Physical and Soluble Cues Enhance Tendon Progenitor Cell Invasion into Injectable Synthetic Hydrogels

Robert N. Kent, Mohamed Said, Megan E. Busch, Ethan R. Poupard, Ariane Tsai, Jingyi Xia, Daniel L. Matera, William Y. Wang, Samuel J. DePalma, Harrison L. Hiraki, Megan L. Killian, Adam C. Abraham, Jae Won Shin, Alice H. Huang, Ariella Shikanov, Brendon M. Baker

Research output: Contribution to journalArticlepeer-review


Synthetic hydrogels represent an exciting avenue in the field of regenerative biomaterials given their injectability, orthogonally tunable mechanical properties, and potential for modular inclusion of cellular cues. Separately, recent advances in soluble factor release technology have facilitated control over the soluble milieu in cell microenvironments via tunable microparticles. A composite hydrogel incorporating both of these components can robustly mediate tendon healing following a single injection. Here, a synthetic hydrogel system with encapsulated electrospun fiber segments and a novel microgel-based soluble factor delivery system achieves precise control over topographical and soluble features of an engineered microenvironment, respectively. It is demonstrated that three-dimensional migration of tendon progenitor cells can be enhanced via combined mechanical, topographical, and microparticle-delivered soluble cues in both a tendon progenitor cell spheroid model and an ex vivo murine Achilles tendon model. These results indicate that fiber reinforced hydrogels can drive the recruitment of endogenous progenitor cells relevant to the regeneration of tendon and, likely, a broad range of connective tissues.

Original languageEnglish
Article number2207556
JournalAdvanced Functional Materials
Issue number48
StatePublished - 24 Nov 2022
Externally publishedYes


  • endogenous cell recruitment
  • fiber-reinforced synthetic hydrogels
  • injectable biomaterials
  • soluble factor release
  • tendon regeneration


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