Human skin-derived micronized acellular dermal matrix modulates angiogenesis to enhance tissue reconstruction

Abstract

Tissue reconstruction is essential for restoring form and function in patients affected by trauma, surgical resection, or congenital abnormalities. Although implant-based techniques such as silicone implants and biological methods like autologous fat grafting are widely used, complications-including immune reactions, fibrosis, and necrosis-remain unresolved. Acellular dermal matrix (ADM), derived from decellularized human skin tissue, retains the extracellular matrix and growth factors while removing immunogenic components. Angiogenesis, the formation of new blood vessels, is critical for tissue reconstruction as it ensures nutrient delivery, supports tissue formation, and reduces implant-associated complications. This study investigated the angiogenic potential of micronized ADM (mADM), produced via supercritical carbon dioxide decellularization, both in vivo and in vitro, and explored its underlying molecular mechanisms. Human umbilical vein endothelial cells (HUVECs) and a murine model were used to evaluate the regulatory effects of mADM on angiogenesis through molecular and functional assays. mADM-treated HUVECs exhibited upregulation of angiogenesis-related genes and activation of the protein kinase B and extracellular signal-regulated kinase pathways, enhancing endothelial cell proliferation and migration. mADM also stimulated vascular endothelial growth factor receptor 2 signaling, promoting angiogenic activity. In vivo, mADM injection led to sustained material retention and induced neovascularization, as evidenced by CD31 immunostaining. These findings demonstrate that mADM supports angiogenesis through defined molecular pathways, offering a promising bioactive material for improving tissue reconstruction and addressing the limitations of conventional approaches.