Borosilicate bioactive glass 3D fibrous matrices with increased borate content stimulate healing cascades in chronic wounds

Diabetic wound regeneration is hindered by dysfunctional extracellular matrix (ECM) formation, impaired angiogenesis and prolonged inflammation. We report the first borosilicate bioactive glass (BG) nanofiber wound matrices with borate content exceeding 2 mol%, achieving up to 70 mol% borate, by optimizing modified sol-gel electrospinning parameters. The resultant 3D matrices mimic the morphology of extracellular matrix fibers with homogeneous fiber diameters of 100-300 nm that can biodegrade with the release of therapeutic calcium ions and borate and silicate species. The focus was investigation of the impact of borate content on cellular response in vitro to identify the optimal borosilicate composition; 55SiO 2 -30CaO-15B 2 O 3 (mol%, 55S30C15B) matrix promoted the greatest expression of vascular endothelial growth factor and basic fibroblast growth factor by fibroblasts and led to the highest stimulation metabolic activity, protein expression and migration of endothelial cells. Our in vivo study (mouse diabetic model) confirmed the efficacy of 55S30C15B wound matrix in improving wound closure, anti-inflammatory response, angiogenesis, tissue granulation (α-SMA), and collagen deposition, while elaborating the distinct roles of borates and nanofiber structure. All evidence suggests that our matrices exhibit great potential for diabetic wound regeneration. Statement of significance We developed a new scaffold for wound healing; the first borosilicate BG nanofiber (100 -300 nm) mats with borate content in excess of 2 mol%, with boron content of up to 70 mol%. We identified the influence of borate dose delivered by the fibers on both fibroblasts and endothelial cells. Efficacy of the ECM-mimicking scaffold structure was shown across all stages of the wound healing cascade in an in vivo model.