Affiliation:
1. Department of Biomedical Engineering University of Michigan Ann Arbor MI 48109 USA
2. Department of Orthopedic Surgery University of Michigan Ann Arbor MI 48109 USA
3. Department of Orthopedic Surgery Columbia University New York NY 10027 USA
4. Department of Chemical Engineering University of Michigan Ann Arbor MI 48109 USA
Abstract
AbstractEffective tendon regeneration following injury is contingent on appropriate differentiation of recruited cells and deposition of mature, aligned, collagenous extracellular matrix that can withstand the extreme mechanical demands placed on the tissue. As such, myriad biomaterial approaches have been explored to provide biochemical and physical cues that encourage tenogenesis and template aligned matrix deposition in lieu of dysfunctional scar tissue formation. Fiber‐reinforced hydrogels present an ideal biomaterial system toward this end given their transdermal injectability, tunable stiffness over a range amenable to tenogenic differentiation of progenitors, and capacity for modular inclusion of biochemical cues. Here, tunable and modular, fiber‐reinforced, synthetic hydrogels are employed to elucidate salient microenvironmental determinants of tenogenesis and aligned collagen deposition by tendon progenitor cells. Transforming growth factor β3 drives a cell fate switch toward pro‐regenerative or pro‐fibrotic phenotypes, which can be biased toward the former by culture in softer microenvironments or inhibition of the RhoA/ROCK activity. Furthermore, studies demonstrate that topographical anisotropy in fiber‐reinforced hydrogels critically mediates the alignment of de novo collagen fibrils, reflecting native tendon architecture. These findings inform the design of cell‐free, injectable, synthetic hydrogels for tendon tissue regeneration and, likely, that of a range of load‐bearing connective tissues.
Funder
National Science Foundation
National Institute of Arthritis and Musculoskeletal and Skin Diseases
National Institute of Dental and Craniofacial Research
Cited by
2 articles.
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