Angiogenesis and re-epithelialization are critical factors in skin wound healing. Growth factors and stem cells have demonstrated their active roles in promoting these two processes. Peptides show similar effects with growth factors with lower cost and controllable properties. Here we report a biomimetic fragment of the laminin –Ser-Ile-Lys-Val-Ala-Val (SIKVAV)-conjugated chitosan hydrogel that can promote skin regeneration. In vitro we found that this peptide-conjugated hydrogel significantly promoted BMSC adhesion and proliferation. In vivo, this hydrogel accelerated wound contraction. The subcutaneous implantation test and H&E staining results revealed that the peptide-modified chitosan hydrogel dramatically led to the formation of new blood vessels. Moreover, Masson staining showed that many newborn collagen fibers appeared in the peptide hydrogel group, while only a few newborn collagen fibers were found in control and chitosan hydrogel groups. The peptide chitosan hydrogel also re-epithelialized quickly, while the control and chitosan hydrogel took more time to complete. These results suggest that the SIKVAV peptide is an effective motif to significantly improve the function of chitosan in angiogenesis and re-epithelialization of skin.
Cutaneous wound healing following trauma is a complex and dynamic process involving multiple overlapping events following trauma. Two critical elements affecting skin wound healing are neovascularization and inflammation. A nascent vessel can provide nutrition and oxygen to a healing wound. Therefore, treatments strategies that enhance angiogenesis and inhibit inflammation can promote skin wound healing. Previous studies have shown that the SIKVAV peptide (Ser-Ile-Lys-Val-Ala-Val) from laminin can promote angiogenesis in vitro . This study evaluated the effects of peptide SIKVAV-modified chitosan hydrogels on skin wound healing. We established skin wounds established in mice and treated them with SIKVAV-modified chitosan hydrogels. H&E staining showed that peptide-modified chitosan hydrogels accelerated the reepithelialization of wounds compared with the negative and positive controls. Immunohistochemistry analysis demonstrated that more myofibroblasts were deposited at wounds treated with peptide-modified chitosan hydrogels that at those treated with negative and positive controls. In addition, peptide-modified chitosan hydrogels promoted angiogenesis as well as keratinocyte proliferation and differentiation, but inhibited inflammation in skin wounds. Taken together, these results suggest that SIKVAV-modified chitosan hydrogels are a promising treatment component for healing-impaired wounds.
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