Electrospun Polycaprolactone/Gelatin Blended Nanofibre Textiles with Controlled Dexamethasone Release for...

The performance of drug-loaded electrospun nanofibres is governed not only by drug content but also by the spatial distribution of the drug within the fibre matrix, which determines release kinetics and biological response. Here, we demonstrate that dose-dependent surface crystallisation of dexamethasone (DEX) in electrospun polycaprolactone (PCL)/gelatin nanofibres controls drug release behaviour and subsequent macrophage-mediated inflammation. Nanofibre mats containing 0, 1, and 2 wt% DEX (PG0, PG1, PG2) were fabricated and systematically characterised. Scanning electron microscopy revealed a change from homogeneous fibres (PG0) to surface-decorated crystalline domains with increasing drug loading, which indicates a supersaturation-driven phase separation during electrospinning. This morphological evolution directly governs the transport behaviour: PG2 exhibits a pronounced burst release due to surface-localised drug, whereas PG1 shows a balanced release profile with both surface-accessible and matrix-embedded drug fractions. Release characteristics result in different biological outcomes. PG1 and PG2 strongly inhibit pro-inflammatory cytokines (TNF-α and IL-6) in LPS-stimulated macrophages (~70-75% reduction), confirming retained drug bioactivity. However, higher drug loading (PG2) leads to lower fibroblast viability and compromised mechanical integrity. Importantly, PG1 shows a desirable balance of controlled drug release, cytocompatibility (>90% viability) and mechanical performance (~8 MPa) with effective anti-inflammatory activity. Degradation studies also show controlled structural evolution without destabilisation upon pH change, demonstrating suitability for wound environments. These results reveal surface crystallisation as an important design parameter for electrospun drug delivery systems and demonstrate that optimal therapeutic performance is controlled by intermediate drug loading, not maximum loading, providing a mechanistic framework for the rational design of immunomodulatory wound dressings.