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Bilgili HK, Todoh M. Pioneering Soundscapes: Investigating Commercial Fused Deposition Modelling Filament's Potential for Ultrasound Technology in Bone Tissue Scaffolds. Bioengineering (Basel) 2025; 12:529. [PMID: 40428148 PMCID: PMC12108655 DOI: 10.3390/bioengineering12050529] [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: 04/01/2025] [Revised: 05/03/2025] [Accepted: 05/13/2025] [Indexed: 05/29/2025] Open
Abstract
Daily exposure to various forces creates defects in the musculoskeletal system, leading to health issues, especially for bones. Bone tissue scaffolds and ultrasound technology are both utilized in research and in clinics to enhance bone tissue regeneration. This study aimed to investigate the potential of commercially available fused deposition modeling (FDM) filaments for ultrasound technology using X-ray diffraction (XRD), Raman spectroscopy, nanoindentation, three-point bending, and scanning electron microscopy (SEM) characterization methods. Customized FDM filaments were produced by combining polylactic acid (PLA) FDM filaments with medical-grade polycaprolactone (PCL). Using these, we observed the successful production of complex tissue scaffolds via PLAPCL4060 and PLAPCL5050 FDM filaments. Additionally, the presence of the contrast difference observed via SEM for PLAPCL4060 suggests phase segregation and a material that has both damping and activating characteristics under ultrasound propagation. Mechanical characterization provided hardness and elastic modulus values, while the three-point bending results proved the flexible nature of PLAPCL4060 and PLAPCL5050, which is important for their dynamicity and responsiveness under ultrasound propagation. Accelerated degradation experiments provided crucial information regarding the effect of the porosity and gradients of scaffolds under ultrasound stimulation. Future studies based on this approach will contribute to understanding the true potential of these filaments for bone tissue.
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Affiliation(s)
- Hatice Kübra Bilgili
- Division of Human Mechanical Systems and Design, Graduate School of Engineering, Hokkaido University, Sapporo 060-8628, Japan
| | - Masahiro Todoh
- Division of Mechanical and Aerospace Engineering, Faculty of Engineering, Hokkaido University, Sapporo 060-8628, Japan;
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Martínez-Sanz E, Barrio-Asensio C, Maldonado E, Catón J, Arráez-Aybar LA, de Moraes LOC, López-Fernández P, Murillo-González J, Mérida-Velasco JR. Morphogenesis and functional aspects of the muscular layer of the middle deep cervical fascia in humans. Tissue Cell 2025; 93:102681. [PMID: 39705872 DOI: 10.1016/j.tice.2024.102681] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 12/08/2024] [Accepted: 12/10/2024] [Indexed: 12/23/2024]
Abstract
BACKGROUND In recent years, the fasciae of the human body have received significant attention because of their crucial role in the transmission of muscle force. However, studies on the development of the fasciae, particularly the cervical fascia, remain scarce. PURPOSE This study was performed to examine the development of the fascia of the infrahyoid strap muscles, also known as the middle layer of the deep cervical fascia (MDCF), in 17 human embryos aged 6-8 weeks and 20 human foetuses aged 9-14 weeks. METHODS Histological examination of serial sections was performed using conventional light microscopy. RESULTS Three stages in the development of the MDCF were identified: the initial, formation, and maturation stages. In the initial stage (week 6 of development, Carnegie stages 18-19), the mesenchymal primordium of the epimysium of the infrahyoid muscles was observed and found to be continuous with the mesenchymal primordium of the MDCF. The infrahyoid muscles already exhibited intramuscular fibres, the primordium of the perimysium, and the endomysium. In the formation stage (weeks 7-8 of development, Carnegie stages 20-23), fibroblast-like cells and collagen fibres appeared in the primordium of the muscle epimysium and in the MDCF. Intramuscular fibres had become very evident. In the maturation stage (from week 9 of development onward), further development and organisation of the fascial structures occurred. CONCLUSION Our results suggest that the MDCF of the neck develops in parallel with the mechanical activity of this region. The relationship between the MDCF and the lymphatic and venous structures of this region suggests that the MDCF may facilitate venous and lymphatic circulation.
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Affiliation(s)
- Elena Martínez-Sanz
- Department of Anatomy and Embryology, Faculty of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain; UCM Research Group No. 920202, Faculty of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain
| | - Carmen Barrio-Asensio
- UCM Research Group No. 920202, Faculty of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain; Department of Anatomy and Embryology, Faculty of Optics and Optometry, Universidad Complutense de Madrid (UCM), Madrid, Spain.
| | - Estela Maldonado
- Department of Anatomy and Embryology, Faculty of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain; UCM Research Group No. 920202, Faculty of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain
| | - Javier Catón
- Department of Anatomy and Embryology, Faculty of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain; UCM Research Group No. 920202, Faculty of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain
| | - Luis A Arráez-Aybar
- Department of Anatomy and Embryology, Faculty of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain; UCM Research Group No. 920202, Faculty of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain
| | - Luís Otávio Carvalho de Moraes
- Department of Morphology and Genetics, Discipline of Descriptive and Topographic Anatomy, Federal University of São Paulo, Brazil
| | - Pedro López-Fernández
- UCM Research Group No. 920202, Faculty of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain; General Surgery and Digestive System Service, Hospital Virgen de la Luz, Cuenca, Health Service of Castilla La Mancha, Spain
| | - Jorge Murillo-González
- Department of Anatomy and Embryology, Faculty of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain; UCM Research Group No. 920202, Faculty of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain
| | - José Ramón Mérida-Velasco
- Department of Anatomy and Embryology, Faculty of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain; UCM Research Group No. 920202, Faculty of Medicine, Universidad Complutense de Madrid (UCM), Madrid, Spain
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3
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de Wit RJJ, Tiemessen D, Oosterwijk E, Verhagen AFTM. Functional outcome of cell seeded tracheal scaffold after mechanical stress in vitro. BIOMATERIALS ADVANCES 2025; 167:214088. [PMID: 39536532 DOI: 10.1016/j.bioadv.2024.214088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 10/14/2024] [Accepted: 10/23/2024] [Indexed: 11/16/2024]
Abstract
Tracheal tissue engineering is still facing major challenges: realization of efficient vascularization and mechanical properties comparable to native trachea need to be achieved. In this study, we present a strategy for the manufacturing of a construct for tracheal tissue engineering by conditioning through cell seeding followed by mechanical stimulation in vitro. Scaffolds derived from porcine trachea decellularized with supercritical carbon dioxide were seeded with stem cells of different tissue sources and cultured in a bioreactor for 21 days under mechanical stimulation. Enhanced chondrogenic development was demonstrated, with improved sulphated glycosaminoglycan secretion and cellular alignment which resulted in mechanical properties resembling native trachea. This method may provide a useful addition to tracheal tissue engineering strategies aimed at optimizing cartilage formation.
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Affiliation(s)
- R J J de Wit
- Department of Cardio-thoracic surgery, Radboud University Medical Center, Geert Grooteplein 28, 6525 GE Nijmegen, the Netherlands.
| | - D Tiemessen
- Department of Urology, Radboud Institute for Molecular Life Science, Radboud University Medical Center, Geert Grooteplein 28, 6525 GE Nijmegen, the Netherlands
| | - E Oosterwijk
- Department of Urology, Radboud Institute for Molecular Life Science, Radboud University Medical Center, Geert Grooteplein 28, 6525 GE Nijmegen, the Netherlands
| | - A F T M Verhagen
- Department of Cardio-thoracic surgery, Radboud University Medical Center, Geert Grooteplein 28, 6525 GE Nijmegen, the Netherlands
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Tam KT, Baar K. Using load to improve tendon/ligament tissue engineering and develop novel treatments for tendinopathy. Matrix Biol 2025; 135:39-54. [PMID: 39645093 DOI: 10.1016/j.matbio.2024.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 11/15/2024] [Accepted: 12/01/2024] [Indexed: 12/09/2024]
Abstract
Tendon and ligament injuries are highly prevalent but heal poorly, even with proper care. Restoration of native tissue function is complicated by the fact that these tissues vary anatomically in terms of their mechanical properties, composition, and structure. These differences develop as adaptations to diverse mechanical demands; however, pathology may alter the loads placed on the tissue. Musculoskeletal loads can be generally categorized into tension, compression, and shear. Each of these regulate distinct molecular pathways that are involved in tissue remodeling, including many of the canonical tenogenic genes. In this review, we provide a perspective on the stage-specific regulation of mechanically sensitive pathways during development and maturation of tendon and ligament tissue, including scleraxis, mohawk, and others. Furthermore, we discuss structural features of healing and diseased tendon that may contribute to aberrant loading profiles, and how the associated disturbance in molecular signaling may contribute to incomplete healing or the formation of degenerative phenotypes. The perspectives provided here draw from studies spanning in vitro, animal, and human experiments of healthy and diseased tendon to propose a more targeted approach to advance rehabilitation, orthobiologics, and tissue engineering.
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Affiliation(s)
- Kenneth T Tam
- Biomedical Engineering Graduate Group, University of California Davis, Davis, CA 95616, USA; Department of Neurobiology, Physiology and Behavior, University of California Davis, Davis, CA 95616, USA
| | - Keith Baar
- Biomedical Engineering Graduate Group, University of California Davis, Davis, CA 95616, USA; Department of Neurobiology, Physiology and Behavior, University of California Davis, Davis, CA 95616, USA; Department of Physiology and Membrane Biology, University of California Davis, Davis, CA 95616, USA; VA Northern California Health Care System, Mather, CA 95655, USA.
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5
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Rashidi N, Harasymowicz NS, Savadipour A, Steward N, Tang R, Oswald S, Guilak F. PIEZO1-mediated mechanotransduction regulates collagen synthesis on nanostructured 2D and 3D models of fibrosis. Acta Biomater 2025; 193:242-254. [PMID: 39675497 DOI: 10.1016/j.actbio.2024.12.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 12/05/2024] [Accepted: 12/11/2024] [Indexed: 12/17/2024]
Abstract
Progressive fibrosis can lead to tissue malfunction and organ failure due to the pathologic accumulation of a collagen-rich extracellular matrix. In vitro models provide useful tools for deconstructing the roles of specific biomechanical or biological mechanisms, such as substrate micro- and nanoscale architecture, in these processes for identifying potential therapeutic targets. Here, we investigated how the mechanosensitive ion channel PIEZO1 influences fibrotic gene and protein expression in adipose-derived stem cells (hASCs). Specifically, we examined the role of PIEZO1 and the mechanosensitive transcription factors YAP/TAZ in sensing aligned or non-aligned substrate architecture to regulate collagen formation. We utilized both 2D microphotopatterned substrates and 3D electrospun polycaprolactone (PCL) substrates to study the role of culture dimensionality. We found that PIEZO1 regulates collagen synthesis in hASCs in a manner that is sensitive to substrate architecture. Activation of PIEZO1 induced significant morphological changes in hASCs, particularly when cultured on aligned substrates, leading to a 30-40 % reduction in cell spreading area and increased cell elongation, in 3D-aligned cultures. Picrosirius Red staining and immunoblotting revealed that PIEZO1 activation reduced collagen accumulation in 3D culture. While YAP translocated to the cytoplasm following PIEZO1 activation, depleting YAP and TAZ did not change collagen expression significantly downstream of PIEZO1 activation, implying that YAP/TAZ translocation from the nucleus and decreased collagen synthesis may be independent consequences of PIEZO1 activation. Our studies demonstrate a role for PIEZO1 in cellular mechanosensing of substrate architecture and provide targetable pathways for treating fibrosis and for enhancing tissue-engineered and regenerative approaches for fibrous tissue repair. STATEMENT OF SIGNIFICANCE: This study examines how cells sense and respond to their physical environment via PIEZO1 mechanotransduction. We discovered that cells use PIEZO1 to detect the alignment of surrounding structures, influencing the production of collagen - a key component in fibrosis. Our study used both 2D and 3D models to mimic different tissue environments, providing new insights into how cellular responses change in more complex settings. Importantly, we found that activating PIEZO1 alters cell shape and collagen production, especially on aligned surfaces. Interestingly, while PIEZO1 activation caused YAP translocation to the cytoplasm, this translocation did not directly affect collagen production. This work advances our understanding of fibrosis development and identifies PIEZO1 as a potential target for new therapies.
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Affiliation(s)
- Neda Rashidi
- Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA; Shriners Hospitals for Children, St. Louis, MO 63110, USA; Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Mechanical Engineering, Washington University, St. Louis, MO 63130, USA
| | - Natalia S Harasymowicz
- Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA; Shriners Hospitals for Children, St. Louis, MO 63110, USA; Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Alireza Savadipour
- Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA; Shriners Hospitals for Children, St. Louis, MO 63110, USA; Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Mechanical Engineering, Washington University, St. Louis, MO 63130, USA
| | - Nancy Steward
- Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA; Shriners Hospitals for Children, St. Louis, MO 63110, USA; Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Ruhang Tang
- Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA; Shriners Hospitals for Children, St. Louis, MO 63110, USA; Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Sara Oswald
- Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA; Shriners Hospitals for Children, St. Louis, MO 63110, USA; Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Farshid Guilak
- Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA; Shriners Hospitals for Children, St. Louis, MO 63110, USA; Center of Regenerative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Mechanical Engineering, Washington University, St. Louis, MO 63130, USA; Cytex Therapeutics, Inc., Durham, NC 27704, USA.
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Iorio F, El Khatib M, Wöltinger N, Turriani M, Di Giacinto O, Mauro A, Russo V, Barboni B, Boccaccini AR. Electrospun poly(ε-caprolactone)/poly(glycerol sebacate) aligned fibers fabricated with benign solvents for tendon tissue engineering. J Biomed Mater Res A 2025; 113:e37794. [PMID: 39295227 DOI: 10.1002/jbm.a.37794] [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: 04/16/2024] [Revised: 07/02/2024] [Accepted: 08/31/2024] [Indexed: 09/21/2024]
Abstract
The electrospinning technique is a commonly employed approach to fabricate fibers intended for various tissue engineering applications. The aim of this study is to develop a novel strategy for tendon repair through the use of aligned poly(ε-caprolactone) (PCL) and poly(glycerol sebacate) (PGS) fibers fabricated in benign solvents, and further explore the potential application of PGS in tendon tissue engineering (TTE). The fibers were characterized for their morphological and physicochemical properties; amniotic epithelial stem cells (AECs) were used to assess the fibers teno-inductive and immunomodulatory potential due to their ability to teno-differentiate undergoing first a stepwise epithelial to mesenchymal transition, and due to their documented therapeutic role in tendon regeneration. The addition of PGS to PCL improved the spinnability of the polymer solution, as well as the uniformity and directionality of the so-obtained fibers. The mechanical properties were in the range of most TTE applications, specifically in the case of PCL/PGS 4:1 and 2:1 ratios. Compared to PCL alone, the same ratios also allowed a better AECs infiltration and growth over 7 days of culture, and triggered the activation of tendon-related genes (SCX, COL1, TNMD) and the expression of tenomodulin (TNMD) at the protein level. Concerning the immunomodulatory properties, both PCL and PCL/PGS fibers negatively affected the immunomodulatory profile of AECs, up-regulating both anti-inflammatory (IL-10) and pro-inflammatory (IL-12) cytokines over 7 days of culture. Overall, PCL/PGS 2:1 fibers fabricated with benign solvents proved to be the most suitable composition for TTE application based on their topographical cues, mechanical properties, biocompatibility, and teno-inductive properties.
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Affiliation(s)
- Francesco Iorio
- Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Erlangen, Germany
- Department of Bioscience and Agro-Food and Environmental Technology, Unit of Basic and Applied Biosciences, University of Teramo, Teramo, Italy
| | - Mohammad El Khatib
- Department of Bioscience and Agro-Food and Environmental Technology, Unit of Basic and Applied Biosciences, University of Teramo, Teramo, Italy
| | - Natalie Wöltinger
- Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Erlangen, Germany
| | - Maura Turriani
- Department of Bioscience and Agro-Food and Environmental Technology, Unit of Basic and Applied Biosciences, University of Teramo, Teramo, Italy
| | - Oriana Di Giacinto
- Department of Bioscience and Agro-Food and Environmental Technology, Unit of Basic and Applied Biosciences, University of Teramo, Teramo, Italy
| | - Annunziata Mauro
- Department of Bioscience and Agro-Food and Environmental Technology, Unit of Basic and Applied Biosciences, University of Teramo, Teramo, Italy
| | - Valentina Russo
- Department of Bioscience and Agro-Food and Environmental Technology, Unit of Basic and Applied Biosciences, University of Teramo, Teramo, Italy
| | - Barbara Barboni
- Department of Bioscience and Agro-Food and Environmental Technology, Unit of Basic and Applied Biosciences, University of Teramo, Teramo, Italy
| | - Aldo R Boccaccini
- Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Erlangen, Germany
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Asadian E, Abbaszadeh S, Ghorbani-Bidkorpeh F, Rezaei S, Xiao B, Santos HA, Shahbazi MA. Hijacking plant skeletons for biomedical applications: from regenerative medicine and drug delivery to biosensing. Biomater Sci 2024; 13:9-92. [PMID: 39534968 DOI: 10.1039/d4bm00982g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
The field of biomedical engineering continually seeks innovative technologies to address complex healthcare challenges, ranging from tissue regeneration to drug delivery and biosensing. Plant skeletons offer promising opportunities for these applications due to their unique hierarchical structures, desirable porosity, inherent biocompatibility, and adjustable mechanical properties. This review comprehensively discusses chemical principles underlying the utilization of plant-based scaffolds in biomedical engineering. Highlighting their structural integrity, tunable properties, and possibility of chemical modification, the review explores diverse preparation strategies to tailor plant skeleton properties for bone, neural, cardiovascular, skeletal muscle, and tendon tissue engineering. Such applications stem from the cellulosic three-dimensional structure of different parts of plants, which can mimic the complexity of native tissues and extracellular matrices, providing an ideal environment for cell adhesion, proliferation, and differentiation. We also discuss the application of plant skeletons as carriers for drug delivery due to their structural diversity and versatility in encapsulating and releasing therapeutic agents with controlled kinetics. Furthermore, we present the emerging role played by plant-derived materials in biosensor development for diagnostic and monitoring purposes. Challenges and future directions in the field are also discussed, offering insights into the opportunities for future translation of sustainable plant-based technologies to address critical healthcare needs.
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Affiliation(s)
- Elham Asadian
- Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, 19689-17313, Tehran, Iran
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, 19689-17313, Tehran, Iran
| | - Samin Abbaszadeh
- Department of Pharmacology and Toxicology, School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran
| | - Fatemeh Ghorbani-Bidkorpeh
- Department of Pharmaceutics and Pharmaceutical Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saman Rezaei
- Department of Pharmacology and Toxicology, School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran
| | - Bo Xiao
- Personalized Drug Therapy Key Laboratory of Sichuan Province, Department of Pharmacy, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China.
| | - Hélder A Santos
- Department of Biomaterials and Biomedical Technology, The Personalized Medicine Research Institute (PRECISION), University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, Netherlands.
- Drug Research Program, Division of Pharmaceutical Chemistry and Technology, University of Helsinki, Helsinki FI-00014, Finland.
| | - Mohammad-Ali Shahbazi
- Department of Biomaterials and Biomedical Technology, The Personalized Medicine Research Institute (PRECISION), University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, Netherlands.
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Xiao Y, Yang S, Sun Y, Sah RL, Wang J, Han C. Nanoscale Morphologies on the Surface of Substrates/Scaffolds Enhance Chondrogenic Differentiation of Stem Cells: A Systematic Review of the Literature. Int J Nanomedicine 2024; 19:12743-12768. [PMID: 39634196 PMCID: PMC11615010 DOI: 10.2147/ijn.s492020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Accepted: 11/13/2024] [Indexed: 12/07/2024] Open
Abstract
Nanoscale morphologies on the surface of substrates/scaffolds have gained considerable attention in cartilage tissue engineering for their potential to improve chondrogenic differentiation and cartilage regeneration outcomes by mimicking the topographical and biophysical properties of the extracellular matrix (ECM). To evaluate the influence of nanoscale surface morphologies on chondrogenic differentiation of stem cells and discuss available strategies, we systematically searched evidence according to the PRISMA guidelines on PubMed, Embase, Web of Science, and Cochrane (until April 2024) and registered on the OSF (osf.io/3kvdb). The inclusion criteria were (in vitro) studies reporting the chondrogenic differentiation outcomes of nanoscale morphologies on the surface of substrates/scaffolds. The risk of bias (RoB) was assessed using the JBI-adapted quasi-experimental study assessment tool. Out of 1530 retrieved articles, 14 studies met the inclusion criteria. The evidence suggests that nanoholes, nanogrills, nanoparticles with a diameter of 10-40nm, nanotubes with a diameter of 70-100nm, nanopillars with a height of 127-330nm, and hexagonal nanostructures with a periodicity of 302-733nm on the surface of substrates/scaffolds result in better cell adhesion, growth, and chondrogenic differentiation of stem cells compared to the smooth/unpatterned ones through increasing integrin expression. Large nanoparticles with 300-1200nm diameter promote pre-chondrogenic cellular aggregation. The synergistic effects of the surface nanoscale topography and other environmental physical characteristics, such as matrix stiffness, also play important in the chondrogenic differentiation of stem cells. The RoB was low in 86% (12/14) of studies and high in 14% (2/14). Our study demonstrates that nanomorphologies with specific controlled properties engineered on the surface of substrates/scaffolds enhance stem cells' chondrogenic differentiation, which may benefit cartilage regeneration. However, given the variability in experimental designs and lack of reporting across studies, the results should be interpreted with caution.
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Affiliation(s)
- Yi Xiao
- Thoracic Surgery Department, The China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of China
- Orthopedic Medical Center, the Second Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of China
| | - Shiyan Yang
- Orthopedic Medical Center, the Second Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of China
- Department of Head and Neck, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China
| | - Yang Sun
- Orthopedic Medical Center, the Second Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of China
| | - Robert L Sah
- Department of Bioengineering, University of California–San Diego, La Jolla, CA, 92037, USA
- Center for Musculoskeletal Research, Institute of Engineering in Medicine, University of California–San Diego, La Jolla, CA, 92037, USA
| | - Jincheng Wang
- Orthopedic Medical Center, the Second Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of China
| | - Chunshan Han
- Thoracic Surgery Department, The China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of China
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9
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Lamont HC, Wright AL, Devries K, Okur KE, Jones M, Masood I, Hill LJ, Nazhat SN, Grover LM, Haj AJE, Metcalfe AD. Trabecular meshwork cell differentiation in response to collagen and TGFβ-2 spatial interactions. Acta Biomater 2024; 189:217-231. [PMID: 39218278 DOI: 10.1016/j.actbio.2024.08.046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 08/12/2024] [Accepted: 08/26/2024] [Indexed: 09/04/2024]
Abstract
Primary open-angle glaucoma (POAG) is currently the most prevalent cause of irreversible blindness globally. To date, few in vitro models that can faithfully recapitulate the complex architecture of the trabecular meshwork (TM) and the specialised trabecular meshwork cell (TMC) characteristics that are local to the structurally opposing regions. This study aimed to investigate the parameters that govern TMC phenotype by adapting the extracellular matrix structure to mimic the juxtacanalicular tissue (JCT) region of the TM. Initially, TMC phenotypic characteristics were investigated within type I collagen matrices of controlled fiber density and anisotropy, generated through confined plastic compression (PC). Notably, PC-collagen presented biophysical cues that induced JCT cellular characteristics (elastin, α-β-Crystallin protein expression, cytoskeletal remodelling, increased mesenchymal markers and JCT-specific genetic markers). In parallel, a pathological mesenchymal phenotype associated with POAG was induced through localised transforming growth factor -beta 2 (TGFβ-2) exposure. This resulted in a profile of alternative mesenchymal states (fibroblast/smooth muscle or myofibroblast) displayed by the TMC in vitro. Overall, the study provides an advanced insight into the biophysical cues that modulate TMC fate, inducing a JCT-specific phenotype and transient mesenchymal characteristics that reflect healthy and pathological scenarios. STATEMENT OF SIGNIFICANCE: Glaucoma is a leading cause of blindness, with a lack of long-term efficacy within current drug candidates. Reliable trabecular meshwork (TM) in vitro models will be critical for enhancing the fields understanding of healthy and disease states for pre-clinical testing. Trabecular meshwork cells (TMCs) display heterogeneity throughout the hierarchical TM, however our understanding into recapitulating these phenotypes in vitro, remains elusive. This study hypothesizes the importance of specific matrix/growth factor spatial stimuli in governing TMCs phenotype. By emulating certain biophysical/biochemical in vivo parameters, we introduce an advanced profile of distinct TMC phenotypic states, reflecting healthy and disease scenarios. A notion that has not be stated prior and a fundamental consideration for future 3D TM in vitro modelling.
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Affiliation(s)
- Hannah C Lamont
- Healthcare Technologies Institute, School of Chemical Engineering, University of Birmingham, Birmingham, UK.
| | - Abigail L Wright
- Healthcare Technologies Institute, School of Chemical Engineering, University of Birmingham, Birmingham, UK
| | - Kate Devries
- Department of Mining and Materials Engineering, McGill University, Canada
| | - Kerime E Okur
- Healthcare Technologies Institute, School of Chemical Engineering, University of Birmingham, Birmingham, UK
| | - Michael Jones
- Cell Guidance Systems Ltd, Maia Building, Babraham Bioscience Campus, Cambridge, UK
| | - Imran Masood
- School of Biomedical Sciences, Institute of Clinical Sciences, University of Birmingham, UK
| | - Lisa J Hill
- School of Biomedical Sciences, Institute of Clinical Sciences, University of Birmingham, UK
| | - Showan N Nazhat
- Department of Mining and Materials Engineering, McGill University, Canada
| | - Liam M Grover
- Healthcare Technologies Institute, School of Chemical Engineering, University of Birmingham, Birmingham, UK
| | - Alicia J El Haj
- Healthcare Technologies Institute, School of Chemical Engineering, University of Birmingham, Birmingham, UK
| | - Anthony D Metcalfe
- Healthcare Technologies Institute, School of Chemical Engineering, University of Birmingham, Birmingham, UK
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10
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Lin S, Reisdorf R, Lu CK, Wang Z, An KN, Moran SL, Amadio PC, Zhao C. Cell-based tissue engineered flexor tendon allograft: A canine in vivo study. J Orthop Res 2024; 42:1923-1932. [PMID: 38639414 PMCID: PMC11293999 DOI: 10.1002/jor.25854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 01/31/2024] [Accepted: 03/30/2024] [Indexed: 04/20/2024]
Abstract
This study aimed to compare the clinically established autologous extrasynovial tendon graft to a newly developed tissue-engineered allograft (Eng-allograft) in terms of functional outcomes following flexor tendon reconstruction in a canine model. The second and fifth flexor digitorum profundus (FDP) tendons from 16 dogs were transected and repaired in Zone II. After 6 weeks of cage activity, the repaired tendons were intentionally ruptured, creating a clinically relevant model for reconstruction. The re-ruptured FDP tendons were then reconstructed using either the clinically standard autologous extrasynovial tendon graft or the Eng-allograft, which had been revitalized with autologous bone marrow-derived mesenchymal stem cells (BMSCs) and synovialized using carbodiimide derivatized synovial fluid (cd-SYN). Following 12 weeks of postoperative rehabilitation, the functional outcomes of the surgical digits were evaluated. The Eng-allograft group exhibited improved digital function, including lower digit work of flexion and reduced adhesion status, while maintaining similar tendon gliding resistance compared to the autograft group. However, the failure load of both the distal and proximal host/graft conjunctions in the Eng-allograft group was significantly lower than that of the autograft group with higher graft rupture at the host-graft junction. In conclusion, the decellularized allogenic intrasynovial tendon, when revitalized BMSCs and synovialized with cd-SYN, demonstrates positive effects on digital function improvement and adhesion reduction. However, the healing at both proximal and distal graft/host junctions is far lower than the autograft. Further research is needed to enhance the healing capacity of allograft conjunctions, aiming to achieve a comparable level of healing seen with autografts.
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Affiliation(s)
- Subin Lin
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
- Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P.R. China
| | - Ramona Reisdorf
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Chun Kuan Lu
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Zhanwen Wang
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Kai-Nan An
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Steven L. Moran
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Peter C. Amadio
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Chunfeng Zhao
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA
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11
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Haidar-Montes AA, Mauro A, El Khatib M, Prencipe G, Pierdomenico L, Tosi U, Wouters G, Cerveró-Varona A, Berardinelli P, Russo V, Barboni B. Mechanobiological Strategies to Enhance Ovine ( Ovis aries) Adipose-Derived Stem Cells Tendon Plasticity for Regenerative Medicine and Tissue Engineering Applications. Animals (Basel) 2024; 14:2233. [PMID: 39123758 PMCID: PMC11310997 DOI: 10.3390/ani14152233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 07/28/2024] [Accepted: 07/29/2024] [Indexed: 08/12/2024] Open
Abstract
Adipose-derived stem cells (ADSCs) hold promise for tendon repair, even if their tenogenic plasticity and underlying mechanisms remain only partially understood, particularly in cells derived from the ovine animal model. This study aimed to characterize oADSCs during in vitro expansion to validate their phenotypic properties pre-transplantation. Moreover, their tenogenic potential was assessed using two in vitro-validated approaches: (1) teno-inductive conditioned media (CM) derived from a co-culture between ovine amniotic stem cells and fetal tendon explants, and (2) short- (48 h) and long-term (14 days) seeding on highly aligned PLGA (ha-PLGA) electrospun scaffold. Our findings indicate that oADSCs can be expanded without senescence and can maintain the expression of stemness (Sox2, Oct4, Nanog) and mesenchymal (CD29, CD166, CD44, CD90) markers while remaining negative for hematopoietic (CD31, CD45) and MHC-II antigens. Of note, oADSCs' tendon differentiation potential greatly depended on the in vitro strategy. oADSCs exposed to CM significantly upregulated tendon-related genes (COL1, TNMD, THBS4) but failed to accumulate TNMD protein at 14 days of culture. Conversely, oADSCs seeded on ha-PLGA fleeces quickly upregulated the tendon-related genes (48 h) and in 14 days accumulated high levels of the TNMD protein into the cytoplasm of ADSCs, displaying a tenocyte-like morphology. This mechano-sensing cellular response involved a complete SOX9 downregulation accompanied by YAP activation, highlighting the efficacy of biophysical stimuli in promoting tenogenic differentiation. These findings underscore oADSCs' long-term self-renewal and tendon differentiative potential, thus opening their use in a preclinical setting to develop innovative stem cell-based and tissue engineering protocols for tendon regeneration, applied to the veterinary field.
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Affiliation(s)
- Arlette A. Haidar-Montes
- Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy; (A.A.H.-M.); (M.E.K.); (G.P.); (U.T.); (A.C.-V.); (P.B.); (V.R.); (B.B.)
| | - Annunziata Mauro
- Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy; (A.A.H.-M.); (M.E.K.); (G.P.); (U.T.); (A.C.-V.); (P.B.); (V.R.); (B.B.)
| | - Mohammad El Khatib
- Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy; (A.A.H.-M.); (M.E.K.); (G.P.); (U.T.); (A.C.-V.); (P.B.); (V.R.); (B.B.)
| | - Giuseppe Prencipe
- Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy; (A.A.H.-M.); (M.E.K.); (G.P.); (U.T.); (A.C.-V.); (P.B.); (V.R.); (B.B.)
| | - Laura Pierdomenico
- Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy;
| | - Umberto Tosi
- Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy; (A.A.H.-M.); (M.E.K.); (G.P.); (U.T.); (A.C.-V.); (P.B.); (V.R.); (B.B.)
| | - Guy Wouters
- FAT STEM Company, Erembodegem, 9300 Aalst, Belgium;
| | - Adrián Cerveró-Varona
- Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy; (A.A.H.-M.); (M.E.K.); (G.P.); (U.T.); (A.C.-V.); (P.B.); (V.R.); (B.B.)
| | - Paolo Berardinelli
- Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy; (A.A.H.-M.); (M.E.K.); (G.P.); (U.T.); (A.C.-V.); (P.B.); (V.R.); (B.B.)
| | - Valentina Russo
- Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy; (A.A.H.-M.); (M.E.K.); (G.P.); (U.T.); (A.C.-V.); (P.B.); (V.R.); (B.B.)
| | - Barbara Barboni
- Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy; (A.A.H.-M.); (M.E.K.); (G.P.); (U.T.); (A.C.-V.); (P.B.); (V.R.); (B.B.)
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12
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Xu Y, Yao Y, Gao J. Cell-Derived Matrix: Production, Decellularization, and Application of Wound Repair. Stem Cells Int 2024; 2024:7398473. [PMID: 38882595 PMCID: PMC11178417 DOI: 10.1155/2024/7398473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 04/25/2024] [Accepted: 05/17/2024] [Indexed: 06/18/2024] Open
Abstract
Chronic nonhealing wounds significantly reduce patients' quality of life and are a major burden on healthcare systems. Over the past few decades, tissue engineering materials have emerged as a viable option for wound healing, with cell-derived extracellular matrix (CDM) showing remarkable results. The CDM's compatibility and resemblance to the natural tissue microenvironment confer distinct advantages to tissue-engineered scaffolds in wound repair. This review summarizes the current processes for CDM preparation, various cell decellularization protocols, and common characterization methods. Furthermore, it discusses the applications of CDM in wound healing, including skin defect and wound repair, angiogenesis, and engineered vessels, and offers perspectives on future developments.
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Affiliation(s)
- Yidan Xu
- Department of Plastic and Cosmetic Surgery Nanfang Hospital Southern Medical University, 1838 Guangzhou North Road, Guangzhou 510515, Guangdong, China
| | - Yao Yao
- Department of Plastic and Cosmetic Surgery Nanfang Hospital Southern Medical University, 1838 Guangzhou North Road, Guangzhou 510515, Guangdong, China
| | - Jianhua Gao
- Department of Plastic and Cosmetic Surgery Nanfang Hospital Southern Medical University, 1838 Guangzhou North Road, Guangzhou 510515, Guangdong, China
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13
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Abhari RE, Snelling SJ, Augustynak E, Davis S, Fischer R, Carr AJ, Mouthuy PA. A Hybrid Electrospun-Extruded Polydioxanone Suture for Tendon Tissue Regeneration. Tissue Eng Part A 2024; 30:214-224. [PMID: 38126344 PMCID: PMC10954604 DOI: 10.1089/ten.tea.2023.0273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Accepted: 11/13/2023] [Indexed: 12/23/2023] Open
Abstract
Many surgical tendon repairs fail despite advances in surgical materials and techniques. Tendon repair failure can be partially attributed to the tendon's poor intrinsic healing capacity and the repurposing of sutures from other clinical applications. Electrospun materials show promise as a biological scaffold to support endogenous tendon repair, but their relatively low tensile strength has limited their clinical translation. It is hypothesized that combining electrospun fibers with a material with increased tensile strength may improve the suture's mechanical properties while retaining biophysical cues necessary to encourage cell-mediated repair. This article describes the production of a hybrid electrospun-extruded suture with a sheath of submicron electrospun fibers and a core of melt-extruded fibers. The porosity and tensile strength of this hybrid suture is compared with an electrospun-only braided suture and clinically used sutures Vicryl and polydioxanone (PDS). Bioactivity is assessed by measuring the adsorbed serum proteins on electrospun and melt-extruded filaments using mass spectrometry. Human hamstring tendon fibroblast attachment and proliferation were quantified and compared between the hybrid and control sutures. Combining an electrospun sheath with melt-extruded cores created a hybrid braid with increased tensile strength (70.1 ± 0.3N) compared with an electrospun only suture (12.9 ± 1 N, p < 0.0001). The hybrid suture had a similar force at break to clinical sutures, but lower stiffness and stress. The Young's modulus was 772.6 ± 32 MPa for the hybrid suture, 1693.0 ± 69 MPa for PDS, and 3838.0 ± 132 MPa for Vicryl, p < 0.0001. Hybrid sutures had lower overall porosity than electrospun-only sutures (40 ± 4% and 60 ± 7%, respectively, p = 0.0018) but had a significantly larger overall porosity and average pore diameter compared with surgical sutures. There were similar clusters of adsorbed proteins on electrospun and melt-extruded filaments, which were distinct from PDS. Tendon fibroblast attachment and cell proliferation on hybrid and electrospun sutures were significantly higher than on clinical sutures. This study demonstrated that a bioactive suture with increased tensile strength and lower stiffness could be produced by adding a core of 10 μm melt-extruded fibers to a sheath of electrospun fibers. In contrast to currently used sutures, the hybrid sutures promoted a bioactive response: serum proteins adsorbed, and fibroblasts attached, survived, grew along the sutures, and adopted appropriate morphologies.
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Affiliation(s)
- Roxanna E. Abhari
- Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom
| | - Sarah J.B. Snelling
- Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom
| | - Edyta Augustynak
- Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom
| | - Simon Davis
- Nuffield Department of Medicine, Target Discovery Institute, Centre for Medicines Discovery, University of Oxford, Oxford, United Kingdom
- Nuffield Department of Medicine, Chinese Academy for Medical Sciences Oxford Institute, University of Oxford, Oxford, United Kingdom
| | - Roman Fischer
- Nuffield Department of Medicine, Target Discovery Institute, Centre for Medicines Discovery, University of Oxford, Oxford, United Kingdom
- Nuffield Department of Medicine, Chinese Academy for Medical Sciences Oxford Institute, University of Oxford, Oxford, United Kingdom
| | - Andrew J. Carr
- Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom
| | - Pierre-Alexis Mouthuy
- Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom
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14
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Couvrette LJ, Walker KLA, Bui TV, Pelling AE. Plant Cellulose as a Substrate for 3D Neural Stem Cell Culture. Bioengineering (Basel) 2023; 10:1309. [PMID: 38002433 PMCID: PMC10669287 DOI: 10.3390/bioengineering10111309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 10/06/2023] [Accepted: 11/01/2023] [Indexed: 11/26/2023] Open
Abstract
Neural stem cell (NSC)-based therapies are at the forefront of regenerative medicine strategies for various neural defects and injuries such as stroke, traumatic brain injury, and spinal cord injury. For several clinical applications, NSC therapies require biocompatible scaffolds to support cell survival and to direct differentiation. Here, we investigate decellularized plant tissue as a novel scaffold for three-dimensional (3D), in vitro culture of NSCs. Plant cellulose scaffolds were shown to support the attachment and proliferation of adult rat hippocampal neural stem cells (NSCs). Further, NSCs differentiated on the cellulose scaffold had significant increases in their expression of neuron-specific beta-III tubulin and glial fibrillary acidic protein compared to 2D culture on a polystyrene plate, indicating that the scaffold may enhance the differentiation of NSCs towards astrocytic and neuronal lineages. Our findings suggest that plant-derived cellulose scaffolds have the potential to be used in neural tissue engineering and can be harnessed to direct the differentiation of NSCs.
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Affiliation(s)
- Lauren J. Couvrette
- Department of Biology, University of Ottawa, Gendron Hall, 30 Marie Curie, Ottawa, ON K1N 5N5, Canada
| | - Krystal L. A. Walker
- Department of Physics, University of Ottawa, STEM Complex, 150 Louis Pasteur Pvt., Ottawa, ON K1N 5N5, Canada
| | - Tuan V. Bui
- Department of Biology, University of Ottawa, Gendron Hall, 30 Marie Curie, Ottawa, ON K1N 5N5, Canada
| | - Andrew E. Pelling
- Department of Biology, University of Ottawa, Gendron Hall, 30 Marie Curie, Ottawa, ON K1N 5N5, Canada
- Department of Physics, University of Ottawa, STEM Complex, 150 Louis Pasteur Pvt., Ottawa, ON K1N 5N5, Canada
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15
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Lewis M, David G, Jacobs D, Kuczwara P, Woessner AE, Kim JW, Quinn KP, Song Y. Neuro-regenerative behavior of adipose-derived stem cells in aligned collagen I hydrogels. Mater Today Bio 2023; 22:100762. [PMID: 37600354 PMCID: PMC10433000 DOI: 10.1016/j.mtbio.2023.100762] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2023] [Revised: 07/16/2023] [Accepted: 08/04/2023] [Indexed: 08/22/2023] Open
Abstract
Peripheral nerve injuries persist as a major clinical issue facing the US population and can be caused by stretch, laceration, or crush injuries. Small nerve gaps are simple to treat, and the nerve stumps can be reattached with sutures. In longer nerve gaps, traditional treatment options consist of autografts, hollow nerve guidance conduits, and, more recently, manufactured fibrous scaffolds. These manufactured scaffolds often incorporate stem cells, growth factors, and/or extracellular matrix (ECM) proteins to better mimic the native environment but can have issues with homogenous cell distribution or uniformly oriented neurite outgrowth in scaffolds without fibrous alignment. Here, we utilize a custom device to fabricate collagen I hydrogels with aligned fibers and encapsulated adipose-derived mesenchymal stem cells (ASCs) for potential use as a peripheral nerve repair graft. Initial results of our scaffold system revealed significantly less cell viability in higher collagen gel concentrations; 3 mg/mL gels showed 84.8 ± 7.3% viable cells, compared to 6 mg/mL gels viability of 76.7 ± 9.5%. Mechanical testing of the 3 mg/mL gels showed a Young's modulus of 6.5 ± 0.8 kPa nearly matching 7.45 kPa known to support Schwann cell migration. Further analysis of scaffolds coupled with stretching in vitro revealed heightened angiogenic and factor secretion, ECM deposition, fiber alignment, and dorsal root ganglia (DRG) neurite outgrowth along the axis of fiber alignment. Our platform serves as an in vitro testbed to assess neuro-regenerative potential of ASCs in aligned collagen fiber scaffolds and may provide guidance on next-generation nerve repair scaffold design.
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Affiliation(s)
- Mackenzie Lewis
- Department of Biomedical Engineering; University of Arkansas, Fayetteville, AR, USA
| | - Gabriel David
- Department of Biomedical Engineering; University of Arkansas, Fayetteville, AR, USA
| | - Danielle Jacobs
- Department of Biomedical Engineering; University of Arkansas, Fayetteville, AR, USA
| | - Patrick Kuczwara
- Department of Biomedical Engineering; University of Arkansas, Fayetteville, AR, USA
- Department of Biological & Agricultural Engineering; University of Arkansas, Fayetteville, AR, USA
| | - Alan E. Woessner
- Department of Biomedical Engineering; University of Arkansas, Fayetteville, AR, USA
| | - Jin-Woo Kim
- Department of Biological & Agricultural Engineering; University of Arkansas, Fayetteville, AR, USA
- Materials Science & Engineering Program; University of Arkansas, Fayetteville, AR, USA
| | - Kyle P. Quinn
- Department of Biomedical Engineering; University of Arkansas, Fayetteville, AR, USA
| | - Younghye Song
- Department of Biomedical Engineering; University of Arkansas, Fayetteville, AR, USA
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16
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Son YH, Yang DH, Uricoli B, Park SJ, Jeong GJ, Chun HJ. Three-Dimensional Cell Culture System for Tendon Tissue Engineering. Tissue Eng Regen Med 2023; 20:553-562. [PMID: 37278865 PMCID: PMC10313620 DOI: 10.1007/s13770-023-00550-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 04/07/2023] [Accepted: 05/01/2023] [Indexed: 06/07/2023] Open
Abstract
Tendon, connective tissue between bone and muscle has unique component of the musculoskeletal system. It plays important role for transporting mechanical stress from muscle to bone and enabling locomotive motion of the body. There are some restoration capacities in the tendon tissue, but the injured tendons are not completely regenerated after acute and chronic tendon injury. At this point, the treatment options for tendon injuries are limited and not that successful. Therefore, biomedical engineering approaches are emerged to cope with this issue. Among them, three-dimensional cell culture platforms provided similarity to in vivo conditions and suggested opportunities for new therapeutic approaches for treatment of tendon injuries. In this review, we focus on the characteristics of tendon tissue and tendon pathologies which can be targets for tendon tissue engineering strategies. Then proof-of-concept and pre-clinical studies leveraging advanced 3-dimensional cell culture platforms for tendon tissue regeneration have been discussed.
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Affiliation(s)
- Young Hoon Son
- Biohybrid Systems Group, Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University School of Medicine, Atlanta, GA, 30322, USA
| | - Dae Hyeok Yang
- Institute of Cell and Tissue Engineering, College of Medicine, The Catholic University of Korea, Seoul, 06591, the Republic of Korea
| | - Biaggio Uricoli
- Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University School of Medicine, Atlanta, GA, 30322, USA
| | - Sung-Jin Park
- Biohybrid Systems Group, Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Emory University School of Medicine, Atlanta, GA, 30322, USA
| | - Gun-Jae Jeong
- Institute of Cell and Tissue Engineering, College of Medicine, The Catholic University of Korea, Seoul, 06591, the Republic of Korea.
| | - Heung Jae Chun
- Institute of Cell and Tissue Engineering, College of Medicine, The Catholic University of Korea, Seoul, 06591, the Republic of Korea.
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17
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Freedman BR, Hwang C, Talbot S, Hibler B, Matoori S, Mooney DJ. Breakthrough treatments for accelerated wound healing. SCIENCE ADVANCES 2023; 9:eade7007. [PMID: 37196080 PMCID: PMC10191440 DOI: 10.1126/sciadv.ade7007] [Citation(s) in RCA: 134] [Impact Index Per Article: 67.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Accepted: 04/14/2023] [Indexed: 05/19/2023]
Abstract
Skin injuries across the body continue to disrupt everyday life for millions of patients and result in prolonged hospital stays, infection, and death. Advances in wound healing devices have improved clinical practice but have mainly focused on treating macroscale healing versus underlying microscale pathophysiology. Consensus is lacking on optimal treatment strategies using a spectrum of wound healing products, which has motivated the design of new therapies. We summarize advances in the development of novel drug, biologic products, and biomaterial therapies for wound healing for marketed therapies and those in clinical trials. We also share perspectives for successful and accelerated translation of novel integrated therapies for wound healing.
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Affiliation(s)
- Benjamin R. Freedman
- John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
- Beth Israel Deaconess Medical Center, Department of Orthopaedic Surgery, Boston, MA, USA
| | - Charles Hwang
- Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard University, Boston, MA, USA
| | - Simon Talbot
- Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard University, Boston, MA, USA
| | | | - Simon Matoori
- John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
- Faculty of Pharmacy, University of Montreal, Montreal, QC, Canda
| | - David J. Mooney
- John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
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18
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Griffanti G, McKee MD, Nazhat SN. Mineralization of Bone Extracellular Matrix-like Scaffolds Fabricated as Silk Sericin-Functionalized Dense Collagen–Fibrin Hybrid Hydrogels. Pharmaceutics 2023; 15:pharmaceutics15041087. [PMID: 37111573 PMCID: PMC10142947 DOI: 10.3390/pharmaceutics15041087] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 03/20/2023] [Accepted: 03/22/2023] [Indexed: 03/31/2023] Open
Abstract
The design of hydrogels that combine both the biochemical cues needed to direct seeded cellular functions and mineralization to provide the structural and mechanical properties approaching those of mineralized native bone extracellular matrix (ECM) represents a significant challenge in bone tissue engineering. While fibrous hydrogels constituting of collagen or fibrin (and their hybrids) can be considered as scaffolds that mimic to some degree native bone ECM, their insufficient mechanical properties limit their application. In the present study, an automated gel aspiration–ejection (automated GAE) method was used to generate collagen–fibrin hybrid gel scaffolds with micro-architectures and mechanical properties approaching those of native bone ECM. Moreover, the functionalization of these hybrid scaffolds with negatively charged silk sericin accelerated their mineralization under acellular conditions in simulated body fluid and modulated the proliferation and osteoblastic differentiation of seeded MC3T3-E1 pre-osteoblastic cells. In the latter case, alkaline phosphatase activity measurements indicated that the hybrid gel scaffolds with seeded cells showed accelerated osteoblastic differentiation, which in turn led to increased matrix mineralization. In summary, the design of dense collagen–fibrin hybrid gels through an automated GAE process can provide a route to tailoring specific biochemical and mechanical properties to different types of bone ECM-like scaffolds, and can provide a model to better understand cell–matrix interactions in vitro for bioengineering purposes.
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Affiliation(s)
- Gabriele Griffanti
- Department of Mining and Materials Engineering, McGill University, Montréal, QC H3A 0C5, Canada;
| | - Marc D. McKee
- Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montréal, QC H3A 0C7, Canada;
- Department of Anatomy and Cell Biology, McGill University, Montréal, QC H3A 0C7, Canada
| | - Showan N. Nazhat
- Department of Mining and Materials Engineering, McGill University, Montréal, QC H3A 0C5, Canada;
- Correspondence: ; Tel.: +514-398-5524; Fax: 514-398-4492
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19
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Hu J, Liu S, Fan C. Applications of functionally-adapted hydrogels in tendon repair. Front Bioeng Biotechnol 2023; 11:1135090. [PMID: 36815891 PMCID: PMC9934866 DOI: 10.3389/fbioe.2023.1135090] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Accepted: 01/23/2023] [Indexed: 02/05/2023] Open
Abstract
Despite all the efforts made in tissue engineering for tendon repair, the management of tendon injuries still poses a challenge, as current treatments are unable to restore the function of tendons following injuries. Hydrogels, due to their exceptional biocompatibility and plasticity, have been extensively applied and regarded as promising candidate biomaterials in tissue regeneration. Varieties of approaches have designed functionally-adapted hydrogels and combined hydrogels with other factors (e.g., bioactive molecules or drugs) or materials for the enhancement of tendon repair. This review first summarized the current state of knowledge on the mechanisms underlying the process of tendon healing. Afterward, we discussed novel strategies in fabricating hydrogels to overcome the issues frequently encountered during the applications in tendon repair, including poor mechanical properties and undesirable degradation. In addition, we comprehensively summarized the rational design of hydrogels for promoting stem-cell-based tendon tissue engineering via altering biophysical and biochemical factors. Finally, the role of macrophages in tendon repair and how they respond to immunomodulatory hydrogels were highlighted.
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Affiliation(s)
- Jiacheng Hu
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai, China
| | - Shen Liu
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai, China
| | - Cunyi Fan
- Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration, Shanghai, China
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Zhang Q, Liu Y, Li J, Wang J, Liu C. Recapitulation of growth factor-enriched microenvironment via BMP receptor activating hydrogel. Bioact Mater 2023; 20:638-650. [PMID: 35846838 PMCID: PMC9270210 DOI: 10.1016/j.bioactmat.2022.06.012] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 05/31/2022] [Accepted: 06/15/2022] [Indexed: 11/18/2022] Open
Abstract
Exposure to a growth factor abundant milieu has remarkable regenerative and rejuvenating effects on organ diseases, tissue damage, and regeneration, including skeletal system defects and bone regeneration. Although the introduction of candidate growth factors into relevant fields has been reported, their regenerative effects remain unsatisfactory, mainly because of the experimental challenges with limited types of growth factors, elusive dosage adjustment, and asynchronous stem cell activation with cytokine secretion. Here, an innovative hydrogel recapitulating a growth factor-enriched microenvironment (GEM) for regenerative advantage, is reported. This sulfated hydrogel includes bone morphogenetic protein-2 (BMP-2), an essential growth factor in osteogenesis, to direct mesenchymal stem cell (MSC) differentiation, stimulate cell proliferation, and improve bone formation. The semi-synthetic hydrogel, sulfonated gelatin (S-Gelatin), can amplify BMP-2 signaling in mouse MSCs by enhancing the binding between BMP-2 and BMP-2 type II receptors (BMPR2), which are located on MSC nuclei and activated by the hydrogel. Importantly, the dramatically improved cytokine secretion of MSCs throughout regeneration confirms the growth factor-acquiring potential of S-Gelatin/rhBMP-2 hydrogel, leading to the vascularization enhancement. These findings provide a new strategy to achieve an in situ GEM and accelerated bone regeneration by amplifying the regenerative capacity of rhBMP-2 and capturing endogenous growth factors.
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Affiliation(s)
- Qinghao Zhang
- Material Science and Engineering School, East China University of Science and Technology, Shanghai, 200237, PR China
- Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China
- Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China
- Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Meilong Road 130, Shanghai, 200237, PR China
| | - Yuanda Liu
- Material Science and Engineering School, East China University of Science and Technology, Shanghai, 200237, PR China
- Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China
- Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China
- Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Meilong Road 130, Shanghai, 200237, PR China
| | - Jie Li
- Material Science and Engineering School, East China University of Science and Technology, Shanghai, 200237, PR China
- Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China
- Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China
- Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Meilong Road 130, Shanghai, 200237, PR China
| | - Jing Wang
- Material Science and Engineering School, East China University of Science and Technology, Shanghai, 200237, PR China
- Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China
- Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China
- The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, PR China
| | - Changsheng Liu
- Material Science and Engineering School, East China University of Science and Technology, Shanghai, 200237, PR China
- Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China
- Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China
- Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, Meilong Road 130, Shanghai, 200237, PR China
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21
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Tindell RK, Busselle LP, Holloway JL. Magnetic fields enable precise spatial control over electrospun fiber alignment for fabricating complex gradient materials. J Biomed Mater Res A 2023; 111:778-789. [PMID: 36594559 DOI: 10.1002/jbm.a.37492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Revised: 12/14/2022] [Accepted: 12/16/2022] [Indexed: 01/04/2023]
Abstract
Musculoskeletal interfacial tissues consist of complex gradients in structure, cell phenotype, and biochemical signaling that are important for function. Designing tissue engineering strategies to mimic these types of gradients is an ongoing challenge. In particular, new fabrication techniques that enable precise spatial control over fiber alignment are needed to better mimic the structural gradients present in interfacial tissues, such as the tendon-bone interface. Here, we report a modular approach to spatially controlling fiber alignment using magnetically-assisted electrospinning. Electrospun fibers were highly aligned in the presence of a magnetic field and smoothly transitioned to randomly aligned fibers away from the magnetic field. Importantly, magnetically-assisted electrospinning allows for spatial control over fiber alignment at sub-millimeter resolution along the length of the fibrous scaffold similar to the native structural gradient present in many interfacial tissues. The versatility of this approach was further demonstrated using multiple electrospinning polymers and different magnet configurations to fabricate complex fiber alignment gradients. As expected, cells seeded onto gradient fibrous scaffolds were elongated and aligned on the aligned fibers and did not show a preferential alignment on the randomly aligned fibers. Overall, this fabrication approach represents an important step forward in creating gradient fibrous materials, where such materials are promising as tissue-engineered scaffolds for regenerating functional musculoskeletal interfacial tissues.
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Affiliation(s)
- Raymond Kevin Tindell
- Chemical Engineering, School of Engineering of Matter, Transport and Energy, Arizona State University, Tempe, Arizona, USA
| | - Lincoln P Busselle
- Chemical Engineering, School of Engineering of Matter, Transport and Energy, Arizona State University, Tempe, Arizona, USA
| | - Julianne L Holloway
- Chemical Engineering, School of Engineering of Matter, Transport and Energy, Arizona State University, Tempe, Arizona, USA
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22
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Ghuloum FI, Johnson CA, Riobo-Del Galdo NA, Amer MH. From mesenchymal niches to engineered in vitro model systems: Exploring and exploiting biomechanical regulation of vertebrate hedgehog signalling. Mater Today Bio 2022; 17:100502. [PMID: 36457847 PMCID: PMC9707069 DOI: 10.1016/j.mtbio.2022.100502] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Revised: 11/08/2022] [Accepted: 11/20/2022] [Indexed: 11/23/2022] Open
Abstract
Tissue patterning is the result of complex interactions between transcriptional programs and various mechanical cues that modulate cell behaviour and drive morphogenesis. Vertebrate Hedgehog signalling plays key roles in embryogenesis and adult tissue homeostasis, and is central to skeletal development and the osteogenic differentiation of mesenchymal stem cells. The expression of several components of the Hedgehog signalling pathway have been reported to be mechanically regulated in mesodermal tissue patterning and osteogenic differentiation in response to external stimulation. Since a number of bone developmental defects and skeletal diseases, such as osteoporosis, are directly linked to aberrant Hedgehog signalling, a better knowledge of the regulation of Hedgehog signalling in the mechanosensitive bone marrow-residing mesenchymal stromal cells will present novel avenues for modelling these diseases and uncover novel opportunities for extracellular matrix-targeted therapies. In this review, we present a brief overview of the key molecular players involved in Hedgehog signalling and the basic concepts of mechanobiology, with a focus on bone development and regeneration. We also highlight the correlation between the activation of the Hedgehog signalling pathway in response to mechanical cues and osteogenesis in bone marrow-derived mesenchymal stromal cells. Finally, we propose different tissue engineering strategies to apply the expanding knowledge of 3D material-cell interactions in the modulation of Hedgehog signalling in vitro for fundamental and translational research applications.
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Affiliation(s)
- Fatmah I. Ghuloum
- School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom
- Department of Biological Sciences, Faculty of Science, Kuwait University, Kuwait City, Kuwait
| | - Colin A. Johnson
- Leeds Institute of Medical Research, Faculty of Medicine and Health, University of Leeds, Leeds, UK
| | - Natalia A. Riobo-Del Galdo
- School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom
- Leeds Institute of Medical Research, Faculty of Medicine and Health, University of Leeds, Leeds, UK
- Astbury Centre for Structural Molecular Biology, University of Leeds, UK
| | - Mahetab H. Amer
- School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom
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23
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Elango J, Lijnev A, Zamora-Ledezma C, Alexis F, Wu W, Marín JMG, Sanchez de Val JEM. The Relationship of Rheological Properties and the Performance of Silk Fibroin Hydrogels in Tissue Engineering Application. Process Biochem 2022. [DOI: 10.1016/j.procbio.2022.12.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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24
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Brudnicki PAP, Gonsalves MA, Spinella SM, Kaufman LJ, Lu HH. Engineering collagenous analogs of connective tissue extracellular matrix. Front Bioeng Biotechnol 2022; 10:925838. [PMID: 36312546 PMCID: PMC9613959 DOI: 10.3389/fbioe.2022.925838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 07/07/2022] [Indexed: 11/17/2022] Open
Abstract
Connective tissue extracellular matrix (ECM) consists of an interwoven network of contiguous collagen fibers that regulate cell activity, direct biological function, and guide tissue homeostasis throughout life. Recently, ECM analogs have emerged as a unique ex vivo culture platform for studying healthy and diseased tissues and in the latter, enabling the screening for and development of therapeutic regimen. Since these tissue models can mitigate the concern that observations from animal models do not always translate clinically, the design and production of a collagenous ECM analogue with relevant chemistry and nano- to micro-scale architecture remains a frontier challenge in the field. Therefore, the objectives of this study are two-fold— first, to apply green electrospinning approaches to the fabrication of an ECM analog with nanoscale mimicry and second, to systematically optimize collagen crosslinking in order to produce a stable, collagen-like substrate with continuous fibrous architecture that supports human cell culture and phenotypic expression. Specifically, the “green” electrospinning solvent acetic acid was evaluated for biofabrication of gelatin-based meshes, followed by the optimization of glutaraldehyde (GTA) crosslinking under controlled ambient conditions. These efforts led to the production of a collagen-like mesh with nano- and micro-scale cues, fibrous continuity with little batch-to-batch variability, and proven stability in both dry and wet conditions. Moreover, the as-fabricated mesh architecture and native chemistry were preserved with augmented mechanical properties. These meshes supported the in vitro expansion of stem cells and the production of a mineralized matrix by human osteoblast-like cells. Collectively these findings demonstrate the potential of green fabrication in the production of a collagen-like ECM analog with physiological relevance. Future studies will explore the potential of this high-fidelity platform for elucidating cell-matrix interactions and their relevance in connective tissue healing.
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Affiliation(s)
- Philip A. P. Brudnicki
- Biomaterials and Interface Tissue Engineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY, United States
| | - Matthew A. Gonsalves
- Biomaterials and Interface Tissue Engineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY, United States
| | | | - Laura J. Kaufman
- Department of Chemistry, Columbia University, New York, NY, United States
| | - Helen H. Lu
- Biomaterials and Interface Tissue Engineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY, United States
- *Correspondence: Helen H. Lu,
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25
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Wen SM, Wen WC, Chao PHG. Zyxin and actin structure confer anisotropic YAP mechanotransduction. Acta Biomater 2022; 152:313-320. [PMID: 36089236 DOI: 10.1016/j.actbio.2022.08.079] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 08/24/2022] [Accepted: 08/31/2022] [Indexed: 11/01/2022]
Abstract
Tissues and the embedded cells experience anisotropic deformations due to their functions and anatomical locations. The resident cells, such as tenocytes and muscle cells, are often restricted by their extracellular matrix and organize parallel to their major loading direction, yet most studies on cellular responses to strains use isotropic substrates without predetermined organizations. To understand how confined cells sense and respond to anisotropic loading, we combine cell patterning and uniaxial stretch to have precise geometric control. Dynamic stretch parallel to the long axis of the cell activates YAP nuclear translocation, but not when stretched in the perpendicular direction. Looking at the initial cytoskeleton response, parallel stretch leads to actin breakage and repair within the first minute, mediated by zyxin, the focal adhesion protein. In addition, this zyxin-mediated repair response is controlled by focal adhesion kinase (FAK) and leads to YAP signaling. As these factors are intimately involved in a wide range of mechanical regulation, our findings point to new roles of zyxin and YAP in anisotropic mechanotransduction, and may provide additional perspectives in cellular adaptive responses and tissue homeostasis. STATEMENT OF SIGNIFICANCE: Structure and deformation of tissues control gene expression, migration, and proliferation of the resident cells. In an effort to understand the underlying mechanisms, we find that the transcription cofactor YAP respond to mechanical stretch in a direction-dependent manner. We demonstrate that parallel stretch induces actin cytoskeleton damage, focal adhesion kinase (FAK) activation, and zyxin relocation, which are involved in the anisotropic YAP signaling. Our findings provide additional perspectives in the interactions of tissue structure and cell mechanotransduction.
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Affiliation(s)
- Shin-Min Wen
- Department of Biomedical Engineering, School of Medicine and School of Engineering National Taiwan University
| | - Wen-Cih Wen
- Department of Biomedical Engineering, School of Medicine and School of Engineering National Taiwan University
| | - Pen-Hsiu Grace Chao
- Department of Biomedical Engineering, School of Medicine and School of Engineering National Taiwan University.
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26
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Abstract
Approved therapies for tendon diseases have not yet changed the clinical practice of symptomatic pain treatment and physiotherapy. This review article summarizes advances in the development of novel drugs, biologic products, and biomaterial therapies for tendon diseases with perspectives for translation of integrated therapies. Shifting from targeting symptom relief toward disease modification and prevention of disease progression may open new avenues for therapies. Deep evidence-based clinical, cellular, and molecular characterization of the underlying pathology of tendon diseases, as well as therapeutic delivery optimization and establishment of multidiscipline interorganizational collaboration platforms, may accelerate the discovery and translation of transformative therapies for tendon diseases.
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Affiliation(s)
- Benjamin R. Freedman
- John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA
| | - David J. Mooney
- John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA
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27
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Lu L, Zhang J, Guan K, Zhou J, Yuan F, Guan Y. Artificial neural network for cytocompatibility and antibacterial enhancement induced by femtosecond laser micro/nano structures. J Nanobiotechnology 2022; 20:365. [PMID: 35933376 PMCID: PMC9357338 DOI: 10.1186/s12951-022-01578-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 07/25/2022] [Indexed: 01/04/2023] Open
Abstract
The failure of orthopedic and dental implants is mainly caused by biomaterial-associated infections and poor osseointegration. Surface modification of biomedical materials plays a significant role in enhancing osseointegration and anti-bacterial infection. In this work, a non-linear relationship between the micro/nano surface structures and the femtosecond laser processing parameters was successfully established based on an artificial neural network. Then a controllable functional surface with silver nanoparticles (AgNPs) to was produced to improve the cytocompatibility and antibacterial properties of biomedical titanium alloy. The surface topography, wettability, and Ag+ release were carefully investigated. The effects of these characteristics on antibacterial activity and cytocompatibilty were also evaluated. Results show that the prepared surface is hydrophobic, which can prevent the burst release of Ag+ in the initial stage. The prepared surface also shows both good cytocompatibility toward the murine calvarial preosteoblasts MC3T3-E1 cells (derived from Mus musculus (mouse) calvaria) and good antibacterial effects against Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria, which is caused by the combined effect of appropriate micro/nano-structured feature and reasonable Ag+ release rate. We do not only clarify the antibacterial mechanism but also demonstrate the possibility of balancing the antibacterial and osteointegration-promoting properties by micro/nano-structures. The reported method offers an effective strategy for the patterned surface modification of implants.
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Affiliation(s)
- Libin Lu
- Advanced Manufacturing Center, Ningbo Institute of Technology, Beihang University, Ningbo, 315100, China
| | - Jiaru Zhang
- School of Mechanical Engineering & Automation, Beihang University, Beijing, 100083, China
| | - Kai Guan
- Department of Radiotherapy, The Third Hospital of Zhangzhou City, Zhangzhou, 363005, Fujian, China
| | - Jin Zhou
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, China.
| | - Fusong Yuan
- National Center of Stomatology & National Clinical Research Center for Oral Diseases, Beijing, 100081, China
| | - Yingchun Guan
- Advanced Manufacturing Center, Ningbo Institute of Technology, Beihang University, Ningbo, 315100, China. .,School of Mechanical Engineering & Automation, Beihang University, Beijing, 100083, China. .,National Engineering Laboratory of Additive Manufacturing for Large Metallic Components, Beihang University, 37 Xueyuan Road, Beijing, 100083, China.
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28
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Zhang Y, Habibovic P. Delivering Mechanical Stimulation to Cells: State of the Art in Materials and Devices Design. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2022; 34:e2110267. [PMID: 35385176 DOI: 10.1002/adma.202110267] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 03/19/2022] [Indexed: 06/14/2023]
Abstract
Biochemical signals, such as growth factors, cytokines, and transcription factors are known to play a crucial role in regulating a variety of cellular activities as well as maintaining the normal function of different tissues and organs. If the biochemical signals are assumed to be one side of the coin, the other side comprises biophysical cues. There is growing evidence showing that biophysical signals, and in particular mechanical cues, also play an important role in different stages of human life ranging from morphogenesis during embryonic development to maturation and maintenance of tissue and organ function throughout life. In order to investigate how mechanical signals influence cell and tissue function, tremendous efforts have been devoted to fabricating various materials and devices for delivering mechanical stimuli to cells and tissues. Here, an overview of the current state of the art in the design and development of such materials and devices is provided, with a focus on their design principles, and challenges and perspectives for future research directions are highlighted.
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Affiliation(s)
- Yonggang Zhang
- Department of Instructive Biomaterials Engineering, Maastricht University, MERLN Institute for Technology-Inspired Regenerative Medicine, Universiteitssingel 40, Maastricht, 6229 ER, The Netherlands
| | - Pamela Habibovic
- Department of Instructive Biomaterials Engineering, Maastricht University, MERLN Institute for Technology-Inspired Regenerative Medicine, Universiteitssingel 40, Maastricht, 6229 ER, The Netherlands
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29
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Donderwinkel I, Tuan RS, Cameron NR, Frith JE. Tendon tissue engineering: Current progress towards an optimized tenogenic differentiation protocol for human stem cells. Acta Biomater 2022; 145:25-42. [PMID: 35470075 DOI: 10.1016/j.actbio.2022.04.028] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 04/10/2022] [Accepted: 04/18/2022] [Indexed: 12/19/2022]
Abstract
Tendons are integral to our daily lives by allowing movement and locomotion but are frequently injured, leading to patient discomfort and impaired mobility. Current clinical procedures are unable to fully restore the native structure of the tendon, resulting in loss of full functionality, and the weakened tissue following repair often re-ruptures. Tendon tissue engineering, involving the combination of cells with biomaterial scaffolds to form new tendon tissue, holds promise to improve patient outcomes. A key requirement for efficacy in promoting tendon tissue formation is the optimal differentiation of the starting cell populations, most commonly adult tissue-derived mesenchymal stem/stromal cells (MSCs), into tenocytes, the predominant cellular component of tendon tissue. Currently, a lack of consensus on the protocols for effective tenogenic differentiation is hampering progress in tendon tissue engineering. In this review, we discuss the current state of knowledge regarding human stem cell differentiation towards tenocytes and tendon tissue formation. Tendon development and healing mechanisms are described, followed by a comprehensive overview of the current protocols for tenogenic differentiation, including the effects of biochemical and biophysical cues, and their combination, on tenogenesis. Lastly, a synthesis of the key features of these protocols is used to design future approaches. The holistic evaluation of current knowledge should facilitate and expedite the development of efficacious stem cell tenogenic differentiation protocols with future impact in tendon tissue engineering. STATEMENT OF SIGNIFICANCE: The lack of a widely-adopted tenogenic differentiation protocol has been a major hurdle in the tendon tissue engineering field. Building on current knowledge on tendon development and tendon healing, this review surveys peer-reviewed protocols to present a holistic evaluation and propose a pathway to facilitate and expedite the development of a consensus protocol for stem cell tenogenic differentiation and tendon tissue engineering.
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30
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Özkale B, Lou J, Özelçi E, Elosegui-Artola A, Tringides CM, Mao AS, Sakar MS, Mooney DJ. Actuated 3D microgels for single cell mechanobiology. LAB ON A CHIP 2022; 22:1962-1970. [PMID: 35437554 PMCID: PMC10116575 DOI: 10.1039/d2lc00203e] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/03/2023]
Abstract
We present a new cell culture technology for large-scale mechanobiology studies capable of generating and applying optically controlled uniform compression on single cells in 3D. Mesenchymal stem cells (MSCs) are individually encapsulated inside an optically triggered nanoactuator-alginate hybrid biomaterial using microfluidics, and the encapsulating network isotropically compresses the cell upon activation by light. The favorable biomolecular properties of alginate allow cell culture in vitro up to a week. The mechanically active microgels are capable of generating up to 15% compressive strain and forces reaching 400 nN. As a proof of concept, we demonstrate the use of the mechanically active cell culture system in mechanobiology by subjecting singly encapsulated MSCs to optically generated isotropic compression and monitoring changes in intracellular calcium intensity.
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Affiliation(s)
- Berna Özkale
- Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA.
- Wyss Institute for Biologically Inspired Engineering, Cambridge, MA, 02138, USA
| | - Junzhe Lou
- Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA.
- Wyss Institute for Biologically Inspired Engineering, Cambridge, MA, 02138, USA
| | - Ece Özelçi
- Institute of Mechanical Engineering and Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015, Lausanne, Switzerland.
| | - Alberto Elosegui-Artola
- Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA.
- Wyss Institute for Biologically Inspired Engineering, Cambridge, MA, 02138, USA
| | - Christina M Tringides
- Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA.
- Wyss Institute for Biologically Inspired Engineering, Cambridge, MA, 02138, USA
| | - Angelo S Mao
- Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA.
- Wyss Institute for Biologically Inspired Engineering, Cambridge, MA, 02138, USA
| | - Mahmut Selman Sakar
- Institute of Mechanical Engineering and Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015, Lausanne, Switzerland.
| | - David J Mooney
- Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA.
- Wyss Institute for Biologically Inspired Engineering, Cambridge, MA, 02138, USA
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31
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Guo X, Wang X, Tang H, Ren Y, Li D, Yi B, Zhang Y. Engineering a Mechanoactive Fibrous Substrate with Enhanced Efficiency in Regulating Stem Cell Tenodifferentiation. ACS APPLIED MATERIALS & INTERFACES 2022; 14:23219-23231. [PMID: 35544769 DOI: 10.1021/acsami.2c04294] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Electrospun-aligned fibers in ultrathin fineness have previously demonstrated a limited capacity in driving stem cells to differentiate into tendon-like cells. In view of the tendon's mechanoactive nature, endowing such aligned fibrous structure with mechanoactivity to exert in situ mechanical stimulus by itself, namely, without any forces externally applied, is likely to potentiate its efficiency of tenogenic induction. To test this hypothesis, in this study, a shape-memory-capable poly(l-lactide-co-caprolactone) (PLCL) copolymer was electrospun into aligned fibrous form followed by a "stretching-recovery" shape-programming procedure to impart shape memory capability. Thereafter, in the absence of tenogenic supplements, human adipose-derived stem cells (ADSCs) were cultured on the programmed fibrous substrates for a duration of 7 days, and the effects of constrained recovery resultant stress-stiffening on cell morphology, proliferation, and tenogenic differentiation were examined. The results indicate that the in situ enacted mechanical stimulus due to shape memory effect (SME) did not have adverse influence on cell viability and proliferation, but significantly promoted cellular elongation along the direction of fiber alignment. Moreover, it revealed that tendon-specific protein markers such as tenomodulin (TNMD) and tenascin-C (TNC) and gene expression of scleraxis (SCX), TNMD, TNC, and collagen I (COL I) were significantly upregulated on the mechanoactive fibrous substrate with higher recovery stress compared to the counterparts. Mechanistically, the Rho/ROCK signaling pathway was identified to be involved in the substrate self-actuation-induced enhancement in tenodifferentiation. Together, these results suggest that constrained shape recovery stress may be employed as an innovative loading modality to regulate the stem cell tenodifferentiation by presenting the fibrous substrate with an aligned tendon-like topographical cue and an additional mechanoactivity. This newly demonstrated paradigm in modulating stem cell tenodifferentiation may improve the efficacy of tendon tissue engineering strategy for tendon healing and regeneration.
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Affiliation(s)
- Xuran Guo
- College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China
- Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, Donghua University, Shanghai 201620, China
| | - Xianliu Wang
- College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China
- Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, Donghua University, Shanghai 201620, China
| | - Han Tang
- College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China
- Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, Donghua University, Shanghai 201620, China
| | - Yajuan Ren
- Longhua Hospital affiliated to the Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Donghong Li
- College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China
- Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, Donghua University, Shanghai 201620, China
| | - Bingcheng Yi
- College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China
- Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital affiliated to the Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Yanzhong Zhang
- College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China
- Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, Donghua University, Shanghai 201620, China
- Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital affiliated to the Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
- China Orthopedic Regenerative Medicine Group (CORMed), Hangzhou 310058, China
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32
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Direct Conversion of Bovine Dermal Fibroblasts into Myotubes by Viral Delivery of Transcription Factor bMyoD. APPLIED SCIENCES-BASEL 2022. [DOI: 10.3390/app12094688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Direct reprogramming of somatic cells to myoblasts and myotubes holds great potential for muscle development, disease modeling and regenerative medicine. According to recent studies, direct conversion of fibroblasts to myoblasts was performed by using a transcription factor, myoblast determination protein (MyoD), which belongs to a family of myogenic regulatory factors. Therefore, MyoD is considered to be a key driver in the generation of induced myoblasts. In this study, we compared the direct phenotypic conversion of bovine dermal fibroblasts (BDFs) into myoblasts and myotubes by supplementing a transcription factor, bovine MyoD (bMyoD), in the form of recombinant protein or the bMyoD gene, through retroviral vectors. As a result, the delivery of the bMyoD gene to BDFs was more efficient for inducing reprogramming, resulting in direct conversion to myoblasts and myotubes, when compared with protein delivery. BDFs cultured with retrovirus encoding bMyoD increased myogenic gene expression, such as MyoG, MYH3 and MYMK. In addition, the cells expressed myoblast or myotube-specific marker proteins, MyoG and Desmin, respectively. Our findings provide an informative tool for the myogenesis of domestic-animal-derived somatic cells via transgenic technology. By using this method, a new era of regenerative medicine and cultured meat is expected.
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Qiu J, Ahn J, Qin D, Thomopoulos S, Xia Y. Biomimetic Scaffolds with a Mineral Gradient and Funnel-Shaped Channels for Spatially Controllable Osteogenesis. Adv Healthc Mater 2022; 11:e2100828. [PMID: 34050610 DOI: 10.1002/adhm.202100828] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 05/15/2021] [Indexed: 12/14/2022]
Abstract
A facile method is described herein for generating a mineral gradient in a biodegradable polymer scaffold. The gradient is achieved by swelling a composite film made of polycaprolactone (PCL) and hydroxyapatite (HAp) nanoparticles with a PCL solution. During the swelling process, the solvent and PCL polymer chains diffuse into the composite film, generating a gradient in HAp density at their interface. The thickness of the mineral gradient can be tuned by varying the extent of swelling to match the length scale of the natural tendon-to-bone attachment (20-60 µm). When patterned with an array of funnel-shaped channels, the mineral gradient presents stem cells with spatial gradations in both biochemical cues (e.g., osteoinductivity and conductivity associated with the HAp nanoparticles) and mechanical cues (e.g., substrate stiffness) to stimulate their differentiation into a graded distribution of cell phenotypes. This new class of biomimetic scaffolds holds great promise for facilitating the regeneration of the injured tendon-to-bone attachment by stimulating the formation of a functionally graded interface.
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Affiliation(s)
- Jichuan Qiu
- The Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University Atlanta GA 30332 USA
| | - Jaewan Ahn
- School of Materials Science and Engineering Georgia Institute of Technology Atlanta GA 30332 USA
| | - Dong Qin
- School of Materials Science and Engineering Georgia Institute of Technology Atlanta GA 30332 USA
| | - Stavros Thomopoulos
- Department of Orthopedic Surgery Department of Biomedical Engineering Columbia University New York NY 10032 USA
| | - Younan Xia
- The Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology and Emory University Atlanta GA 30332 USA
- School of Chemistry and Biochemistry School of Chemical and Biomolecular Engineering Georgia Institute of Technology Atlanta GA 30332 USA
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Alsmairat O, Barakat N. Characterizing the Effect of Adding Boron Nitride Nanotubes on the Mechanical Properties of Electrospun Polymer Nanocomposite Microfibers Mesh. MATERIALS (BASEL, SWITZERLAND) 2022; 15:1634. [PMID: 35268874 PMCID: PMC8911170 DOI: 10.3390/ma15051634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 02/11/2022] [Accepted: 02/15/2022] [Indexed: 02/04/2023]
Abstract
Electrospun fibrous meshes have a variety of applications such as filtration, drug delivery, energy storage, and engineered tissues due to their high surface area to mass ratio. Therefore, understanding the mechanical properties of these continuously evolving meshes is critical to expand and improve their performance. In this study, the effect of adding Boron Nitride Nanotube (BNNT) to Polymethylmethacrylate (PMMA) composite meshes on the mechanical properties of the polymer is studied. Electrospinning is used to fabricate microfiber meshes of PMMA and BNNT-PMMA. The fabricated meshes are tested experimentally with a uniaxial tensile tester. In addition, a theoretical model is introduced to investigate the effect of the number of fibers and the diameter of fiber inside the mesh on Young's Modulus and Tensile Strength of the PMMA mesh. By adding 0.5% BNNT to the PMMA, Young's Modulus and Tensile Strength of the PMMA mesh improved by 62.4% and 9.3%, respectively. Furthermore, simulated results show enhanced mesh properties when increasing the number of fibers and the single fiber diameter inside the mesh. The findings of this study help in understanding the mechanical properties of the nanocomposite electrospun meshes which expands and improves its utilization in different applications.
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Affiliation(s)
- Ohood Alsmairat
- Department of Mechanical Engineering, The University of Texas at Tyler, 3900 University Blvd., Tyler, TX 75799, USA;
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Ambattu LA, Gelmi A, Yeo LY. Short-Duration High Frequency MegaHertz-Order Nanomechanostimulation Drives Early and Persistent Osteogenic Differentiation in Mesenchymal Stem Cells. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2022; 18:e2106823. [PMID: 35023629 DOI: 10.1002/smll.202106823] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Revised: 12/12/2021] [Indexed: 06/14/2023]
Abstract
Stem cell fate can be directed through the application of various external physical stimuli, enabling a controlled approach to targeted differentiation. Studies involving the use of dynamic mechanical cues driven by vibrational excitation to date have, however, been limited to low frequency (Hz to kHz) forcing over extended durations (typically continuous treatment for >7 days). Contrary to previous assertions that there is little benefit in applying frequencies beyond 1 kHz, we show here that high frequency MHz-order mechanostimulation in the form of nanoscale amplitude surface reflected bulk waves are capable of triggering differentiation of human mesenchymal stem cells from various donor sources toward an osteoblast lineage, with early, short time stimuli inducing long-term osteogenic commitment. More specifically, rapid treatments (10 min daily over 5 days) of the high frequency (10 MHz) mechanostimulation are shown to trigger significant upregulation in early osteogenic markers (RUNX2, COL1A1) and sustained increase in late markers (osteocalcin, osteopontin) through a mechanistic pathway involving piezo channel activation and Rho-associated protein kinase signaling. Given the miniaturizability and low cost of the devices, the possibility for upscaling the platform toward practical bioreactors, to address a pressing need for more efficient stem cell differentiation technologies in the pursuit of translatable regenerative medicine strategies, is ensivaged.
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Affiliation(s)
- Lizebona August Ambattu
- Micro/Nanophysics Research Laboratory, School of Engineering, RMIT University, Melbourne, Victoria, 3000, Australia
| | - Amy Gelmi
- School of Science, RMIT University, Melbourne, Victoria, 3000, Australia
| | - Leslie Y Yeo
- Micro/Nanophysics Research Laboratory, School of Engineering, RMIT University, Melbourne, Victoria, 3000, Australia
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Kim EM, Lee GM, Lee S, Kim SJ, Lee D, Yoon DS, Joo J, Kong H, Park HH, Shin H. Effects of mechanical properties of gelatin methacryloyl hydrogels on encapsulated stem cell spheroids for 3D tissue engineering. Int J Biol Macromol 2022; 194:903-913. [PMID: 34838857 DOI: 10.1016/j.ijbiomac.2021.11.145] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 11/18/2021] [Accepted: 11/22/2021] [Indexed: 01/22/2023]
Abstract
Cell spheroids are three-dimensional cell aggregates that have been widely employed in tissue engineering. Spheroid encapsulation has been explored as a method to enhance cell-cell interactions. However, the effect of hydrogel mechanical properties on spheroids, specifically soft hydrogels (<1 kPa), has not yet been studied. In this study, we determined the effect of encapsulation of stem cell spheroids by hydrogels crosslinked with different concentrations of gelatin methacryloyl (GelMA) on the functions of the stem cells. To this end, human adipose-derived stem cell (ADSC) spheroids with a defined size were prepared, and spheroid-laden hydrogels with various concentrations (5, 10, 15%) were fabricated. The apoptotic index of cells from spheroids encapsulated in the 15% hydrogel was high. The migration distance was five-fold higher in cells encapsulated in the 5% hydrogel than the 10% hydrogel. After 14 days of culture, cells from spheroids in the 5% hydrogel were observed to have spread and proliferated. Osteogenic factor and pro-angiogenic factor production in the 15% hydrogel was high. Collectively, our results indicate that the functionality of spheroids can be regulated by the mechanical properties of hydrogel, even under 1 kPa. These results indicate that spheroid-laden hydrogels are suitable for use in 3D tissue construction.
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Affiliation(s)
- Eun Mi Kim
- Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea
| | - Gyeong Min Lee
- Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 FOUR Education and Research Group for Biopharmaceutical Innovation Leader, Department of Bioengineering, College of Engineering, Hanyang University, Republic of Korea
| | - Sangmin Lee
- Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 FOUR Education and Research Group for Biopharmaceutical Innovation Leader, Department of Bioengineering, College of Engineering, Hanyang University, Republic of Korea
| | - Se-Jeong Kim
- Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 FOUR Education and Research Group for Biopharmaceutical Innovation Leader, Department of Bioengineering, College of Engineering, Hanyang University, Republic of Korea
| | - Dongtak Lee
- School of Biomedical Engineering, Korea University, Seoul 20841, Republic of Korea
| | - Dae Sung Yoon
- School of Biomedical Engineering, Korea University, Seoul 20841, Republic of Korea
| | - Jinmyoung Joo
- Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
| | - Hyunjoon Kong
- Department of Chemical and Biomolecular engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States
| | - Hee Ho Park
- Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea.
| | - Heungsoo Shin
- Department of Bioengineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea; BK21 FOUR Education and Research Group for Biopharmaceutical Innovation Leader, Department of Bioengineering, College of Engineering, Hanyang University, Republic of Korea; Institute of Nano Science and Technology, Hanyang University, 222 Wangsimri-ro, Seongdong-gu, Seoul 04763, Republic of Korea.
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Cao H, Duan L, Zhang Y, Cao J, Zhang K. Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity. Signal Transduct Target Ther 2021; 6:426. [PMID: 34916490 PMCID: PMC8674418 DOI: 10.1038/s41392-021-00830-x] [Citation(s) in RCA: 439] [Impact Index Per Article: 109.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 11/10/2021] [Accepted: 11/11/2021] [Indexed: 02/05/2023] Open
Abstract
Hydrogel is a type of versatile platform with various biomedical applications after rational structure and functional design that leverages on material engineering to modulate its physicochemical properties (e.g., stiffness, pore size, viscoelasticity, microarchitecture, degradability, ligand presentation, stimulus-responsive properties, etc.) and influence cell signaling cascades and fate. In the past few decades, a plethora of pioneering studies have been implemented to explore the cell-hydrogel matrix interactions and figure out the underlying mechanisms, paving the way to the lab-to-clinic translation of hydrogel-based therapies. In this review, we first introduced the physicochemical properties of hydrogels and their fabrication approaches concisely. Subsequently, the comprehensive description and deep discussion were elucidated, wherein the influences of different hydrogels properties on cell behaviors and cellular signaling events were highlighted. These behaviors or events included integrin clustering, focal adhesion (FA) complex accumulation and activation, cytoskeleton rearrangement, protein cyto-nuclei shuttling and activation (e.g., Yes-associated protein (YAP), catenin, etc.), cellular compartment reorganization, gene expression, and further cell biology modulation (e.g., spreading, migration, proliferation, lineage commitment, etc.). Based on them, current in vitro and in vivo hydrogel applications that mainly covered diseases models, various cell delivery protocols for tissue regeneration and disease therapy, smart drug carrier, bioimaging, biosensor, and conductive wearable/implantable biodevices, etc. were further summarized and discussed. More significantly, the clinical translation potential and trials of hydrogels were presented, accompanied with which the remaining challenges and future perspectives in this field were emphasized. Collectively, the comprehensive and deep insights in this review will shed light on the design principles of new biomedical hydrogels to understand and modulate cellular processes, which are available for providing significant indications for future hydrogel design and serving for a broad range of biomedical applications.
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Affiliation(s)
- Huan Cao
- Department of Nuclear Medicine, West China Hospital, and National Engineering Research Center for Biomaterials, Sichuan University, 610064, Chengdu, P. R. China
- Department of Medical Ultrasound and Central Laboratory, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301 Yan-chang-zhong Road, 200072, Shanghai, People's Republic of China
- School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore
| | - Lixia Duan
- Department of Medical Ultrasound and Central Laboratory, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301 Yan-chang-zhong Road, 200072, Shanghai, People's Republic of China
| | - Yan Zhang
- Department of Medical Ultrasound and Central Laboratory, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301 Yan-chang-zhong Road, 200072, Shanghai, People's Republic of China
| | - Jun Cao
- Department of Nuclear Medicine, West China Hospital, and National Engineering Research Center for Biomaterials, Sichuan University, 610064, Chengdu, P. R. China.
| | - Kun Zhang
- Department of Medical Ultrasound and Central Laboratory, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301 Yan-chang-zhong Road, 200072, Shanghai, People's Republic of China.
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Zhou H, Piñeiro Llanes J, Sarntinoranont M, Subhash G, Simmons CS. Label-free quantification of soft tissue alignment by polarized Raman spectroscopy. Acta Biomater 2021; 136:363-374. [PMID: 34537413 DOI: 10.1016/j.actbio.2021.09.015] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 08/24/2021] [Accepted: 09/09/2021] [Indexed: 11/29/2022]
Abstract
The organization of proteins is an important determinant of functionality in soft tissues. However, such organization is difficult to monitor over time in soft tissue with complex compositions. Here, we establish a method to determine the alignment of proteins in soft tissues of varying composition by polarized Raman spectroscopy (PRS). Unlike most conventional microscopy methods, PRS leverages non-destructive, label-free sample preparation. PRS data from highly aligned muscle layers were utilized to derive a weighting function for aligned proteins via principal component analysis (PCA). This trained weighting function was used as a master loading function to calculate a principal component score (PC1 Score) as a function of polarized angle for tendon, dermis, hypodermis, and fabricated collagen gels. Since the PC1 Score calculated at arbitrary angles was insufficient to determine level of alignment, we developed an Amplitude Alignment Metric by fitting a sine function to PC1 Score with respect to polarized angle. We found that our PRS-based Amplitude Alignment Metric can be used as an indicator of level of protein alignment in soft tissues in a non-destructive manner with label-free preparation and has similar discriminatory capacity among isotropic and anisotropic samples compared to microscopy-based image processing method. This PRS method does not require a priori knowledge of sample orientation nor composition and appears insensitive to changes in protein composition among different tissues. The Amplitude Alignment Metric introduced here could enable convenient and adaptable evaluation of protein alignment in soft tissues of varying protein and cell composition. STATEMENT OF SIGNIFICANCE: Polarized Raman spectroscopy (PRS) has been used to characterize the of organization of soft tissues. However, most of the reported applications of PRS have been on collagen-rich tissues and reliant on intensities of collagen-related vibrations. This work describes a PRS method via a multivariate analysis to characterize alignment in soft tissues composed of varying proteins. Of note, the highly aligned muscle layer of mouse skin was used to train a master function then applied to other soft tissue samples, and the degree of anisotropy in the PRS response was evaluated to obtain the level of alignment in tissues. We have demonstrated that this method supports convenient and adaptable evaluation of protein alignment in soft tissues of varying protein and cell composition.
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Affiliation(s)
- Hui Zhou
- Department of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, Florida, USA
| | - Janny Piñeiro Llanes
- J. Crayton Pruitt Family Department of Biomedical Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, Florida, USA
| | - Malisa Sarntinoranont
- Department of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, Florida, USA
| | - Ghatu Subhash
- Department of Mechanical and Aerospace Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, Florida, USA
| | - Chelsey S Simmons
- J. Crayton Pruitt Family Department of Biomedical Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, Florida, USA.
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Lin S, Li J, Shao J, Zhang J, He X, Huang D, Dong L, Lin J, Weng W, Cheng K. Anisotropic magneto-mechanical stimulation on collagen coatings to accelerate osteogenesis. Colloids Surf B Biointerfaces 2021; 210:112227. [PMID: 34838419 DOI: 10.1016/j.colsurfb.2021.112227] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Revised: 11/08/2021] [Accepted: 11/14/2021] [Indexed: 01/08/2023]
Abstract
Mechanical stimulation has been considered to be critical to cellular response and tissue regeneration. However, harnessing the direction of mechanical stimulation during osteogenesis still remains a challenge. In this study, we designed a series of novel magnetized collagen coatings (MCCs) (randomly or parallel-oriented collagen fibers) to exert the anisotropic mechanical stimulation using oriented magnetic actuation during osteogenesis. Strikingly, we found the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) were significantly up-regulated when the direction of magnetic actuation was parallel to the randomly-oriented collagen coating surface, in contrast to the down-regulated capacity under the perpendicular magnetic actuation. Moreover, further exerting a parallel mechanical stimulation along the parallel-oriented collagen coating, which cells have been oriented by the oriented collagens, were not only able to up-regulate the osteogenic differentiation of BMSCs but also promote the new bone formation during osteogenesis in vivo. We also demonstrated the anisotropic magneto-mechanical stimulation for the osteogenic differences might be attributed to the stretching or bending tensile status of collagen fibers controlled by the direction of magnetic actuation, driving the α5β1-dependent integrin signaling cascade. This study therefore got insight of understanding the directional mechanical stimulation on osteogenesis, and also paved a way for sustaining regulation of the biomaterials-host interface.
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Affiliation(s)
- Suya Lin
- School of Materials Science and Engineering, State Key Laboratory of Silicon Materials, Center of Rehabilitation Biomedical Materials, Cyrus Tang Center for Sensor Materials and Applications, Zhejiang University, Hangzhou 310027, China
| | - Juan Li
- The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Jiaqi Shao
- The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Jiamin Zhang
- School of Materials Science and Engineering, State Key Laboratory of Silicon Materials, Center of Rehabilitation Biomedical Materials, Cyrus Tang Center for Sensor Materials and Applications, Zhejiang University, Hangzhou 310027, China
| | - Xuzhao He
- School of Materials Science and Engineering, State Key Laboratory of Silicon Materials, Center of Rehabilitation Biomedical Materials, Cyrus Tang Center for Sensor Materials and Applications, Zhejiang University, Hangzhou 310027, China
| | - Donghua Huang
- Department of Orthopaedic Surgery, the Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China
| | - Lingqing Dong
- The Affiliated Stomatologic Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Jun Lin
- The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
| | - Wenjian Weng
- School of Materials Science and Engineering, State Key Laboratory of Silicon Materials, Center of Rehabilitation Biomedical Materials, Cyrus Tang Center for Sensor Materials and Applications, Zhejiang University, Hangzhou 310027, China
| | - Kui Cheng
- School of Materials Science and Engineering, State Key Laboratory of Silicon Materials, Center of Rehabilitation Biomedical Materials, Cyrus Tang Center for Sensor Materials and Applications, Zhejiang University, Hangzhou 310027, China; Department of Rehabilitation Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
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El Khatib M, Russo V, Prencipe G, Mauro A, Wyrwa R, Grimm G, Di Mattia M, Berardinelli P, Schnabelrauch M, Barboni B. Amniotic Epithelial Stem Cells Counteract Acidic Degradation By-Products of Electrospun PLGA Scaffold by Improving Their Immunomodulatory Profile In Vitro. Cells 2021; 10:cells10113221. [PMID: 34831443 PMCID: PMC8623927 DOI: 10.3390/cells10113221] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 11/12/2021] [Accepted: 11/16/2021] [Indexed: 12/25/2022] Open
Abstract
Electrospun poly(lactic-co-glycolic acid) (PLGA) scaffolds with highly aligned fibers (ha-PLGA) represent promising materials in the field of tendon tissue engineering (TE) due to their characteristics in mimicking fibrous extracellular matrix (ECM) of tendon native tissue. Among these properties, scaffold biodegradability must be controlled allowing its replacement by a neo-formed native tendon tissue in a controlled manner. In this study, ha-PLGA were subjected to hydrolytic degradation up to 20 weeks, under di-H2O and PBS conditions according to ISO 10993-13:2010. These were then characterized for their physical, morphological, and mechanical features. In vitro cytotoxicity tests were conducted on ovine amniotic epithelial stem cells (oAECs), up to 7 days, to assess the effect of non-buffered and buffered PLGA by-products at different concentrations on cell viability and their stimuli on oAECs’ immunomodulatory properties. The ha-PLGA scaffolds degraded slowly as evidenced by a slight decrease in mass loss (14%) and average molecular weight (35%), with estimated degradation half-time of about 40 weeks under di-H2O. The ultrastructure morphology of the scaffolds showed no significant fiber degradation even after 20 weeks, but alteration of fiber alignment was already evident at week 1. Moreover, mechanical properties decreased throughout the degradation times under wet as well as dry PBS conditions. The influence of acid degradation media on oAECs was dose-dependent, with a considerable effect at 7 days’ culture point. This effect was notably reduced by using buffered media. To a certain level, cells were able to compensate the generated inflammation-like microenvironment by upregulating IL-10 gene expression and favoring an anti-inflammatory rather than pro-inflammatory response. These in vitro results are essential to better understand the degradation behavior of ha-PLGA in vivo and the effect of their degradation by-products on affecting cell performance. Indeed, buffering the degradation milieu could represent a promising strategy to balance scaffold degradation. These findings give good hope with reference to the in vivo condition characterized by physiological buffering systems.
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Affiliation(s)
- Mohammad El Khatib
- Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy; (M.E.K.); (V.R.); (A.M.); (M.D.M.); (P.B.); (B.B.)
| | - Valentina Russo
- Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy; (M.E.K.); (V.R.); (A.M.); (M.D.M.); (P.B.); (B.B.)
| | - Giuseppe Prencipe
- Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy; (M.E.K.); (V.R.); (A.M.); (M.D.M.); (P.B.); (B.B.)
- Correspondence:
| | - Annunziata Mauro
- Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy; (M.E.K.); (V.R.); (A.M.); (M.D.M.); (P.B.); (B.B.)
| | - Ralf Wyrwa
- Department of Biomaterials, INNOVENT e.V., 07745 Jena, Germany; (R.W.); (G.G.); (M.S.)
| | - Gabriele Grimm
- Department of Biomaterials, INNOVENT e.V., 07745 Jena, Germany; (R.W.); (G.G.); (M.S.)
| | - Miriam Di Mattia
- Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy; (M.E.K.); (V.R.); (A.M.); (M.D.M.); (P.B.); (B.B.)
| | - Paolo Berardinelli
- Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy; (M.E.K.); (V.R.); (A.M.); (M.D.M.); (P.B.); (B.B.)
| | | | - Barbara Barboni
- Unit of Basic and Applied Biosciences, Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy; (M.E.K.); (V.R.); (A.M.); (M.D.M.); (P.B.); (B.B.)
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Garcia Garcia A, Perot JB, Beldjilali-Labro M, Dermigny Q, Naudot M, Le Ricousse S, Legallais C, Bedoui F. Monitoring mechanical stimulation for optimal tendon tissue engineering: A mechanical and biological multiscale study. J Biomed Mater Res A 2021; 109:1881-1892. [PMID: 33871170 DOI: 10.1002/jbm.a.37180] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 03/18/2021] [Accepted: 03/24/2021] [Indexed: 12/13/2022]
Abstract
To understand the effect of mechanical stimulation on cell response, bone marrow stromal cells were cultured on electrospun scaffolds under two distinct mechanical conditions (static and dynamic). Comparison between initial and final mechanical and biological properties of the cell-constructs were conducted over 14 days for both culturing conditions. As a result, mechanically stimulated constructs, in contrast to their static counterparts, showed evident mechanical-induced cell orientation, an effective aligned collagen and tenomodulin extracellular matrix. This orientation provides clues on the importance of mechanical stimulation to induce a tendon-like differentiation. In addition, cell and collagen orientation lead to enhanced storage modulus observed under dynamic stimulation. Altogether mechanical stimulation lead to (a) cell and matrix orientation through the sense of the stretch and (b) a dominant elastic response in the cell-constructs with a minor contribution of the viscosity in the global mechanical behavior. Such a correlation could help in further studies to better understand the effect of mechanical stimulation in tissue engineering.
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Affiliation(s)
- Alejandro Garcia Garcia
- CNRS, UMR 7338 Laboratory of Biomechanics and Bioengineering, Sorbonne Universités, Université de Technologie de Compiègne, Compiegne, France
| | - Jean-Baptiste Perot
- CNRS, UMR 7338 Laboratory of Biomechanics and Bioengineering, Sorbonne Universités, Université de Technologie de Compiègne, Compiegne, France
| | - Megane Beldjilali-Labro
- CNRS, UMR 7338 Laboratory of Biomechanics and Bioengineering, Sorbonne Universités, Université de Technologie de Compiègne, Compiegne, France
| | - Quentin Dermigny
- CNRS, UMR 7338 Laboratory of Biomechanics and Bioengineering, Sorbonne Universités, Université de Technologie de Compiègne, Compiegne, France
| | - Marie Naudot
- EA4666-LNPC-Immunologie Therapie Cellulaire Hématologie Cancers, CURS, Hopital Sud Avenue René Laennec, Salouel, France
| | - Sophie Le Ricousse
- EA4666-LNPC-Immunologie Therapie Cellulaire Hématologie Cancers, CURS, Hopital Sud Avenue René Laennec, Salouel, France
| | - Cecile Legallais
- CNRS, UMR 7338 Laboratory of Biomechanics and Bioengineering, Sorbonne Universités, Université de Technologie de Compiègne, Compiegne, France
| | - Fahmi Bedoui
- FRE CNRS 2012 Roberval Laboratory for Mechanics, Sorbonne Universités, Université de Technologie de Compiègne, Compiègne, France
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3D Printing of dynamic tissue scaffold by combining self-healing hydrogel and self-healing ferrogel. Colloids Surf B Biointerfaces 2021; 208:112108. [PMID: 34543778 DOI: 10.1016/j.colsurfb.2021.112108] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 08/31/2021] [Accepted: 09/06/2021] [Indexed: 11/24/2022]
Abstract
Hydrogels have been widely utilized in tissue engineering applications as functional and biological synthetic extracellular matrices (ECMs) can be created with gels. However, typical hydrogels cannot be exploited in 3D printing, especially in extrusion printing, unless post-cross-linking after printing is provided. Additionally, dynamic tissue scaffolds that can mimic ECM environments in the body have been demonstrated to be useful in tissue engineering. Here, we hypothesized that a 3D-printed dynamic tissue scaffold could be fabricated by combining self-healing hydrogel and self-healing ferrogel without post-cross-linking, which could be useful for the regulation of cell phenotype under magnetic stimulation. Hydrogels were formed from oxidized sodium hyaluronate and glycol chitosan, and adipic acid dihydrazide was additionally utilized for self-healing behavior of the gel. Superparamagnetic iron oxide nanoparticles (SPIONs) were also used to prepare a magnetically responsive hydrogel system (i.e., ferrogel). Physicochemical properties, cytotoxicity, and printability of the self-healing hydrogel/ferrogel system fabricated by a 3D printing process, were investigated. Dimensional changes in a tissue scaffold were achieved by the application of a magnetic field. Interestingly, chondrogenic differentiation of ATDC5 cells cultured within the dynamic tissue scaffold was enhanced by applying a magnetic field in vitro. This approach may be useful for fabricating dynamic tissue scaffolds by a 3D printing method for tissue engineering applications.
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Hou J, Yang R, Vuong I, Li F, Kong J, Mao HQ. Biomaterials strategies to balance inflammation and tenogenesis for tendon repair. Acta Biomater 2021; 130:1-16. [PMID: 34082095 DOI: 10.1016/j.actbio.2021.05.043] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Revised: 05/15/2021] [Accepted: 05/24/2021] [Indexed: 12/17/2022]
Abstract
Adult tendon tissue demonstrates a limited regenerative capacity, and the natural repair process leaves fibrotic scar tissue with inferior mechanical properties. Surgical treatment is insufficient to provide the mechanical, structural, and biochemical environment necessary to restore functional tissue. While numerous strategies including biodegradable scaffolds, bioactive factor delivery, and cell-based therapies have been investigated, most studies have focused exclusively on either suppressing inflammation or promoting tenogenesis, which includes tenocyte proliferation, ECM production, and tissue formation. New biomaterials-based approaches represent an opportunity to more effectively balance the two processes and improve regenerative outcomes from tendon injuries. Biomaterials applications that have been explored for tendon regeneration include formation of biodegradable scaffolds presenting topographical, mechanical, and/or immunomodulatory cues conducive to tendon repair; delivery of immunomodulatory or tenogenic biomolecules; and delivery of therapeutic cells such as tenocytes and stem cells. In this review, we provide the biological context for the challenges in tendon repair, discuss biomaterials approaches to modulate the immune and regenerative environment during the healing process, and consider the future development of comprehensive biomaterials-based strategies that can better restore the function of injured tendon. STATEMENT OF SIGNIFICANCE: Current strategies for tendon repair focus on suppressing inflammation or enhancing tenogenesis. Evidence indicates that regulated inflammation is beneficial to tendon healing and that excessive tissue remodeling can cause fibrosis. Thus, it is necessary to adopt an approach that balances the benefits of regulated inflammation and tenogenesis. By reviewing potential treatments involving biodegradable scaffolds, biological cues, and therapeutic cells, we contrast how each strategy promotes or suppresses specific repair steps to improve the healing outcome, and highlight the advantages of a comprehensive approach that facilitates the clearance of necrotic tissue and recruitment of cells during the inflammatory stage, followed by ECM synthesis and organization in the proliferative and remodeling stages with the goal of restoring function to the tendon.
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Zhang S, Xiao X, Kong J, Lu K, Dou SX, Wang PY, Ma L, Liu Y, Li G, Li W, Zhang H. DNA polymerase Gp90 activities and regulations on strand displacement DNA synthesis revealed at single-molecule level. FASEB J 2021; 35:e21607. [PMID: 33908664 DOI: 10.1096/fj.202100033rr] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Revised: 03/18/2021] [Accepted: 04/05/2021] [Indexed: 11/11/2022]
Abstract
Strand displacement DNA synthesis (SDDS) is an essential step in DNA replication. With magnetic tweezers, we investigated SDDS kinetics of wild-type gp90 and its exonuclease-deficient polymerase gp90 exo- at single-molecule level. A novel binding state of gp90 to the fork flap was confirmed prior to SDDS, suggesting an intermediate in the initiation of SDDS. The rate and processivity of SDDS by gp90 exo- or wt-gp90 are increased with force and dNTP concentration. The rate and processivity of exonuclease by wt-gp90 are decreased with force. High GC content decreases SDDS and exonuclease processivity but increases exonuclease rate for wt-gp90. The high force and dNTP concentration and low GC content facilitate the successive SDDS but retard the successive exonuclease for wt-gp90. Furthermore, increasing GC content accelerates the transition from SDDS or exonuclease to exonuclease. This work reveals the kinetics of SDDS in detail and offers a broader cognition on the regulation of various factors on SDDS at single-polymerase level.
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Affiliation(s)
- Shuming Zhang
- Key Laboratory of Environment and Female Reproductive Health, West China School of Public Health & West China Fourth Hospital, Sichuan University, Chengdu, China.,National Laboratory for Condensed Matter Physics and Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, China
| | - Xue Xiao
- National Laboratory for Condensed Matter Physics and Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, China.,University of Chinese Academy of Sciences, Beijing, China
| | - Jingwei Kong
- National Laboratory for Condensed Matter Physics and Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, China.,University of Chinese Academy of Sciences, Beijing, China
| | - Ke Lu
- National Laboratory for Condensed Matter Physics and Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, China.,University of Chinese Academy of Sciences, Beijing, China
| | - Shuo-Xing Dou
- National Laboratory for Condensed Matter Physics and Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, China.,University of Chinese Academy of Sciences, Beijing, China
| | - Peng-Ye Wang
- National Laboratory for Condensed Matter Physics and Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, China.,University of Chinese Academy of Sciences, Beijing, China.,Songshan Lake Materials Laboratory, Dongguan, China
| | - Lu Ma
- National Laboratory for Condensed Matter Physics and Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, China
| | - Yuru Liu
- National Laboratory for Condensed Matter Physics and Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, China
| | - Guohong Li
- National Laboratory of Biomacromolecules, CAS Centre for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
| | - Wei Li
- National Laboratory for Condensed Matter Physics and Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, China.,Songshan Lake Materials Laboratory, Dongguan, China
| | - Huidong Zhang
- Key Laboratory of Environment and Female Reproductive Health, West China School of Public Health & West China Fourth Hospital, Sichuan University, Chengdu, China.,Research Center for Environment and Female Reproductive Health, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
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45
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Mosher CZ, Brudnicki PAP, Gong Z, Childs HR, Lee SW, Antrobus RM, Fang EC, Schiros TN, Lu HH. Green electrospinning for biomaterials and biofabrication. Biofabrication 2021; 13. [PMID: 34102612 DOI: 10.1088/1758-5090/ac0964] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Accepted: 06/08/2021] [Indexed: 11/12/2022]
Abstract
Green manufacturing has emerged across industries, propelled by a growing awareness of the negative environmental and health impacts associated with traditional practices. In the biomaterials industry, electrospinning is a ubiquitous fabrication method for producing nano- to micro-scale fibrous meshes that resemble native tissues, but this process traditionally utilizes solvents that are environmentally hazardous and pose a significant barrier to industrial scale-up and clinical translation. Applying sustainability principles to biomaterial production, we have developed a 'green electrospinning' process by systematically testing biologically benign solvents (U.S. Food and Drug Administration Q3C Class 3), and have identified acetic acid as a green solvent that exhibits low ecological impact (global warming potential (GWP) = 1.40 CO2eq. kg/L) and supports a stable electrospinning jet under routine fabrication conditions. By tuning electrospinning parameters, such as needle-plate distance and flow rate, we updated the fabrication of widely utilized biomedical polymers (e.g. poly-α-hydroxyesters, collagen), polymer blends, polymer-ceramic composites, and growth factor delivery systems. Resulting 'green' fibers and composites are comparable to traditional meshes in terms of composition, chemistry, architecture, mechanical properties, and biocompatibility. Interestingly, material properties of green synthetic fibers are more biomimetic than those of traditionally electrospun fibers, doubling in ductility (91.86 ± 35.65 vs. 45 ± 15.07%,n= 10,p< 0.05) without compromising yield strength (1.32 ± 0.26 vs. 1.38 ± 0.32 MPa) or ultimate tensile strength (2.49 ± 0.55 vs. 2.36 ± 0.45 MPa). Most importantly, green electrospinning proves advantageous for biofabrication, rendering a greater protection of growth factors during fiber formation (72.30 ± 1.94 vs. 62.87 ± 2.49% alpha helical content,n= 3,p< 0.05) and recapitulating native ECM mechanics in the fabrication of biopolymer-based meshes (16.57 ± 3.92% ductility, 33.38 ± 30.26 MPa elastic modulus, 1.30 ± 0.19 MPa yield strength, and 2.13 ± 0.36 MPa ultimate tensile strength,n= 10). The eco-conscious approach demonstrated here represents a paradigm shift in biofabrication, and will accelerate the translation of scalable biomaterials and biomimetic scaffolds for tissue engineering and regenerative medicine.
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Affiliation(s)
- Christopher Z Mosher
- Biomaterials and Interface Tissue Engineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY 10027, United States of America
| | - Philip A P Brudnicki
- Biomaterials and Interface Tissue Engineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY 10027, United States of America
| | - Zhengxiang Gong
- Biomaterials and Interface Tissue Engineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY 10027, United States of America
| | - Hannah R Childs
- Biomaterials and Interface Tissue Engineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY 10027, United States of America
| | - Sang Won Lee
- Biomaterials and Interface Tissue Engineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY 10027, United States of America
| | - Romare M Antrobus
- Biomaterials and Interface Tissue Engineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY 10027, United States of America
| | - Elisa C Fang
- Biomaterials and Interface Tissue Engineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY 10027, United States of America
| | - Theanne N Schiros
- Materials Research Science and Engineering Center, Columbia University, New York, NY 10027, United States of America.,Science and Mathematics Department, Fashion Institute of Technology, New York, NY 10001, United States of America
| | - Helen H Lu
- Biomaterials and Interface Tissue Engineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, NY 10027, United States of America.,Materials Research Science and Engineering Center, Columbia University, New York, NY 10027, United States of America
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46
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Poddar S, Agarwal PS, Sahi AK, Varshney N, Vajanthri KY, Mahto SK. Fabrication and characterization of electrospun psyllium husk‐based nanofibers for tissue regeneration. J Appl Polym Sci 2021. [DOI: 10.1002/app.50569] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Suruchi Poddar
- Tissue Engineering and Biomicrofluidics Laboratory, School of Biomedical Engineering Indian Institute of Technology (Banaras Hindu University) Varanasi India
| | - Piyush Sunil Agarwal
- Tissue Engineering and Biomicrofluidics Laboratory, School of Biomedical Engineering Indian Institute of Technology (Banaras Hindu University) Varanasi India
- Department of Materials Engineering Indian Institute of Science Bangalore India
| | - Ajay Kumar Sahi
- Tissue Engineering and Biomicrofluidics Laboratory, School of Biomedical Engineering Indian Institute of Technology (Banaras Hindu University) Varanasi India
| | - Neelima Varshney
- Tissue Engineering and Biomicrofluidics Laboratory, School of Biomedical Engineering Indian Institute of Technology (Banaras Hindu University) Varanasi India
| | - Kiran Yellappa Vajanthri
- Tissue Engineering and Biomicrofluidics Laboratory, School of Biomedical Engineering Indian Institute of Technology (Banaras Hindu University) Varanasi India
| | - Sanjeev Kumar Mahto
- Tissue Engineering and Biomicrofluidics Laboratory, School of Biomedical Engineering Indian Institute of Technology (Banaras Hindu University) Varanasi India
- Centre for Advanced Biomaterials and Tissue Engineering Indian Institute of Technology (Banaras Hindu University) Varanasi India
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47
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Theodossiou SK, Pancheri NM, Martes AC, Bozeman AL, Brumley MR, Raveling AR, Courtright JM, Schiele NR. Neonatal Spinal Cord Transection Decreases Hindlimb Weight-Bearing and Affects Formation of Achilles and Tail Tendons. J Biomech Eng 2021; 143:061012. [PMID: 33537729 PMCID: PMC8114905 DOI: 10.1115/1.4050031] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 01/06/2021] [Indexed: 01/08/2023]
Abstract
Mechanical loading may be required for proper tendon formation. However, it is not well understood how tendon formation is impacted by the development of weight-bearing locomotor activity in the neonate. This study assessed tendon mechanical properties, and concomitant changes in weight-bearing locomotion, in neonatal rats subjected to a low thoracic spinal cord transection or a sham surgery at postnatal day (P)1. On P10, spontaneous locomotion was evaluated in spinal cord transected and sham controls to determine impacts on weight-bearing hindlimb movement. The mechanical properties of P10 Achilles tendons (ATs), as representative energy-storing, weight-bearing tendons, and tail tendons (TTs), as representative positional, non-weight-bearing tendons were evaluated. Non- and partial weight-bearing hindlimb activity decreased in spinal cord transected rats compared to sham controls. No spinal cord transected rats showed full weight-bearing locomotion. ATs from spinal cord transected rats had increased elastic modulus, while cross-sectional area trended lower compared to sham rats. TTs from spinal cord transected rats had higher stiffness and cross-sectional area. Collagen structure of ATs and TTs did not appear impacted by surgery condition, and no significant differences were detected in the collagen crimp pattern. Our findings suggest that mechanical loading from weight-bearing locomotor activity during development regulates neonatal AT lateral expansion and maintains tendon compliance, and that TTs may be differentially regulated. The onset and gradual increase of weight-bearing movement in the neonate may provide the mechanical loading needed to direct functional postnatal tendon formation.
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Affiliation(s)
- Sophia K. Theodossiou
- Biological Engineering, University of Idaho, 875 Perimeter Drive, MS 0904, Moscow, ID 83844
| | - Nicholas M. Pancheri
- Biological Engineering, University of Idaho, 875 Perimeter Drive, MS 0904, Moscow, ID 83844
| | - Alleyna C. Martes
- Psychology, Idaho State University, 921 South 8th Avenue Stop 8112, Pocatello, ID 83209
| | - Aimee L. Bozeman
- Psychology, Idaho State University, 921 South 8th Avenue Stop 8112, Pocatello, ID 83209
| | - Michele R. Brumley
- Psychology, Idaho State University, 921 South 8th Avenue Stop 8087, Pocatello, ID 83209
| | - Abigail R. Raveling
- Biological Engineering, University of Idaho, 875 Perimeter Drive, MS 0904, Moscow, ID 83844
| | - Jeffrey M. Courtright
- Biological Engineering, University of Idaho, 875 Perimeter Drive, MS 0904, Moscow, ID 83844
| | - Nathan R. Schiele
- Biological Engineering, University of Idaho, 875 Perimeter Drive, MS 0904, Moscow, ID 83844
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48
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Ahmed A, Joshi IM, Mansouri M, Ahamed NNN, Hsu MC, Gaborski TR, Abhyankar VV. Engineering fiber anisotropy within natural collagen hydrogels. Am J Physiol Cell Physiol 2021; 320:C1112-C1124. [PMID: 33852366 PMCID: PMC8285641 DOI: 10.1152/ajpcell.00036.2021] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 04/06/2021] [Accepted: 04/06/2021] [Indexed: 12/14/2022]
Abstract
It is well known that biophysical properties of the extracellular matrix (ECM), including stiffness, porosity, composition, and fiber alignment (anisotropy), play a crucial role in controlling cell behavior in vivo. Type I collagen (collagen I) is a ubiquitous structural component in the ECM and has become a popular hydrogel material that can be tuned to replicate the mechanical properties found in vivo. In this review article, we describe popular methods to create 2-D and 3-D collagen I hydrogels with anisotropic fiber architectures. We focus on methods that can be readily translated from engineering and materials science laboratories to the life-science community with the overall goal of helping to increase the physiological relevance of cell culture assays.
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Affiliation(s)
- Adeel Ahmed
- Department of Microsystems Engineering, Rochester Institute of Technology, Rochester, New York
| | - Indranil M Joshi
- Department of Biomedical Engineering, Rochester Institute of Technology, Rochester, New York
| | - Mehran Mansouri
- Department of Microsystems Engineering, Rochester Institute of Technology, Rochester, New York
| | - Nuzhet N N Ahamed
- Department of Microsystems Engineering, Rochester Institute of Technology, Rochester, New York
| | - Meng-Chun Hsu
- Department of Microsystems Engineering, Rochester Institute of Technology, Rochester, New York
| | - Thomas R Gaborski
- Department of Microsystems Engineering, Rochester Institute of Technology, Rochester, New York
- Department of Biomedical Engineering, Rochester Institute of Technology, Rochester, New York
| | - Vinay V Abhyankar
- Department of Microsystems Engineering, Rochester Institute of Technology, Rochester, New York
- Department of Biomedical Engineering, Rochester Institute of Technology, Rochester, New York
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49
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Klatte-Schulz F, Bormann N, Voss I, Melzer J, Schmock A, Bucher CH, Thiele K, Moroder P, Haffner-Luntzer M, Ignatius A, Duda GN, Wildemann B. Bursa-Derived Cells Show a Distinct Mechano-Response to Physiological and Pathological Loading in vitro. Front Cell Dev Biol 2021; 9:657166. [PMID: 34136480 PMCID: PMC8201779 DOI: 10.3389/fcell.2021.657166] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Accepted: 04/09/2021] [Indexed: 11/13/2022] Open
Abstract
The mechano-response of highly loaded tissues such as bones or tendons is well investigated, but knowledge regarding the mechano-responsiveness of adjacent tissues such as the subacromial bursa is missing. For a better understanding of the physiological role of the bursa as a friction-reducing structure in the joint, the study aimed to analyze whether and how bursa-derived cells respond to physiological and pathological mechanical loading. This might help to overcome some of the controversies in the field regarding the role of the bursa in the development and healing of shoulder pathologies. Cells of six donors seeded on collagen-coated silicon dishes were stimulated over 3 days for 1 or 4 h with 1, 5, or 10% strain. Orientation of the actin cytoskeleton, YAP nuclear translocation, and activation of non-muscle myosin II (NMM-II) were evaluated for 4 h stimulations to get a deeper insight into mechano-transduction processes. To investigate the potential of bursa-derived cells to adapt their matrix formation and remodeling according to mechanical loading, outcome measures included cell viability, gene expression of extracellular matrix and remodeling markers, and protein secretions. The orientation angle of the actin cytoskeleton increased toward a more perpendicular direction with increased loading and lowest variations for the 5% loading group. With 10% tension load, cells were visibly stressed, indicated by loss in actin density and slightly reduced cell viability. A significantly increased YAP nuclear translocation occurred for the 1% loading group with a similar trend for the 5% group. NMM-II activation was weak for all stimulation conditions. On the gene expression level, only the expression of TIMP2 was down-regulated in the 1 h group compared to control. On the protein level, collagen type I and MMP2 increased with higher/longer straining, respectively, whereas TIMP1 secretion was reduced, resulting in an MMP/TIMP imbalance. In conclusion, this study documents for the first time a clear mechano-responsiveness in bursa-derived cells with activation of mechano-transduction pathways and thus hint to a physiological function of mechanical loading in bursa-derived cells. This study represents the basis for further investigations, which might lead to improved treatment options of subacromial bursa-related pathologies in the future.
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Affiliation(s)
- Franka Klatte-Schulz
- Julius Wolff Institute, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.,BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Nicole Bormann
- Julius Wolff Institute, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.,BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Isabel Voss
- Julius Wolff Institute, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Josephine Melzer
- Julius Wolff Institute, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Aysha Schmock
- Julius Wolff Institute, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.,BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Christian H Bucher
- Julius Wolff Institute, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.,BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Kathi Thiele
- Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Philipp Moroder
- Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | | | - Anita Ignatius
- Institute of Orthopaedic Research and Biomechanics, Ulm University, Ulm, Germany
| | - Georg N Duda
- Julius Wolff Institute, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.,BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Britt Wildemann
- Julius Wolff Institute, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.,Experimental Trauma Surgery, Department of Trauma-, Hand- and Reconstructive Surgery, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany
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50
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Jiang S, Wang M, He J. A review of biomimetic scaffolds for bone regeneration: Toward a cell-free strategy. Bioeng Transl Med 2021; 6:e10206. [PMID: 34027093 PMCID: PMC8126827 DOI: 10.1002/btm2.10206] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Revised: 11/05/2020] [Accepted: 11/12/2020] [Indexed: 12/20/2022] Open
Abstract
In clinical terms, bone grafting currently involves the application of autogenous, allogeneic, or xenogeneic bone grafts, as well as natural or artificially synthesized materials, such as polymers, bioceramics, and other composites. Many of these are associated with limitations. The ideal scaffold for bone tissue engineering should provide mechanical support while promoting osteogenesis, osteoconduction, and even osteoinduction. There are various structural complications and engineering difficulties to be considered. Here, we describe the biomimetic possibilities of the modification of natural or synthetic materials through physical and chemical design to facilitate bone tissue repair. This review summarizes recent progresses in the strategies for constructing biomimetic scaffolds, including ion-functionalized scaffolds, decellularized extracellular matrix scaffolds, and micro- and nano-scale biomimetic scaffold structures, as well as reactive scaffolds induced by physical factors, and other acellular scaffolds. The fabrication techniques for these scaffolds, along with current strategies in clinical bone repair, are described. The developments in each category are discussed in terms of the connection between the scaffold materials and tissue repair, as well as the interactions with endogenous cells. As the advances in bone tissue engineering move toward application in the clinical setting, the demonstration of the therapeutic efficacy of these novel scaffold designs is critical.
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Affiliation(s)
- Sijing Jiang
- Department of Plastic SurgeryFirst Affiliated Hospital of Anhui Medical University, Anhui Medical UniversityHefeiChina
| | - Mohan Wang
- Stomatologic Hospital & College, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui ProvinceHefeiChina
| | - Jiacai He
- Stomatologic Hospital & College, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui ProvinceHefeiChina
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