 200031）Cell Bank/Stem Cell Bank, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R.China
| | - 兰 徐
- 中国科学院上海生命科学研究院/中国科学院典型培养物保藏委员会 细胞库/干细胞库（上海 200031）Cell Bank/Stem Cell Bank, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R.China
| | - 跃磊 陈
- 中国科学院上海生命科学研究院/中国科学院典型培养物保藏委员会 细胞库/干细胞库（上海 200031）Cell Bank/Stem Cell Bank, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R.China
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24
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Lopa S, Mondadori C, Mainardi VL, Talò G, Costantini M, Candrian C, Święszkowski W, Moretti M. Translational Application of Microfluidics and Bioprinting for Stem Cell-Based Cartilage Repair. Stem Cells Int 2018; 2018:6594841. [PMID: 29535776 PMCID: PMC5838503 DOI: 10.1155/2018/6594841] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Revised: 11/06/2017] [Accepted: 12/05/2017] [Indexed: 01/09/2023] Open
Abstract
Cartilage defects can impair the most elementary daily activities and, if not properly treated, can lead to the complete loss of articular function. The limitations of standard treatments for cartilage repair have triggered the development of stem cell-based therapies. In this scenario, the development of efficient cell differentiation protocols and the design of proper biomaterial-based supports to deliver cells to the injury site need to be addressed through basic and applied research to fully exploit the potential of stem cells. Here, we discuss the use of microfluidics and bioprinting approaches for the translation of stem cell-based therapy for cartilage repair in clinics. In particular, we will focus on the optimization of hydrogel-based materials to mimic the articular cartilage triggered by their use as bioinks in 3D bioprinting applications, on the screening of biochemical and biophysical factors through microfluidic devices to enhance stem cell chondrogenesis, and on the use of microfluidic technology to generate implantable constructs with a complex geometry. Finally, we will describe some new bioprinting applications that pave the way to the clinical use of stem cell-based therapies, such as scaffold-free bioprinting and the development of a 3D handheld device for the in situ repair of cartilage defects.
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Affiliation(s)
- Silvia Lopa
- Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, Milan, Italy
| | - Carlotta Mondadori
- Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, Milan, Italy
- Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy
| | - Valerio Luca Mainardi
- Regenerative Medicine Technologies Lab, Ente Ospedaliero Cantonale (EOC), Lugano, Switzerland
- Laboratory of Biological Structures Mechanics-Chemistry, Material and Chemical Engineering Department “Giulio Natta”, Politecnico di Milano, Milan, Italy
| | - Giuseppe Talò
- Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, Milan, Italy
| | - Marco Costantini
- Department of Chemistry, Sapienza University of Rome, Rome, Italy
| | - Christian Candrian
- Regenerative Medicine Technologies Lab, Ente Ospedaliero Cantonale (EOC), Lugano, Switzerland
- Unità di Traumatologia e Ortopedia-ORL, Ente Ospedaliero Cantonale (EOC), Lugano, Switzerland
| | - Wojciech Święszkowski
- Faculty of Materials Science and Engineering, Warsaw University of Technology, Warsaw, Poland
| | - Matteo Moretti
- Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, Milan, Italy
- Regenerative Medicine Technologies Lab, Ente Ospedaliero Cantonale (EOC), Lugano, Switzerland
- Swiss Institute for Regenerative Medicine, Lugano, Switzerland
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25
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Panciera T, Azzolin L, Cordenonsi M, Piccolo S. Mechanobiology of YAP and TAZ in physiology and disease. Nat Rev Mol Cell Biol 2017; 18:758-770. [PMID: 28951564 PMCID: PMC6192510 DOI: 10.1038/nrm.2017.87] [Citation(s) in RCA: 919] [Impact Index Per Article: 114.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
A growing body of evidence suggests that mechanical signals emanating from the cell's microenvironment are fundamental regulators of cell behaviour. Moreover, at the macroscopic scale, the influence of forces, such as the forces generated by blood flow, muscle contraction, gravity and overall tissue rigidity (for example, inside of a tumour lump), is central to our understanding of physiology and disease pathogenesis. Still, how mechanical cues are sensed and transduced at the molecular level to regulate gene expression has long remained enigmatic. The identification of the transcription factors YAP and TAZ as mechanotransducers started to fill this gap. YAP and TAZ read a broad range of mechanical cues, from shear stress to cell shape and extracellular matrix rigidity, and translate them into cell-specific transcriptional programmes. YAP and TAZ mechanotransduction is critical for driving stem cell behaviour and regeneration, and it sheds new light on the mechanisms by which aberrant cell mechanics is instrumental for the onset of multiple diseases, such as atherosclerosis, fibrosis, pulmonary hypertension, inflammation, muscular dystrophy and cancer.
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Affiliation(s)
- Tito Panciera
- Department of Molecular Medicine, University of Padua School of Medicine, viale Colombo 3, 35126 Padua, Italy
| | - Luca Azzolin
- Department of Molecular Medicine, University of Padua School of Medicine, viale Colombo 3, 35126 Padua, Italy
| | - Michelangelo Cordenonsi
- Department of Molecular Medicine, University of Padua School of Medicine, viale Colombo 3, 35126 Padua, Italy
| | - Stefano Piccolo
- Department of Molecular Medicine, University of Padua School of Medicine, viale Colombo 3, 35126 Padua, Italy
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26
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Chiu DT, deMello AJ, Di Carlo D, Doyle PS, Hansen C, Maceiczyk RM, Wootton RC. Small but Perfectly Formed? Successes, Challenges, and Opportunities for Microfluidics in the Chemical and Biological Sciences. Chem 2017. [DOI: 10.1016/j.chempr.2017.01.009] [Citation(s) in RCA: 212] [Impact Index Per Article: 26.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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27
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Hadden WJ, Choi YS. The extracellular microscape governs mesenchymal stem cell fate. J Biol Eng 2016; 10:16. [PMID: 27895704 PMCID: PMC5117578 DOI: 10.1186/s13036-016-0037-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Accepted: 11/09/2016] [Indexed: 12/15/2022] Open
Abstract
Each cell forever interacts with its extracellular matrix (ECM); a stem cell relies on this interaction to guide differentiation. The stiffness, nanotopography, protein composition, stress and strain inherent to any given ECM influences stem cell lineage commitment. This interaction is dynamic, multidimensional and reciprocally evolving through time, and from this concerted exchange the macroscopic tissues that comprise living organisms are formed. Mesenchymal stem cells can give rise to bone, cartilage, tendon and muscle; thus attempts to manipulate their differentiation must heed the physical properties of incredibly complex native microenvironments to realize regenerative goals.
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Affiliation(s)
- William J Hadden
- University of Sydney Medical School & Kolling Institute of Medical Research, Sydney, NSW Australia
| | - Yu Suk Choi
- School of Anatomy, Physiology and Human Biology, University of Western Australia, Entrance 2, Hackett Dr, M309, Level 1, Crawley, WA 6009 Australia
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28
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Wu Q, Chen B, Liang Z. Mesenchymal Stem Cells as a Prospective Therapy for the Diabetic Foot. Stem Cells Int 2016; 2016:4612167. [PMID: 27867398 PMCID: PMC5102750 DOI: 10.1155/2016/4612167] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2016] [Revised: 09/28/2016] [Accepted: 10/10/2016] [Indexed: 12/14/2022] Open
Abstract
The diabetic foot is a serious complication of diabetes. Mesenchymal stem cells are an abundant source of stem cells which occupy a special position in cell therapies, and recent studies have suggested that mesenchymal stem cells can play essential roles in treatments for the diabetic foot. Here, we discuss the advances that have been made in mesenchymal stem cell treatments for this condition. The roles and functional mechanisms of mesenchymal stem cells in the diabetic foot are also summarized, and insights into current and future studies are presented.
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Affiliation(s)
- Qinan Wu
- Department of Endocrinology, The First Affiliated Hospital of The Third Military Medical University, Chongqing 400038, China
| | - Bing Chen
- Department of Endocrinology, The First Affiliated Hospital of The Third Military Medical University, Chongqing 400038, China
| | - Ziwen Liang
- Department of Endocrinology, The First Affiliated Hospital of The Third Military Medical University, Chongqing 400038, China
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29
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Andalib MN, Dzenis Y, Donahue HJ, Lim JY. Biomimetic substrate control of cellular mechanotransduction. Biomater Res 2016; 20:11. [PMID: 27134756 PMCID: PMC4850706 DOI: 10.1186/s40824-016-0059-1] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2016] [Accepted: 04/12/2016] [Indexed: 02/06/2023] Open
Abstract
Extracellular mechanophysical signals from both static substrate cue and dynamic mechanical loading have strong potential to regulate cell functions. Most of the studies have adopted either static or dynamic cue and shown that each cue can regulate cell adhesion, spreading, migration, proliferation, lineage commitment, and differentiation. However, there is limited information on the integrative control of cell functions by the static and dynamic mechanophysical signals. For example, a majority of dynamic loading studies have tested mechanical stimulation of cells utilizing cultures on flat surfaces without any surface modification. While these approaches have provided significant information on cell mechanotransduction, obtained outcomes may not correctly recapitulate complex cellular mechanosensing milieus in vivo. Several pioneering studies documented cellular response to mechanical stimulations upon cultures with biomimetic substrate modifications. In this min-review, we will highlight key findings on the integrative role of substrate cue (topographic, geometric, etc.) and mechanical stimulation (stretch, fluid shear) in modulating cell function and fate. The integrative approaches, though not fully established yet, will help properly understand cell mechanotransduction under biomimetic mechanophysical environments. This may further lead to advanced functional tissue engineering and regenerative medicine protocols.
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Affiliation(s)
- Mohammad Nahid Andalib
- Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, W317.3 Nebraska Hall, Lincoln, NE 68588-0526 USA
| | - Yuris Dzenis
- Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, W317.3 Nebraska Hall, Lincoln, NE 68588-0526 USA
| | - Henry J Donahue
- Department of Biomedical Engineering, Virginia Commonwealth University, 401 West Main Street, P.O. Box 843067, Richmond, VA 23284-3067 USA
| | - Jung Yul Lim
- Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, W317.3 Nebraska Hall, Lincoln, NE 68588-0526 USA
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Park D, Lim J, Park JY, Lee SH. Concise Review: Stem Cell Microenvironment on a Chip: Current Technologies for Tissue Engineering and Stem Cell Biology. Stem Cells Transl Med 2015; 4:1352-68. [PMID: 26450425 DOI: 10.5966/sctm.2015-0095] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2015] [Accepted: 07/29/2015] [Indexed: 01/09/2023] Open
Abstract
UNLABELLED Stem cells have huge potential in many therapeutic areas. With conventional cell culture methods, however, it is difficult to achieve in vivo-like microenvironments in which a number of well-controlled stimuli are provided for growing highly sensitive stem cells. In contrast, microtechnology-based platforms offer advantages of high precision, controllability, scalability, and reproducibility, enabling imitation of the complex physiological context of in vivo. This capability may fill the gap between the present knowledge about stem cells and that required for clinical stem cell-based therapies. We reviewed the various types of microplatforms on which stem cell microenvironments are mimicked. We have assigned the various microplatforms to four categories based on their practical uses to assist stem cell biologists in using them for research. In particular, many examples are given of microplatforms used for the production of embryoid bodies and aggregates of stem cells in vitro. We also categorized microplatforms based on the types of factors controlling the behaviors of stem cells. Finally, we outline possible future directions for microplatform-based stem cell research, such as research leading to the production of well-defined environments for stem cells to be used in scaled-up systems or organs-on-a-chip, the regulation of induced pluripotent stem cells, and the study of the genetic states of stem cells on microplatforms. SIGNIFICANCE Stem cells are highly sensitive to a variety of physicochemical cues, and their fate can be easily altered by a slight change of environment; therefore, systematic analysis and discrimination of the extracellular signals and intracellular pathways controlling the fate of cells and experimental realization of sensitive and controllable niche environments are critical. This review introduces diverse microplatforms to provide in vitro stem cell niches. Microplatforms could control microenvironments around cells and have recently attracted much attention in biology including stem cell research. These microplatforms and the future directions of stem cell microenvironment are described.
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Affiliation(s)
- DoYeun Park
- KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Republic of Korea
| | - Jaeho Lim
- School of Biomedical Engineering, College of Health Science, Korea University, Seoul, Republic of Korea
| | - Joong Yull Park
- School of Mechanical Engineering, College of Engineering, Chung-ang University, Seoul, Republic of Korea
| | - Sang-Hoon Lee
- KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Republic of Korea School of Biomedical Engineering, College of Health Science, Korea University, Seoul, Republic of Korea
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Karystinou A, Roelofs AJ, Neve A, Cantatore FP, Wackerhage H, De Bari C. Yes-associated protein (YAP) is a negative regulator of chondrogenesis in mesenchymal stem cells. Arthritis Res Ther 2015; 17:147. [PMID: 26025096 PMCID: PMC4449558 DOI: 10.1186/s13075-015-0639-9] [Citation(s) in RCA: 101] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2014] [Accepted: 04/24/2015] [Indexed: 11/10/2022] Open
Abstract
Introduction The control of differentiation of mesenchymal stromal/stem cells (MSCs) is crucial for tissue engineering strategies employing MSCs. The purpose of this study was to investigate whether the transcriptional co-factor Yes-associated protein (YAP) regulates chondrogenic differentiation of MSCs. Methods Expression of total YAP, its paralogue transcriptional co-activator with PDZ-binding motif (TAZ), and individual YAP transcript variants during in vitro chondrogenesis of human MSCs was determined by quantitative reverse transcription polymerase chain reaction (RT-PCR). YAP expression was confirmed by western blotting. To determine the effect of high YAP activity on chondrogenesis, C3H10T1/2 MSC-like cells were transduced with human (h)YAP and treated in micromass with bone morphogenetic protein-2 (BMP-2). Chondrogenic differentiation was assessed by alcian blue staining and expression of chondrocyte-lineage genes. BMP signalling was determined by detection of pSmad1,5,8 by western blotting and expression of BMP target genes by quantitative RT-PCR. Finally, YAP and pYAP were detected in mouse embryo hindlimbs by immunohistochemistry. Results YAP, but not TAZ, was downregulated during in vitro chondrogenesis of human MSCs. One of the YAP transcript variants, however, was upregulated in high-density micromass culture. Overexpression of hYAP in murine C3H10T1/2 MSCs inhibited chondrogenic differentiation. High YAP activity in these cells decreased Smad1,5,8 phosphorylation and expression of the BMP target genes Inhibitor of DNA binding/differentiation (Id)1, Id2 and Id3 in response to BMP-2. In developing mouse limbs, Yap was nuclear in the perichondrium while mostly phosphorylated and cytosolic in cells of the cartilage anlage, suggesting downregulation of Yap co-transcriptional activity during physiological chondrogenesis in vivo. Conclusions Our findings indicate that YAP is a negative regulator of chondrogenic differentiation of MSCs. Downregulation of YAP is required for chondrogenesis through derepression of chondrogenic signalling. Therapeutic targeting of YAP to promote cartilage repair and prevent secondary osteoarthritis is an exciting prospect in rheumatology. Electronic supplementary material The online version of this article (doi:10.1186/s13075-015-0639-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Alexandra Karystinou
- Musculoskeletal Research Programme, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.
| | - Anke J Roelofs
- Musculoskeletal Research Programme, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.
| | - Anna Neve
- Musculoskeletal Research Programme, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK. .,Rheumatology Clinic, Department of Medical and Surgical Sciences, University of Foggia, Via Napoli 25, 71122, Foggia, Italy.
| | - Francesco P Cantatore
- Rheumatology Clinic, Department of Medical and Surgical Sciences, University of Foggia, Via Napoli 25, 71122, Foggia, Italy.
| | - Henning Wackerhage
- Musculoskeletal Research Programme, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.
| | - Cosimo De Bari
- Musculoskeletal Research Programme, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.
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Salmasi S, Kalaskar DM, Yoon WW, Blunn GW, Seifalian AM. Role of nanotopography in the development of tissue engineered 3D organs and tissues using mesenchymal stem cells. World J Stem Cells 2015; 7:266-80. [PMID: 25815114 PMCID: PMC4369486 DOI: 10.4252/wjsc.v7.i2.266] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2014] [Revised: 11/07/2014] [Accepted: 12/03/2014] [Indexed: 02/06/2023] Open
Abstract
Recent regenerative medicine and tissue engineering strategies (using cells, scaffolds, medical devices and gene therapy) have led to fascinating progress of translation of basic research towards clinical applications. In the past decade, great deal of research has focused on developing various three dimensional (3D) organs, such as bone, skin, liver, kidney and ear, using such strategies in order to replace or regenerate damaged organs for the purpose of maintaining or restoring organs' functions that may have been lost due to aging, accident or disease. The surface properties of a material or a device are key aspects in determining the success of the implant in biomedicine, as the majority of biological reactions in human body occur on surfaces or interfaces. Furthermore, it has been established in the literature that cell adhesion and proliferation are, to a great extent, influenced by the micro- and nano-surface characteristics of biomaterials and devices. In addition, it has been shown that the functions of stem cells, mesenchymal stem cells in particular, could be regulated through physical interaction with specific nanotopographical cues. Therefore, guided stem cell proliferation, differentiation and function are of great importance in the regeneration of 3D tissues and organs using tissue engineering strategies. This review will provide an update on the impact of nanotopography on mesenchymal stem cells for the purpose of developing laboratory-based 3D organs and tissues, as well as the most recent research and case studies on this topic.
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Affiliation(s)
- Shima Salmasi
- Shima Salmasi, Deepak M Kalaskar, Alexander M Seifalian, UCL Division of Surgery and Interventional Science, Centre for Nanotechnology and Regenerative Medicine, University College London, NW3 2PF London, United Kingdom
| | - Deepak M Kalaskar
- Shima Salmasi, Deepak M Kalaskar, Alexander M Seifalian, UCL Division of Surgery and Interventional Science, Centre for Nanotechnology and Regenerative Medicine, University College London, NW3 2PF London, United Kingdom
| | - Wai-Weng Yoon
- Shima Salmasi, Deepak M Kalaskar, Alexander M Seifalian, UCL Division of Surgery and Interventional Science, Centre for Nanotechnology and Regenerative Medicine, University College London, NW3 2PF London, United Kingdom
| | - Gordon W Blunn
- Shima Salmasi, Deepak M Kalaskar, Alexander M Seifalian, UCL Division of Surgery and Interventional Science, Centre for Nanotechnology and Regenerative Medicine, University College London, NW3 2PF London, United Kingdom
| | - Alexander M Seifalian
- Shima Salmasi, Deepak M Kalaskar, Alexander M Seifalian, UCL Division of Surgery and Interventional Science, Centre for Nanotechnology and Regenerative Medicine, University College London, NW3 2PF London, United Kingdom
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Tissue engineering of the temporomandibular joint disc: current status and future trends. Int J Artif Organs 2015; 38:55-68. [PMID: 25744198 DOI: 10.5301/ijao.5000393] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/18/2014] [Indexed: 11/20/2022]
Abstract
INTRODUCTION Temporomandibular joint disorders are extremely prevalent and there is no ideal treatment clinically for the moment. For severe cases, a discectomy often need to be performed, which will further result in the development of osteoarthritis. In the past thirty years, tissue engineering has provided a promising approach for the effective remedy of severe TMJ disease through the creation of viable, effective, and biological functional implants. METHODS Although TMJ disc tissue engineering is still in early stage, unremitting efforts and some achievements have been made over the past decades. In this review, a comprehensive summary of the available literature on the progress and status in tissue engineering of the TMJ disc regarding cell sources, scaffolds, biochemical and biomechanical stimuli, and other prospects relative to this field is provided. RESULTS AND CONCLUSIONS Even though research studies in this field are too few compared to other fibrocartilage (e.g., knee meniscus) and numerous, difficult tasks still exist, we believe that our ultimate goal of regenerating a biological implant whose histological, biochemical, and biomechanical properties parallel native TMJ discs for clinical therapy will be achieved in the near future.
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Abstract
Regenerative medicine is an alternative solution for organ transplantation. Stem cells and nanoscaffolds are two essential components in regenerative medicine. Mesenchymal stem cells (MSCs) are considered as primary adult stem cells with high proliferation capacity, wide differentiation potential, and immunosuppression properties which make them unique for regenerative medicine and cell therapy. Scaffolds are engineered nanofibers that provide suitable microenvironment for cell signalling which has a great influence on cell proliferation, differentiation, and biology. Recently, application of scaffolds and MSCs is being utilized in obtaining more homogenous population of MSCs with higher cell proliferation rate and greater differentiation potential, which are crucial factors in regenerative medicine. In this review, the definition, biology, source, characterization, and isolation of MSCs and current report of application of nanofibers in regenerative medicine in different lesions are discussed.
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Dash SN, Dash NR, Guru B, Mohapatra PC. Towards Reaching the Target: Clinical Application of Mesenchymal Stem Cells for Diabetic Foot Ulcers. Rejuvenation Res 2014; 17:40-53. [DOI: 10.1089/rej.2013.1467] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Affiliation(s)
| | - Nihar Ranjan Dash
- Department of Biochemistry, Apollo Hospitals Bhubaneswar, Odisha. India
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Titmarsh DM, Chen H, Glass NR, Cooper-White JJ. Concise review: microfluidic technology platforms: poised to accelerate development and translation of stem cell-derived therapies. Stem Cells Transl Med 2013; 3:81-90. [PMID: 24311699 DOI: 10.5966/sctm.2013-0118] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Stem cells are a powerful resource for producing a variety of cell types with utility in clinically associated applications, including preclinical drug screening and development, disease and developmental modeling, and regenerative medicine. Regardless of the type of stem cell, substantial barriers to clinical translation still exist and must be overcome to realize full clinical potential. These barriers span processes including cell isolation, expansion, and differentiation; purification, quality control, and therapeutic efficacy and safety; and the economic viability of bioprocesses for production of functional cell products. Microfluidic systems have been developed for a myriad of biological applications and have the intrinsic capability of controlling and interrogating the cellular microenvironment with unrivalled precision; therefore, they have particular relevance to overcoming such barriers to translation. Development of microfluidic technologies increasingly utilizes stem cells, addresses stem cell-relevant biological phenomena, and aligns capabilities with translational challenges and goals. In this concise review, we describe how microfluidic technologies can contribute to the translation of stem cell research outcomes, and we provide an update on innovative research efforts in this area. This timely convergence of stem cell translational challenges and microfluidic capabilities means that there is now an opportunity for both disciplines to benefit from increased interaction.
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Affiliation(s)
- Drew M Titmarsh
- Australian Institute for Bioengineering and Nanotechnology and
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