Immunoregulatory properties of the human acellular amniotic membrane for diabetic wound healing

Repair of chronic diabetic wounds remains a major clinical challenge, and the immunoregulatory mechanisms of the human acellular amniotic membrane (HAAM) are not fully understood. Using a db/db type 2 diabetic mouse model with full-thickness dorsal wounds, this study evaluated the therapeutic effects of the HAAM compared with conventional gauze in wound healing. Compared with the control group, the HAAM group exhibited significantly accelerated wound closure and enhanced collagen deposition. Single-cell RNA sequencing revealed that the HAAM reshaped the immune microenvironment by promoting chemotactic, tissue-reparative macrophage phenotypes while reducing S100a9+ neutrophils linked to neutrophil extracellular traps. Intercellular communication analysis indicated enhanced macrophage-neutrophil interactions via Spp1-CD44 signaling. HAAM-treated wounds upregulated prodegenerative and angiogenic genes and exhibited balanced matrix remodeling. Overall, the findings indicated that the HAAM promoted diabetic wound healing by reducing excessive inflammation and activating regenerative pathways, highlighting its potential as a bioactive scaffold for next-generation immunomodulatory biomaterials.