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

Abstract 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.