Cell-homing and immunomodulatory composite hydrogels for effective wound healing with neovascularization

Wound healing in cases of excessive inflammation poses a significant challenge due to compromised neovascularization.Here,we propose a multi-functional composite hydrogel engineered to overcome such conditions through recruitment and activation of macrophages with adapted degradation of the hydrogel.The composite hydrogel(G-TSrP)is created by combining gelatin methacryloyl(GelMA)and nanoparticles(TSrP)composed of tannic acid(TA)and Sr^(2+).These nanoparticles are prepared using a one-step mineralization process assisted by metal-phenolic network formation.G-TSrP exhibits the ability to eliminate reactive oxygen species and direct polarization of macrophages toward M2 phenotype.It has been observed that the liberation of TA and Sr^(2+)from G-TSrP actively facilitate the recruitment and up-regulation of the expression of extracellular matrix remodeling genes of macrophages,and thereby,coordinate in vivo adapted degradation of the G-TSrP.Most significantly,G-TSrP accelerates angiogenesis despite the TA’s inhibitory properties,which are counteracted by the released Sr^(2+).Moreover,G-TSrP enhances wound closure under inflammation and promotes normal tissue formation with strong vessel growth.Genetic analysis confirms macrophage-mediated wound healing by the composite hydrogel.Collectively,these findings pave the way for the development of biomaterials that promote wound healing by creating regenerative environment.