Microalgae-derived polyhydroxyalkanoate/PCL composite nanofiber scaffolds for accelerated wound healing in diabetic...

Diabetes mellitus (DM) is a multifactorial metabolic disorder characterized by chronic hyperglycemia due to impaired insulin secretion and/or action. A severe complication is delayed wound healing, particularly diabetic foot ulcers, associated with defective angiogenesis, neuropathy, persistent inflammation, and increased infection risk. Biodegradable, biocompatible biomaterials have gained attention as advanced platforms for tissue regeneration. Polyhydroxyalkanoates (PHAs), microbial-derived biopolymers, are promising for wound healing. This study evaluated the therapeutic efficacy of PHAs derived from high-rate algal pond (HRAP) microalgae using a streptozotocin (STZ)-induced diabetic rat model. HRAP microalgal biomass was used for polyhydroxybutyrate (PHB) extraction via solvent precipitation. Purified PHB was blended with polycaprolactone (PCL) to fabricate electrospun nanofiber scaffolds containing different algal extract concentrations (PHB-1, PHB-2, PHB-3). Structural characterization was performed by NMR and GC-MS. Diabetes was induced in male Wistar rats with a high-fat diet followed by STZ (30 mg/kg). Full-thickness excisional wounds were created and topically treated for 12 days. Wound healing progression was assessed by wound contraction, histopathology, and qRT-PCR analysis of IL-6, TNF-α, and MMP-1. GC-MS confirmed hydroxyalkanoate monomers, validating PHB biosynthesis. Scanning electron microscopy showed uniform, well-defined nanofiber morphology. PHB-based scaffolds significantly accelerated wound closure compared with untreated diabetic controls. Histology revealed enhanced re-epithelialization, dermal regeneration, reduced inflammatory infiltration, and reappearance of hair follicles. Gene expression analysis showed anti-inflammatory effects, with IL-6, TNF-α, and MMP-1 reduced by 67.99%, 74.01%, and 59.60%, respectively. PHB-based nanofiber scaffolds improved diabetic wound healing through combined regenerative and anti-inflammatory actions, supporting sustainable PHB as a promising biomaterial for advanced wound dressings.