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...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.展开更多
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(No.RS-2023-00207746,RS-2023-00207983)a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(grant number:HI19C075300).
文摘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.
