Introduction: Diabetic wounds are challenging to treat due to a wide range of pathophysiological changes. Hypoxia is one of the predominant contributing factors of poor vascularization and chronicity in diabetic wounds. This study was designed to develop polycaprolactone (PCL)-based oxygen-releasing electrospun wound dressings and evaluate their efficacy for improved full thickness wound healing in diabetic rats. Methods: PCL-based oxygen releasing wound dressings were made using electrospinning technology. The developed dressings were characterized in terms of physical as well as biological properties both in vitro and in vivo. E-spun nanofibrous dressings were physically characterized with scanning electron microscopy, Fourier-transform infrared spectroscopy, and Energy-dispersive X-ray spectroscopy. To study the likely impact of the fabricated wound dressings in hypoxic conditions, HIF-1α expression analysis was carried out both at gene and protein levels. Wound dressings were further evaluated for their healing potential for extensive wounds in diabetic rat models. Results: The experimental results showed that the developed dressings were capable of continuously generating oxygen for up to 10 days. Cell studies further confirmed pronounced expression of HIF-1α at gene and protein levels in cells seeded on PCL-sodium percarbonate (SPC) and PCL scaffolds compared with the cells cultured on a tissue culture plate. Chorioallantoic membrane assay revealed the supportive role of oxygen releasing dressings on angiogenesis compared to the control group. Histological assessment of the regenerated skin tissues proved that full thickness wounds covered with SPC loaded PCL dressings had a comparatively better vascularized and compact extracellular matrix with completely covered thick epithelium. Discussion: The developed oxygen generating polymeric nanofibrous wound dressings could potentially be used as an envisioned approach for the efficient recovery of chronic diabetic wounds.

Following recent work from our group on a small ribose-derived sugar 2-deoxy-d-ribose which stimulates angiogenesis in a chick chorionic allantoic membrane bioassay and in skin wounds in healthy rats, we tested the effect of this sugar when added to a common alginate wound dressing in a well-accepted diabetic skin wound model in rats. Dressings were simply loaded with filter-sterilized sugar solutions that were proved stable at room temperature for at least two weeks. Prior to undertaking the animal study, we assessed in vitro release of sugar loaded from alginate dressings loaded with either 5 or 10% 2-deoxy-d-ribose. Both showed more than 90% release of sugar over three days followed by a lesser and sustained release for up to eight days. Diabetes was induced in rats by streptozotocin injection followed by confirmation through measuring elevated blood glucose levels all over the period of the study. Full thickness skin wounds of 20 mm diameter showed slow healing and were still unhealed at 20th day in the control animals. The addition of alginate hydrogel did significantly stimulate wound healing compared to the untreated animals, but the addition of 2-deoxy-d-ribose at either 5 or 10% further and significantly improved the rate of wound healing. The most striking result was seen in the effect of sugar on angiogenesis in the wound beds where alginate alone did not improve the extent of CD34 identified blood vessels in the wound beds but the addition of sugar significantly increased these – this could be seen as early as seven days post addition of the sugar-loaded alginate dressing and was still evident at day 20. Thus, these results suggest that the controlled use of 2-deoxy-d-ribose could be a novel and cost-effective therapy for the management of impaired wound healing in diabetic patients.

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Background Following recent findings from our group that curcumin preconditioning augments the therapeutic efficacy of adipose-derived stem cells in the healing of diabetic wounds in rats, we aimed to investigate the regenerative effects of curcumin preconditioned adipose-derived mesenchymal stem cells (ASCs) for better recovery of acid inflicted burns in this study. Methods ASCs were preconditioned with 5 μM curcumin for 24 hours and assessed for proliferation, migration, paracrine release potential and gene expression comparative to naïve ASCs. Subsequently, the healing capacity of curcumin preconditioned ASCs (Cur-ASCs) versus naïve ASCs was examined using acidic wounds in rats. For this, acid inflicted burns of 20 mm in diameter were made on the back of male Wistar rats. Then, 2 × 106 cells of Cur-ASCs and naïve ASCs were intradermally injected in the wound periphery (n = 6) for comparison with an untreated saline control. Post-transplantation, wounds were macroscopically analysed and photographed to evaluate the percentage of wound closure and period of re-epithelization. Healed wound biopsies were excised and used for histological evaluation and expression analysis of wound healing markers at molecular level by quantitative PCR and western blotting. Results We found that Cur-ASCs exhibited greater proliferation, migration and paracrine potential in vitro. Further, Cur-ASCs showed more effective recovery than naïve ASCs as exhibited by gross morphology, faster wound closure and earlier re-epithelialization. Masson’s trichrome and hematoxylin and eosin staining demonstrated the improved architecture of the healing burns, as evidenced by reduced infiltration of inflammatory cells, compact collagen and marked granulation in Cur-ASC treated rats. Corroborating these findings, molecular assessment showed significantly reduced expressions of pro-inflammatory factors (interleukin-1 beta, interleukin-6, tumor necrosis factor alpha) a with striking upsurge of an oxidative marker (superoxide dismutase 1), pro-angiogenic factors (vascular endothelial growth factor, hepatocyte growth factor, hypoxia-inducible factor-1 alpha) and collagen markers (transforming growth factor beta 1, fibroblast growth factor-2, collagen type 1 alpha 1), verifying that Cur-ASCs modulate the regulation of pro-inflammatory and healing markers at burn sites. Conclusions Treatment with Cur-ASCs resulted in faster re-epithelization of acid inflicted burns compared to the treatment with naïve ASCs. Based on observed findings, we suggest the transplantation of Cur-ASCs is a valuable therapy for the potent clinical management of acidic burns.