Aloin-loaded trilayer PCL/PVA/PCL nanofibrous wound dressing with controlled drug release and enhanced angiogenic activity

Chronic wounds represent significant challenges due to impaired angiogenesis, prolonged inflammation and poor tissue regeneration. This study introduces novel sandwich-like trilayer electrospun wound dressing composed of polycaprolactone (PCL) as outer layers and Aloin-loaded PVA/PCL blend as the inner layer. It was designed to address the dual challenges of burst drug release and inadequate vascularization. Electrospinning was employed to fabricate nanofibers with diameter of 200–330 nm and porosity of 45–60%, mimicking the extracellular matrix of skin to promote cell adhesion and nutrient diffusion. The average diameters of PCL and PVA/PCL fibers were 330 nm and 229 nm, respectively, which decreased to 211 nm and 154 nm upon Aloin loading. The wound dressing also demonstrated excellent fluid management properties with water absorption capacities that was significantly enhanced by Aloin incorporation. The water vapor transmission rate was in the range of 2000–2500 g/m 2 /day that was an ideal value for maintaining wound environment moisture. The construct exhibited a biphasic release profile, initially governed by Fickian diffusion, and finally by matrix erosion. The sandwich system reduced the initial burst release by 28% within 24 h, which was 50% lower than that of single layer counterparts. It maintained therapeutic levels over 14 days. The MTT assays showed fibroblastic cell viability above 98% over 14 days, indicating excellent cytocompatibility. The chick embryo chorioallantoic membrane assay confirmed enhanced angiogenesis in the Aloin-loaded dressing. Furthermore, compared with the drug-free control, the Aloin-loaded scaffold significantly enhanced angiogenesis, resulting in increase in area, length and junctions of vessels, demonstrating its potential for accelerating chronic wound healing and tissue regeneration. Altogether, the tri-layer wound dressing combines controlled drug delivery, biological compatibility, and vascular support, suggesting it as a promising candidate for chronic wound care.