Diabetic foot ulcers are chronic, frequently non-healing wounds driven by persistent inflammation and high infection risk. The study aimed to create a biodegradable, extracellular matrix–mimicking wound dressing with anti-inflammatory function to modulate local inflammation and support cell proliferation and migration in diabetic wounds. The approach combined an anti-inflammatory small molecule, 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), with a biocompatible scaffold derived from porcine small intestinal submucosa (SIS).
The anti-inflammatory drug 15d-PGJ2 was encapsulated within poly(lactic-co-glycolic acid) (PLGA) nanoparticles. Characterization of the prepared nanoparticles reported an average hydrodynamic diameter of 261.6 nm, a zeta potential of −14.3 mV, and a polydispersity index (PDI) below 0.2, indicating a relatively narrow particle size distribution. These physico-chemical parameters were used to assess colloidal stability, surface charge properties, and homogeneity of the nanoparticle formulation.
Entrapment efficiency and drug loading were measured for the 15d-PGJ2–PLGA NPs, with values reported as 96.7% entrapment efficiency and 18.5% drug loading, respectively. Release testing indicated that approximately 50% of the encapsulated drug was released within 240 minutes under the reported in vitro conditions. These metrics provide initial evidence of efficient drug incorporation and a release profile consistent with an early-phase burst or sustained release depending on experimental conditions.
To evaluate biocompatibility and inform dosing for scaffold integration, cellular studies were performed. MTT assays assessed mitochondrial activity as a proxy for cell viability in the presence of nanoparticles, while scratch (wound-healing) assays evaluated effects on cell migration. These in vitro assays aimed to determine a safe nanoparticle dose that does not compromise cell viability and that permits or promotes cell migration, which is essential for wound closure.
Porcine SIS sheets were used as the extracellular matrix–mimicking scaffold. The SIS was chemically cross-linked using EDC/NHS (1‑ethyl‑3‑(3‑dimethylaminopropyl)carbodiimide/N‑hydroxysuccinimide) chemistry to modify the scaffold’s stability and mechanical properties prior to nanoparticle integration. Cross-linking is intended to reduce rapid enzymatic degradation and to improve mechanical strength while preserving scaffold biocompatibility.
The 15d-PGJ2-loaded PLGA NPs were incorporated into the EDC/NHS-cross-linked SIS sheets to create the composite wound dressing. Fourier-transform infrared spectroscopy (FTIR) was performed on the modified scaffolds as part of the in vitro characterization to identify chemical signatures associated with cross-linking and nanoparticle incorporation.
A series of in vitro tests characterized the physicochemical behavior of the modified SIS scaffolds. Enzymatic degradation assays quantified scaffold stability and demonstrated a low degradation rate for the cross-linked, nanoparticle-laden constructs. Swelling behavior and water adsorption capacity were assessed, with results showing suitable water uptake consistent with a hydrophilic surface as measured by contact angle analysis. Mechanical testing indicated enhanced mechanical strength after EDC cross-linking and nanoparticle integration compared with native SIS.
Cell adhesion studies were performed to evaluate how fibroblast cells interact with the modified scaffolds. The integrated EDC-crosslinked SIS carrying anti-inflammatory NPs showed effective interaction with fibroblast cells, supporting cell adhesion. These findings suggest that the composite scaffold provides a biologically permissive surface for cells relevant to wound repair.
The EDC-crosslinked SIS scaffold loaded with 15d-PGJ2-containing PLGA nanoparticles combined favorable physicochemical attributes — including controlled drug loading and release, hydrophilicity, low degradation rate, and improved mechanical strength — with compatible biological interactions such as maintained cell viability, migration potential, and fibroblast adhesion. Based on these in vitro results, the authors conclude that the modified SIS scaffold carrying anti-inflammatory NPs exhibits promising characteristics and can be considered a candidate for further evaluation as a therapeutic option for diabetic wound healing.
Note: Details beyond those reported in the source abstract, such as quantitative results of the cellular assays, specific FTIR spectral peaks, exact enzymatic conditions, or in vivo data, were not provided in the source and are therefore not reported here.