Zhao Xingchen, Zhai Dong, Jell Gavin, Wu Chengtie, Gao Huiling, Jones Julian R
Department of Materials, Imperial College London, South Kensington Campus, London, UK.
State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Dingxi Road 1295, Shanghai, China.
Acta Biomater. 2025 Aug;202:605-621. doi: 10.1016/j.actbio.2025.06.033. Epub 2025 Jun 19.
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-30CaO-15BO (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.
糖尿病伤口的再生受到功能失调的细胞外基质（ECM）形成、血管生成受损和炎症持续时间延长的阻碍。我们报告了通过优化改良的溶胶-凝胶静电纺丝参数制备的首批硼酸盐含量超过2摩尔%、硼酸盐含量高达70摩尔%的硼硅酸盐生物活性玻璃（BG）纳米纤维伤口基质。所得的三维基质模仿细胞外基质纤维的形态，纤维直径均匀，为100-300纳米，可随着治疗性钙离子、硼酸盐和硅酸盐物质的释放而生物降解。重点是研究硼酸盐含量对体外细胞反应的影响，以确定最佳的硼硅酸盐组成；55SiO-30CaO-15BO（摩尔%，55S30C15B）基质促进成纤维细胞产生最大量的血管内皮生长因子和碱性成纤维细胞生长因子，并导致内皮细胞的代谢活性、蛋白质表达和迁移受到最高程度的刺激。我们的体内研究（小鼠糖尿病模型）证实了55S30C15B伤口基质在改善伤口闭合、抗炎反应、血管生成、组织肉芽形成（α-平滑肌肌动蛋白）和胶原蛋白沉积方面的功效，同时阐述了硼酸盐和纳米纤维结构的不同作用。所有证据表明，我们的基质在糖尿病伤口再生方面具有巨大潜力。重要性声明：我们开发了一种用于伤口愈合的新型支架；首批硼酸盐含量超过2摩尔%、硼含量高达70摩尔%的硼硅酸盐BG纳米纤维（100 - 300纳米）垫。我们确定了纤维递送的硼酸盐剂量对成纤维细胞和内皮细胞的影响。在体内模型中，模仿ECM的支架结构在伤口愈合级联反应的所有阶段均显示出功效。
