Human placental matrix hydrogel: A biomaterial for modulating inflammation and promoting repair of refractory diabetic wounds

Diabetic wound healing is impaired due to persistent inflammation and dysfunctional angiogenesis, creating a clinical demand for ideal dressings capable of modulating the immune microenvironment. While the extracellular matrix (ECM) serves as an excellent biomaterial, most ECM sources are animal-derived, carrying risks of immunogenicity and disease transmission. Human placental tissue, rich in ECM and bioactive factors, represents an ideal human-derived biomaterial, though its direct application is limited by poor handling and shape adaptability. This study developed a biological gel—human placental matrix (hPM)—from decellularized and enzymatically digested human placenta, which exhibits injectability and good biocompatibility. In both cellular and animal experiments, hPM showed improved cell proliferation, migration, and angiogenesis compared to conventional rat tail collagen (Col I). Further investigations revealed that hPM significantly inhibits macrophage polarization toward the M1 pro-inflammatory phenotype and reduces the expression of inflammatory cytokines such as TNF-α, iNOS, and IL-1β, thereby improving the inflammatory microenvironment and accelerating wound healing in diabetic rats. This study not only provides a novel human-derived biomaterial for the treatment of refractory wounds such as those in diabetes but also proposes an innovative strategy for the medical repurposing of placental resources, by utilizing discarded clinical human placentas through a standardized, nuclease-assisted decellularization process to obtain an injectable extracellular matrix (ECM) hydrogel distinct from traditional dehydrated or membrane-based placenta products.