SDF-1α and CTGF functionalized Gelatin methacryloyl (GelMA) hydrogels enhance fibroblast activation to promote wound healing

Chronic wound reconstruction is clinically challenging and difficult to manage, attributable to the presence of inert granulation tissue and inactive fibroblasts at the wound site. Although the development of tissue engineering technologies has promoted the development of skin regeneration therapies, their potential is still limited by the functional stability of biological scaffolds as well as the time-consuming and labor-intensive cell culture and seeding protocols. In this study, an effective wound healing dressing composite made of photo-crosslinked gelatin methacryloyl (GelMA) hydrogels loaded with the cytokines stromal cell-derived factor 1α (SDF-1α) and connective tissue growth factor (CTGF) (GelMA-CTGF/SDF-1α hydrogels) was developed to regenerate bioactive granulation tissue. SDF-1α is a potent chemokine that regulates the migration of bone marrow mesenchymal stem cells (BMSCs). CTGF promotes the differentiation of BMSCs into fibroblasts, accelerating the repair of connective tissue defects. Our results show that the GelMA hydrogels exhibits a stable network structure and remarkable biocompatibility to promote a suitable environment for cell adhesion, proliferation, and migration. As a result of its internal pore structure, the GelMA hydrogels can continuously release the loaded SDF-1α and CTGF cytokines. In vitro experiments of GelMA hydrogels loaded with 400 μg/mL SDF-1α and 50 ng/mL CTGF, significantly increased BMSCs recruitment, induced fibroblast differentiation, stimulated fibroblastic pan-markers expression, and increased collagen synthesis. Furthermore, in vivo wound healing studies demonstrated that the GelMA-CTGF/SDF-1α hydrogels dramatically increases the number of BMSCs recruited to the wound area. The expression of fibroblast pan-markers regenerates bioactive granulation tissue and shortens wound healing time. Therefore, the overall results revealed that the GelMA-CTGF/SDF-1α hydrogels are highly efficient in promoting wound healing with a functional structure, mechanical properties and controlled release of cytokines.