Ultra-fine micronized human dermal matrix reprograms the chronic pressure-ulcer microenvironment to accelerate...

Chronic pressure ulcers persist within a self-sustaining microenvironment marked by unresolved inflammation, inadequate neovascularization, and excessive extracellular-matrix (ECM) degradation, highlighting the need for injectable bioactive scaffolds that can be delivered precisely to reprogram compromised tissue. The ultra-fine micronized human acellular dermal matrix (UFM-hADM; ∼70 μm) is designed to remain suspendable and pass through narrow-gauge injection, enabling uniform distribution along irregular wound margins and undermined tissue planes where sheet-type matrices may have limited contact and conformability. Here, we evaluated perilesional injection of an UFM-hADM (∼70 μm) as an injectable ECM scaffold in a murine cyclic ischemia-reperfusion pressure-ulcer model. Compared to saline, UFM-hADM accelerated early wound closure and improved quality of healing at Day 7, with enhanced re-epithelialization and dermal regeneration accompanied by increased collagen deposition. Mechanistically, UFM-hADM shifted the wound milieu toward a pro-healing program by attenuating pro-inflammatory cytokines (TNF-α and IL-6) while increasing IL-10, promoting neovascularization and vascular maturation (upregulated VEGF, increased CD31 and α-SMA), and restoring balanced ECM remodeling (elevated COL1A1 and COL3A1 with suppression of MMP1 and MMP3). These coordinated molecular changes opposed inflammatory, protease-rich transcriptional signatures identified in human pressure ulcers through public transcriptomic reanalysis. In addition, exploratory observational use of Ministry of Food and Drug Safety (MFDS)-approved UFM-hADM for pressure ulcers, undertaken with patient consent as part of routine clinician-directed care, suggested acceptable tolerability and a favorable healing course during follow-up. Collectively, these findings provide mechanistic support for the adjunctive clinical use of UFM-hADM as a minimally invasive, human-derived injectable ECM adjunct that may facilitate pressure-ulcer healing through coordinated modulation of immune, vascular, and matrix responses.