OICC Press Progress in Biomaterials 2194-0517 14 04 2025 12 31 Dual-Layer Sponge–Nanofiber Construct Enabling Sustained Sitagliptin Release for Enhanced Diabetic Wound Healing 10.57647/pibm.2025.1404.62 EN Roya Hesari Asl Department of Biomedical Engineering, CT.C., Islamic Azad University, Tehran, Iran Shahrokh Shojaei Department of Biomedical Engineering, CT.C., Islamic Azad University, Tehran, Iran Mohammad Narimani Rad Department of Biomedical Engineering, CT.C., Islamic Azad University, Tehran, Iran Azadeh Asefnejad Department of Biomedical, Engineering, SR.C., Islamic Azad University, Tehran, Iran Milad Jafari-Nodoushan Department of Biomedical Engineering, CT.C., Islamic Azad University, Tehran, Iran Journal Article 2025 12 31 Diabetic wounds pose a major challenge due to impaired healing, infection risk, and poor vascularization. A Dual-layer biomimetic wound dressing was designed to integrate structural and biochemical functionalities for advanced wound management. The upper layer consisted of a sponge matrix based on polyacrylic acid and poly(allylamine hydrochloride), embedded with sitagliptin-loaded fucoidan–chitosan nanoparticles, enabling exudate absorption and sustained drug release. The lower layer comprised electrospun silk fibroin nanofibers, closely mimicking extracellular matrix architecture. Characterization was performed using SEM and FTIR. The dressing demonstrated a swelling ratio of 512.2% in distilled water and degradation of 38.2% after 7 days immersion in PBS. Sustained sitagliptin release reached 82.4% over 7 days. Mechanical evaluation revealed tensile strength of 354.0 KPa, elastic modulus of 987.6 KPa, and elongation of 171.3%, which was adequate for wound healing applications. In vitro assays confirmed superior L929 fibroblast viability on the Dual-layer dressing, with the nanofibrous layer supporting extensive adhesion and spreading. In vivo studies in a diabetic rat model showed enhanced re-epithelialization, organized collagen bundles, improved early-stage angiogenesis, and reduced inflammation, resulting in nearly complete wound healing within 14 days. These findings indicate that the Dual-layer dressing provides a promising strategy for diabetic wound healing.