Laminin mimetic angiogenic and collagen peptide hydrogel for enhance dermal wound healing

Laminins are essential in basement membrane architecture and critical in re-epithelialization and angiogenesis. These processes and collagen deposition are vital in skin wound healing. The role of angiogenic peptides in accelerating the wound-healing process has been known. The bioactive peptides could be a potential approach due to their similar effects as growth factors and inherent biocompatible and biodegradable nature with lower cost. They can also recognize ligand-receptor interaction and mimic the extracellular matrix. Here, we report novel angiogenic DYVRLAI, CDYVRLAI, angiogenic-collagen PGPIKVAV, and Ac-PGPIKVAV peptides conjugated sodium carboxymethyl cellulose hydrogel, which was designed from laminin. The designed peptide exhibits a better binding with the α₃β₁, α_vβ₃, and α₅β₁ integrins and CXCR2 receptor, indicating their angiogenic and collagen binding efficiency. The peptides were evaluated to stimulate wound healing in full-thickness excision wounds in normal and diabetic mice (type II). They demonstrated their efficacy in terms of angiogenesis (CD31), re-epithelialization through regeneration of the epidermis (H&E), and collagen deposition (MT). The synthesized peptide hydrogel (DYVRLAI and CDYVRLAI) showed enhanced wound contraction up to 10.1 % and 12.3 % on day 7^th compared to standard becaplermin gel (49 %) in a normal wound model. The encouraging results were also observed with the diabetic model, where these peptides showed a significant decrease of 5.20 and 5.17 % in wound size on day 10^th compared to the commercial gel (9.27 %). These outcomes signify that the modified angiogenic peptide is a cost effective, novel peptide motif to promote dermal wound healing in both models.