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

慢性伤口的特点是一个稳定和顽固的生物膜，它阻碍先天免疫反应和延迟或阻止伤口愈合。由于抗生素耐药细菌的增加，迫切需要寻求不依赖抗生素作用的新型治疗策略。该项目将研究3D纤维生物活性玻璃（BG）的金属离子浸出破坏致病生物膜并有助于慢性伤口愈合的潜力和机制。这将通过对bg和bg纳米纤维进行体外和体内研究以及组织-材料相互作用来完成。具体而言，BGs的抗菌和抗菌膜特性将在临床相关细菌上进行测试。此外，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离体人体伤口中测试BGs来研究BGs的伤口愈合特性。作为上述的补充，我们将建立一个偏微分方程数学模型。该模型旨在捕捉啮齿动物伤口和人类离体伤口的离子释放率、抗菌作用和体内愈合，其中模型参数将从实验数据中估计。该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BGs的最佳组成，以实现有效的伤口愈合，涉及离子释放率和抗菌活性。

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.