An Injectable Composite Hydrogel of Verteporfin‐Bonded Carboxymethyl Chitosan and Oxidized Sodium Alginate Facilitates Scarless Full‐Thickness Skin Regeneration

Full-thickness skin defect has always been a major challenge in clinics due to fibrous hyperplasia in the repair process. Hydrogel composite dressings loaded with anti-fibrotic drugs have been considered as a promising strategy for scarless skin regeneration. In this work, a hydrogel composite (VP-CMCS-OSA) of carboxymethyl chitosan (CMCS) and oxidized sodium alginate (OSA), with loading anti-fibrotic drug verteporfin (VP), is developed based on two-step chemical reactions. Verteporfin is bonded with carboxymethyl chitosan through EDC/NHS treatment to form VP-CMCS, and then VP-CMCS is crosslinked with oxidized sodium alginate by Schiff base reaction to form VP-CMCS-OSA hydrogel. The characterization by SEM, FTIR, and UV-Vis shows the microstructure and chemical bonding of VP-CMCS-OSA. VP-CMCS-OSA hydrogel demonstrates the properties of high tissue adhesion, strong self-healing, and tensile ability. In the full-thickness skin defect model, the VP-CMCS-OSA composite hydrogels hasten wound healing due to the synergistic effects of hydrogels and verteporfin administration. The histological examination reveals the regular collagen arrangement and more skin appendages after VP-CMCS-OSA composite hydrogel treatment, indicating the full-thickness skin regeneration without potential scar formation. The outcomes suggest that the verteporfin-loaded composite hydrogel could be a potential method for scarless skin regeneration.