The clinical management of hypertrophic scars(HSs)remains challenging due to their complex etiology and heterogeneous morphology,underscoring the need for multitarget treatment strategies.In this study,we developed a ...The clinical management of hypertrophic scars(HSs)remains challenging due to their complex etiology and heterogeneous morphology,underscoring the need for multitarget treatment strategies.In this study,we developed a nanocomposite system constructed through the metal-phenolic network-mediated self-assembly of molybdenum polyoxometalate({Mo 154})and epigallocatechin gallate(EGCG),followed by chitosan encapsulation,to generate chitosan-encapsulated{Mo 154}/EGCG(CME)nanoparticles.These nanoparticles were integrated into dissolvable microneedles(CME@MN)to enable transdermal administration.Under near-infrared laser irradiation,CME exhibited a three-pronged therapeutic effect:suppression of collagen overproduction and excessive extracellular matrix(ECM)deposition in human keloid fibroblasts,regulation of proliferation and migration in human umbilical vein endothelial cells,and reprogramming of macrophages toward a proinflammatory M1 phenotype.In vivo,CME@MN patches preferentially accumulated within scar tissue,where they normalized ECM organization,improved collagen fiber rearrangement,and attenuated fibroblast activity through photothermal-enhanced mechanisms while maintaining an excellent safety profile.The CME@MN system represents a potentially transformative approach to HS management by offering a unified platform that simultaneously targets the fibrotic,angiogenic,and inflammatory components of scar pathogenesis.展开更多
基金the financial support from the Fujian Provincial Youth Top-Notch Talent Support Program,China.
文摘The clinical management of hypertrophic scars(HSs)remains challenging due to their complex etiology and heterogeneous morphology,underscoring the need for multitarget treatment strategies.In this study,we developed a nanocomposite system constructed through the metal-phenolic network-mediated self-assembly of molybdenum polyoxometalate({Mo 154})and epigallocatechin gallate(EGCG),followed by chitosan encapsulation,to generate chitosan-encapsulated{Mo 154}/EGCG(CME)nanoparticles.These nanoparticles were integrated into dissolvable microneedles(CME@MN)to enable transdermal administration.Under near-infrared laser irradiation,CME exhibited a three-pronged therapeutic effect:suppression of collagen overproduction and excessive extracellular matrix(ECM)deposition in human keloid fibroblasts,regulation of proliferation and migration in human umbilical vein endothelial cells,and reprogramming of macrophages toward a proinflammatory M1 phenotype.In vivo,CME@MN patches preferentially accumulated within scar tissue,where they normalized ECM organization,improved collagen fiber rearrangement,and attenuated fibroblast activity through photothermal-enhanced mechanisms while maintaining an excellent safety profile.The CME@MN system represents a potentially transformative approach to HS management by offering a unified platform that simultaneously targets the fibrotic,angiogenic,and inflammatory components of scar pathogenesis.
