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<p>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&#xa0;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&#xa0;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-β and reduced levels of pro-inflammatory markers TNF-α and IL-1β. 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.</p> Graphical abstract <p></p>

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

  • 期刊论文

  • 发表日期：

    2026年7月22日

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  • Marjan Mirhaj,
  • Jaleh Varshosaz,
  • Nada A. Kadhim,
  • Marwa M. Kamil,
  • Maha Hameed Al-bahrani,
  • Mastafa H. Al-Musawi,
  • Sheida Mani,
  • Fariborz Sharifianjazi,
  • Ketevan Tavamaishvili,
  • Mohamadreza Tavakoli,
  • Mina Shahriari Khalaji

摘要

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-β and reduced levels of pro-inflammatory markers TNF-α and IL-1β. 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.

Graphical abstract