Fucoidan-based microneedle patch for delivery of IGF1-loaded exosomes in diabetic wound therapy

Abstract

Diabetic wounds often lead to significant therapeutic challenges due to impaired vascularization, chronic inflammation, and poor drug penetration. This study presents a polyallylamine hydrochloride-fucoidan (PAH.Fc) hydrogel-based microneedle patch for site specific delivery of IGF1-incorporated exosomal vesicles obtained from adipose-derived stem cells (ADSC-Exos) to diabetic wounds. The average size of IGF1-loaded ADSC-Exos was measured as 261.81 nm. The fabricated microneedles exhibited swelling ratios between 228.0 and 247.1, with a degradation rate of 47.56 after 7 days of immersion in PBS. IGF1 release was sustained and time-dependent, reaching 89.25 +/- 4.60 over 168 h. MTT assay confirmed cytocompatibility, with HaCaT cell viability exceeding 80 across all groups. Nile Red labeling demonstrated efficient cellular uptake of both ADSC-Exos and IGF1-loaded ADSC-Exos by HaCaT cells, and CAM assay results revealed that the PAH.Fc/IGF1 Exos induced the highest angiogenic response among tested groups. In vivo studies using a hyperglycemic rat model showed near-complete wound closure within 14 days in the PAH.Fc/IGF1 Exo-treated group, accompanied by elevated expression of VEGF and TGF-beta and reduced levels of pro-inflammatory markers TNF-alpha and IL-1beta. Collectively, these findings demonstrate that the PAH.Fc/IGF1 Exo microneedle patch offers optimized local delivery of bioactive cargo and holds strong therapeutic potential for chronic wound management, particularly in diabetic wound healing.