Abstract
Skin restoration in patients with diabetes constitutes a significant therapeutic challenge as sustained hyperglycemia interferes with fundamental processes such as angiogenesis, cell regeneration, and inflammation control. These alterations not only delay healing but also increase the risk of infections and complications. Emerging therapeutic strategies such as photothermal irradiation have gained attention for their potential to accelerate tissue repair. In this study, we developed novel three-dimensional (3D)-printed near-infrared (NIR)-responsive scaffolds based on chondroitin sulfate, hyaluronic acid, alginate, and nanofibrillated cellulose, with and without polydopamine photothermal nanoparticles, as a new approach to addressing complex tissue regeneration. The resulting 3D multicomponent scaffolds exhibited suitable morphology, swelling behavior, and biocompatibility for skin wound dressing. An in vitro scratch assay confirmed that the scaffold promotes keratinocyte migration and proliferation. In vivo studies demonstrated that treatment with an NIR-irradiated scaffold accelerated wound closure, leading to narrower scars and a denser dermis in diabetic rats. Notably, complete wound healing occurred 8 days earlier in animals treated with the nanocomposite scaffold under NIR irradiation compared to untreated controls. These findings highlight the therapeutic potential of multifunctional, NIR-responsive biomaterials and establish the proposed 3D-printed nanocomposite scaffold as a promising and innovative platform enhancing skin regeneration in challenging diabetic wound models.