PAM@GO Composite Scaffolds Enhance the Yield of iMEC Exosomes for Accelerated Burn Repair.

Abstract

Severe burns trigger widespread tissue necrosis and a persistent inflammatory cascade, demanding the development of advanced biomaterials capable of actively promoting cutaneous regeneration. In this study, we present a multifunctional hydrogel system integrating a polyacrylamide-graphene oxide (PAM@GO) matrix, capable of promoting induced mammary epithelial-like cells (iMECs) to achieve the high-yield production of exosomes (PAM@GO-EXOs-iMECs), and enhance the biological functions. Mechanistically, iMECs exosome biogenesis can be enhanced by both activating RAB27A/B-mediated vesicular trafficking and upregulating the critical MITF-NSMASE2 signaling axis. Furthermore, in vitro assays demonstrated that PAM@GO-EXOs-iMECs significantly stimulated keratinocyte proliferation and migration, alongside robust endothelial tube formation compared to 2D-EXOs-iMECs. The PAM@GO-EXOs-iMECs were subsequently encapsulated within a methoxy polyethylene glycol (MPEG) hydrogel to form a sustained-release bioactive dressing (PAM@GO-EXOs-MPEG). In murine burn models, PAM@GO-EXOs-MPEG accelerated wound closure, improved collagen alignment, and fostered neovascularization compared to 2D-EXOs-iMECs. Meanwhile, proteomic profiling revealed profound enrichment of proteins linked to epidermal development, cytoskeletal reorganization, and inflammatory resolution following treatment with PAM@GO-EXOs-MPEG. Collectively, this work establishes an innovative PAM@GO scalable platform for significantly promoting exosome production and introduces a clinically translatable exosome-hydrogel hybrid with substantial regenerative potential for severe burn repair.