Microneedle-Mediated Delivery of Extracellular Matrix-Inspired Peptides for Mitigation of Burn Wound Progression and Support of Tissue Repair.

Topical treatment of burn wounds remains challenging because eschar formation, inflammation and impaired vascularization can limit drug penetration and tissue repair. Here, we introduce a flexible large-area microneedle patch for sustained local delivery of extracellular matrix-derived peptides to deep partial-thickness burn wounds. The microneedles were composed of cellulose acetate phthalate and hydroxypropyl methylcellulose and included a transparent water-soluble backing layer to aid placement and allow dissolution after application. The patch delivered two peptides with previously reported biological activity: TSN6, associated with angiogenic responses and TSN18, associated with cell proliferation and epithelial repair. The microneedles retained sharp conical geometry after peptide loading, showed sufficient compressive strength for skin insertion and produced consistent microchannels in ex vivo porcine skin. In vitro studies showed peptide-dependent release over 48 h: TSN18 reached approximately 50% release within 12 h and exceeded 80% release by 48 h, whereas TSN6 was released more slowly, reaching 45% when loaded alone and 58% when co-loaded with TSN18. In a porcine deep partial-thickness burn model, TSN18-treated wounds showed lower burn depth than SSD-treated wounds at day 4 (1174 ± 35 vs. 1628 ± 178 μm, p < 0.05). Co-delivery of TSN6 and TSN18 preserved more dermis than the scrambled peptide control (1667 ± 134 vs. 938 ± 194 μm, p < 0.05) and increased neoepidermal thickness at day 20 compared with scrambled peptide and SSD controls (417 ± 45 vs. 237 ± 25 and 265 ± 16 μm, respectively). Although consistent improvements in macroscopic wound closure and re-epithelialization were not observed across peptide-treated groups, these results show that microneedle-mediated peptide delivery can improve selected tissue-level measures of burn injury and epidermal repair.