Department of Biomedical Engineering, University of Connecticut, Storrs, CT, 06269, USA.
Department of Mechanical Engineering, University of Connecticut, Storrs, CT, 06269, USA.
Biomaterials. 2023 Oct;301:122270. doi: 10.1016/j.biomaterials.2023.122270. Epub 2023 Aug 8.
Electrical stimulation (ES) induces wound healing and skin regeneration. Combining ES with the tissue-engineering approach, which relies on biomaterials to construct a replacement tissue graft, could offer a self-stimulated scaffold to heal skin-wounds without using potentially toxic growth factors and exogenous cells. Unfortunately, current ES technologies are either ineffective (external stimulations) or unsafe (implanted electrical devices using toxic batteries). Hence, we propose a novel wound-healing strategy that integrates ES with tissue engineering techniques by utilizing a biodegradable self-charged piezoelectric PLLA (Poly (l-lactic acid)) nanofiber matrix. This unique, safe, and stable piezoelectric scaffold can be activated by an external ultrasound (US) to produce well-controlled surface-charges with different polarities, thus serving multiple functions to suppress bacterial growth (negative surface charge) and promote skin regeneration (positive surface charge) at the same time. We demonstrate that the scaffold activated by low intensity/low frequency US can facilitate the proliferation of fibroblast/epithelial cells, enhance expression of genes (collagen I, III, and fibronectin) typical for the wound healing process, and suppress the growth of S. aureus and P. aeruginosa bacteria in vitro simultaneously. This approach induces rapid skin regeneration in a critical-sized skin wound mouse model in vivo. The piezoelectric PLLA skin scaffold thus assumes the role of a multi-tasking, biodegradable, battery-free electrical stimulator which is important for skin-wound healing and bacterial infection prevention simultaneuosly.
电刺激（ES）可诱导伤口愈合和皮肤再生。将 ES 与组织工程方法相结合，该方法依赖于生物材料来构建替代组织移植物，可为治愈皮肤伤口提供自我刺激的支架，而无需使用潜在有毒的生长因子和外源性细胞。不幸的是，目前的 ES 技术要么无效（外部刺激），要么不安全（使用有毒电池的植入式电气设备）。因此，我们提出了一种新的伤口愈合策略，该策略通过利用可生物降解的自充电压电 PLLA（聚（L-乳酸））纳米纤维基质将 ES 与组织工程技术相结合。这种独特，安全且稳定的压电支架可以通过外部超声（US）激活，以产生具有不同极性的可控制表面电荷，从而同时具有抑制细菌生长（负表面电荷）和促进皮肤再生（正表面电荷）的多种功能。我们证明，通过低强度/低频 US 激活的支架可以促进成纤维细胞/上皮细胞的增殖，增强与伤口愈合过程相关的基因（I 型、III 型胶原和纤维连接蛋白）的表达，并同时抑制金黄色葡萄球菌和铜绿假单胞菌在体外的生长。这种方法可在体内大尺寸皮肤伤口小鼠模型中诱导快速的皮肤再生。因此，压电 PLLA 皮肤支架充当具有多功能，可生物降解，无需电池的电刺激器，这对于皮肤伤口愈合和预防细菌感染很重要。
