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 (Mo154) and epigallocatechin gallate (EGCG), followed by chitosan encapsulation, to generate chitosan-encapsulated Mo154/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.
Du et al. (Sun,) studied this question.