MSC‐Laden Composite Hydrogels for Inflammation and Angiogenic Regulation for Skin Flap Repair

Abstract Pressure‐driven, spreadable, deferoxamine (DFO)‐laden hydrogels are developed toward treatment for improved skin flap tissue repair. Further, mesenchymal stem cells (MSCs) are incorporated into silk nanofiber systems and then added to silk hydrogels to optimize angiogenesis and moderate inflammatory reactions in skin flap tissues for repair. The combined (composite) systems result in improved tissue outcomes. For example, the DFO release from the hydrogels is maintained while the system moderated negative influences of DFO on cells at the skin flap site with improved vasculization and for control of immune reactions. Both in vitro and in vivo results reveal improved outcomes with these composite hydrogel systems when MSCs are included. The synergistic action of DFO‐laden silk nanofibers combined with MSC‐laden microgels results in improved functional recovery of skin flaps in vivo when compared to control systems. Considering the ease of use of this system toward clinical applications, these new hydrogels are candidates for skin flap regeneration in surgical settings.