Self-assembled polyoxometalate–phenolic nanodrugs integrated with dissolving microneedles for hypertrophic scar combination therapy

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.