3D printed vasculogenic pectin-fucoidan scaffold containing sildenafil-loaded nanomicelles promoted diabetic wound...

Chronic diabetic wounds are marked by impaired angiogenesis, persistent inflammation, and delayed tissue regeneration, making them a critical challenge in clinical practice. Effective healing requires biomaterials that restore vascularization and support cell proliferation and growth. In this context, a 3D-printed scaffold composed of pectin (Pec) and fucoidan (Fc) was fabricated and integrated with sildenafil-loaded nanomicelles (Sf.NMs). Due to the hydrophobic nature of sildenafil, encapsulation in nanomicelles was employed to improve aqueous dispersion and enable controlled release. Scaffold fabrication was carried out using extrusion-based 3D printing, an accessible technique that facilitates bioactive agent incorporation at room temperature. Physicochemical evaluation demonstrated a swelling ratio of 278.1 ± 15.0 % in water and a biodegradation rate of 39.2 ± 2.0 % in PBS after 7 days. Drug release studies showed a sustained profile, reaching 94.7 ± 2.5 % over 11 days. Cytotoxicity assays confirmed well biocompatibility and cell adhesion on the scaffolds. Additionally, the sustained release of sildenafil significantly stimulated angiogenesis in the CAM assay. In vivo evaluation in a diabetic rat wound model revealed reduced inflammation, enhanced re-epithelialization, and improved wound closure. These results highlight the Pec-Fc/Sf.NMs scaffold as a promising biomaterial capable of addressing impaired vascularization and promoting tissue repair in diabetic wound healing.