Heparin sodium enriched gelatin/polycaprolactone based multi-layer nanofibrous scaffold for accelerated wound healing in diabetes

Abstract

Multilayered nanofibrous scaffolds (MNSs) obtained by electrospinning have gained widespread attention owing to their control over the delivery of drugs. However, polymer and drug solubility issues in common solvent systems still limit their applications. The present work employed acetic acid : water : ethyl acetate (4 : 4 : 2 v/v/v) as a common solvent system for dissolving gelatin and heparin sodium (HS). A GL 20% w/v solution showing optimum viscosity and conductivity, and high encapsulation (89.2 ± 2.13%) was selected. Additionally, TPGS-1000 incorporated in GL reduced the surface tension for better electrospinning and additional free-radical scavenging activity (∼6 fold of blank nanofibers). The central layer was surrounded by upper and lower PCL–GL layers to control the release of the hydrophilic drug (HS). The electrospun PCL : GL layer sustained the release for ∼24 hours. The developed multilayered nanofibrous scaffolds showed accelerated wound healing in a diabetic rat model. Histological analysis of the wound confirmed the accelerated re-epithelialization and reduced inflammatory response. Laser Doppler flowmetry further showed a significant improvement in the blood flow at the wound site at day 14 and day 21, revealing neovascularization. Therefore, the developed multilayered nanofibrous scaffolds provided a plausible method for fabricating regenerative scaffolds for drug delivery and diabetic wound healing.