Study of stiffness effects of poly(amidoamine)-poly(n-isopropyl acrylamide) hydrogel on wound healing

The mechanical miss-match between the host and an implanted foreign body is one of the primary causes for implantation failure. To enhance the efficacy in wound repair, we developed stiffness-tunable temperature-sensitive hydrogels composed of poly(amidoamine) (PAA)-based poly(n-isopropyl acrylamide) (PNIPAM). PNIPAM-PAA hydrogels with three different stiffness fabricated by varying the concentrations of poly(amidoamine) were chosen for morphology and rheology tests. The degradation rate and cell compatibility of gels were also characterized. The PAA-PNIPAM hydrogels were then tested in a wound healing model of mice with full-thickness skin loss. We found that the stiffness of hydrogels has an impact on the wound healing process mainly by regulating the cell activities in the proliferation phase. PNIPAM-PAA hydrogels with appropriate stiffness reduce scar formation and improve wound healing by promoting myofibroblast transformation, keratinocytes proliferation, extracellular matrix synthesis and remodeling. Moreover, the stiffness of hydrogels impact on the secretion of TGF-β1 and bFGF, which play an important role in skin wound healing. These results suggest that the therapeutic effects of hydrogels in skin wound healing can by regulated by hydrogels' stiffness.