Ultra-fine Micronized Human Acellular Dermal Matrix Promotes Diabetic Wound Healing in a Mouse Model

Diabetic wounds are characterized by chronic inflammation, impaired angiogenesis, and abnormal extracellular matrix (ECM) remodeling, which contribute to delayed wound healing and non-healing ulcers. Because ECM degradation and impaired matrix repair are central features of diabetic wound pathology, we evaluated an ultra-fine micronized human acellular dermal matrix (UFM-hADM; mean particle size approximately 70 μm) as an injectable ECM scaffold for diabetic wound repair.

Public transcriptomic datasets from human diabetic foot ulcers were reanalyzed to assess ECM remodeling- and growth factor-related gene expression patterns and enriched wound repair-associated pathways. Full-thickness excisional wounds were then created on the dorsum of streptozotocin (STZ)-induced diabetic mice and treated with perilesional microinjections of UFM-hADM or saline. Wound closure was assessed by digital planimetry. Wound tissues were analyzed by histology, immunohistochemistry, and quantitative reverse transcription-polymerase chain reaction.

Human diabetic foot ulcer datasets showed increased expression of several matrix metalloproteinase family members, altered ECM- and growth factor-related transcripts, and enrichment of tissue remodeling-associated pathways. In STZ-induced diabetic mice, UFM-hADM significantly improved wound closure compared with saline treatment, with near-complete epithelial coverage and more organized granulation tissue by Day 10. UFM-hADM-treated wounds showed increased expression of Col1a1, Col3a1, Tgfb1, and Egf, whereas Mmp1 and Mmp3 expressions were reduced. Immunohistochemistry showed increased CD31-positive microvessel density and α-smooth muscle actin-positive myofibroblast staining.

Human diabetic foot ulcer transcriptomic profiles support ECM remodeling and growth factor-related signaling as disease-associated features of chronic diabetic wounds. UFM-hADM improved wound repair in STZ-induced diabetic mice, with increased angiogenesis, reduced MMP expression, altered ECM-related gene expression, and more organized granulation tissue formation. These findings support further evaluation of UFM-hADM as an injectable human-derived ECM scaffold for chronic diabetic wounds.