Heparinized Collagen Scaffolds Based on Schiff Base Bonds for Wound Dressings Accelerate Wound Healing without Scar

Skin wound healing is a complex process with multiple growth factors and cytokines participating and regulating each other. It is essential to develop novel wound dressings to accelerate the wound healing process. In this study, we developed the heparinized collagen scaffold materials (OL-pA), and the cross-linking reaction was based on the Schiff base reaction between pig acellular dermal matrix (pADM) and dialdehyde low molecular weight heparin (LMWH). Compared with pADM, the OL-pA modified by cross-linking still retained the triple helix structure of native collagen. When the dosage of the OL cross-linking agent was 12 wt %, the cross-linking density of OL-pA was 49.67%, the shrinkage temperature was 75.6 °C, the tensile strength was 14.62 MPa, the elongation at break was 53.14%, and the water contact angle was 25.1°, all of which were significantly improved compared with pADM. The cytocompatibility test showed that L929 cells adhered better on the surface of OL-pA scaffolds, and the proliferation ability of primary fibroblasts was enhanced. In vivo experiments showed that the OL-pA scaffolds could better accelerate wound healing, more effectively promote the positive expression of bFGF, PDGF, and VEGF growth factors, accelerate capillary angiogenesis, and promote wound scarless healing. In summary, the OL-pA scaffolds have more excellent hygrothermal stability, mechanical properties, hydrophilicity, and cytocompatibility. Especially the scaffolds have significant pro-healing properties for the full-thickness skin wound of rats and are expected to be a potential pro-healing collagen-based wound dressing.