Injectable Self-Healing Hyaluronic Acid-Collagen Composite Hydrogels for Accelerated Chronic Wound Healing via Sustained Dual Growth Factor Release

This study investigates mechanical and biological performance of injectable self-healing hyaluronic acid-collagen composite hydrogels for sustained PDGF-BB and VEGF dual growth factor delivery in chronic wound healing within the context of biomedical engineering and regenerative medicine, an area of growing scientific importance given its implications for chronic wound management in diabetic ulcers, pressure injuries, and venous leg ulcers. Using rheological characterization, in vitro release kinetics by ELISA, scratch assay keratinocyte migration, and in vivo wound closure rate measurement in db/db diabetic mouse excisional wound model, we examine self-healing dynamic imine crosslinks enabling injectability, with HA hydrophilic network retaining sustained growth factor release while collagen fibril microstructure providing cell adhesion scaffold for fibroblast and keratinocyte migration in 48 db/db diabetic mice (8 per group x 6 groups: control, HA alone, Col alone, HA-Col 1:1, 3:1, 5:1) with 21-day wound closure tracking drawn from full-thickness excisional wounds (6mm biopsy punch) on dorsal skin of db/db diabetic mice housed under barrier conditions. Results indicate that HA-Col 3:1 dual-GF hydrogel achieves 91.4% wound closure at day 21 versus 48.4% in PBS control and 68.4% in collagen-alone scaffold, with 2.4-fold higher vessel density by immunohistochemistry (p < 0.001), with 91.4% wound closure at day 21 vs. 48.4% PBS control as the primary quantitative benchmark. Concordance between primary and confirmatory measurement approaches exceeded 93%, validating the analytical framework. These findings contribute empirically to biomedical engineering and regenerative medicine and carry actionable implications for the design of programs and policies targeting chronic wound management in diabetic ulcers, pressure injuries, and venous leg ulcers.