Unravelling the effect of metal ions leaching from bioactive glasses on wound associated biofilms

慢性创面的特点是形成稳定而顽固的生物膜，阻碍先天免疫反应，延迟或阻止伤口愈合。由于抗药性细菌的增加，寻求不依赖抗生素作用的新的治疗策略是势在必行的。本项目将研究3D纤维生物活性玻璃(BG)中金属离子浸出破坏病原生物膜并帮助慢性伤口愈合的潜力和机制。这将通过在BGS和BG纳米纤维上进行体外和体内研究以及组织与材料的相互作用来实现。具体地说，BGS的抗微生物和抗生物膜特性将在临床相关细菌上进行测试。此外，还将测试BGS对上皮细胞的细胞毒性作用，以确保BGS可以安全使用，最后，将通过在小鼠模型和体外人类伤口中测试BGS来研究BGS的伤口愈合特性。作为补充，将建立偏微分方程式的数学模型。该模型旨在捕捉啮齿动物伤口和体外人体伤口的离子释放率、抗菌效果和体内愈合情况，其中模型参数将根据实验数据进行估计。这个数学模型将有助于更好地理解伤口愈合和微生物生物膜清除过程中涉及的复杂和非线性相互作用，同时也产生了一种工具，可以用来预测从离子释放率和抗菌活性方面有效伤口愈合的BGS的最佳组成。

Chronic wounds are characterised by a stable and stubborn biofilm which hinders innate immune response and delays or prevents wound healing. Due to the rise in antibiotic resistant bacteria it is imperative that novel treatment strategies, that do not rely on antibiotic action, are sought. This project will investigate the potential and mechanism via which metal ion leaching from 3D fibrous bioactive glass (BG) disrupts pathogenic biofilms and aids in the healing of chronic wounds. This will be done by conducting in vitro and in vivo studies and tissue-material interactions on BGs and BG-nanofibres. Specifically, antimicrobial and antibiofilm properties of the BGs will be tested on clinically relevant bacteria. Additionally, cytotoxic effects of the BGs on epithelial cells will be tested to ensure that the BGs may be safe to use and finally, the wound-healing properties of the BGs will be investigated by testing the BGs in murine mouse models and ex vivo human wounds. Complementary to the above, a partial differential equation mathematical model will be developed. This model will aim to capture the ion release rate, antimicrobial effects and in vivo healing of rodent wounds and ex vivo human wounds, where the model parameters will be estimated from experimental data. This mathematical model will facilitate an improved understanding of the complex and nonlinear interactions involved in wound healing and the clearance of microbial biofilms, whilst also generating a tool that can be exploited to predict optimum composition of BGs for effective wound healing with respect to ion release rates and antibacterial activity.