Enhanced skin regeneration in diabetic wounds using collagen-hyaluronic acid scaffold incorporated with epigallocatechin gallate: a multifactorial healing approach.

Diabetic wounds pose significant clinical challenges owing to delayed healing associated with chronic inflammation, impaired angiogenesis, and poor extracellular matrix (ECM) remodeling. Bioengineered scaffolds incorporating natural bioactives offer promising strategies for enhancing skin regeneration. In this study, the author developed and evaluated a collagen-hyaluronic acid (Col-HA) scaffold loaded with epigallocatechin gallate (EGCG), a polyphenolic compound known for its antioxidant, anti-inflammatory, and proangiogenic properties. EGCG was incorporated into porous Col-HA scaffolds, and their physicochemical properties, degradation rate, and drug release profile were characterized. In vitro cell viability assays were performed using mesenchymal stem cells to assess biocompatibility. A full-thickness excisional wound model was established in streptozotocin-induced diabetic rats, which were treated with control (no scaffold), Col-HA scaffold, EGCG alone, or Col-HA + EGCG scaffolds. Wound healing was evaluated on days 7 and 14 via macroscopic closure, histological stereology (epidermal/dermal volume and fibroblast and vascular density), cytokine profiling (transforming growth factor (TGF)-β, vascular endothelial growth factor (VEGF), interleukin (IL)-1β, and tumor necrosis factor (TNF)-α), hydroxyproline quantification, and tensile strength testing. The EGCG-loaded Col-HA scaffold exhibited a porous microstructure (~ 120 µm pore size) and a biphasic release profile, with sustained EGCG release up to 14 days. In vivo, the Col-HA + EGCG group demonstrated significantly accelerated wound closure compared with other groups (p < 0.05). Histological analysis revealed enhanced regeneration of epidermis and dermis, increased fibroblast proliferation and angiogenesis, and reduced inflammatory cell infiltration. ELISA results showed upregulated TGF-β and VEGF levels and downregulated IL-1β and TNF-α in the Col-HA + EGCG group. Moreover, collagen content and tensile strength were highest in this group, indicating superior ECM remodeling and mechanical restoration. The multifunctional Col-HA scaffold incorporated with EGCG effectively promotes diabetic wound healing by modulating inflammation, enhancing angiogenesis, and supporting tissue regeneration. This combinatorial strategy holds significant potential for advanced wound care therapies.