Developing an antimicrobial release strategy using nanoclay gels to treat osteomyelitis

骨髓炎定义为骨和骨髓的炎症和感染，由微生物侵入和感染骨组织引起（1）。主要病原体是金黄色葡萄球菌，一种革兰氏阳性球菌，是大多数皮肤和软组织感染的原因（2）。细菌可以通过三种主要途径进入骨骼：i）骨折或外科手术造成的创伤（3）ii）通过菌血症感染源自血流（1）或iii）从周围软组织感染传播（4）。主要治疗是抗生素，可以在治疗后4 - 6周内清除急性感染（5）。慢性骨髓炎是一种更复杂的疾病表现，通常需要静脉注射抗生素以及手术干预以成功根除感染（6）。需要开发新的治疗选择来治疗骨髓炎，因为长期使用全身抗生素不方便，可能导致不良副作用，如肾毒性，并且由于全身性、长期暴露于抗生素，可能增加抗菌素耐药菌株的数量（7）。已经开发了局部抗生素给药策略，包括使用聚甲基丙烯酸甲酯（PMMA）和硫酸钙骨水泥，但这些都有其自身的局限性，包括PMMA的不可生物降解性，导致复发性感染（8）。纳米粘土凝胶由盘形纳米颗粒形成，其在水中自组装为水凝胶（9）。纳米粘土水凝胶已经显示出作为生物活性分子结合和定位生长因子的支架的有希望的结果，从而形成刺激组织再生的微环境（10）。该项目将测试纳米粘土凝胶作为治疗骨髓炎的潜在抗生素递送系统。本综述将提供骨髓炎的详细概述，包括疾病的特征标志，微生物病因学，目前的治疗方案，并介绍一种新的纳米粘土凝胶技术，旨在将纳米粘土的骨再生特性与局部抗生素递送结合联合收割机，以帮助骨愈合。

Osteomyelitis is defined as inflammation and infection of the bone and bone marrow and is caused by microorganisms invading and infecting bone tissue (1). The main causative agent is staphylococcus aureus, a Gram-positive coccus bacterium that is responsible for most skin and soft tissue infections (2). Bacteria can gain entry to bone via three main routes i) trauma inflicted by a fracture or surgical procedure (3) ii) originate from the bloodstream via a bacteraemia infection (1) or iii) spread from surrounding soft tissue infection (4). The mainstay treatment is antibiotics, which can clear acute infections within 4-6 weeks of treatment (5). Chronic osteomyelitis is a more complex manifestation of the disease which usually requires a course of intravenous antibiotics as well as surgical intervention for successful eradication of infection (6). There is a need for developing new therapeutic options to treat osteomyelitis as prolonged use of systemic antibiotics is inconvenient, can result in adverse side effects such as nephrotoxicity, and can increase the number of antimicrobial resistant strains due to systemic, prolonged exposure to antibiotics (7). Localised antibiotic delivery strategies have been developed including the use of polymethyl methacrylate (PMMA) and calcium sulphate bone cements however these have their own limitations including the non-biodegradable nature of PMMA leading to recurrent infection (8). Nanoclay gels are formed from disk shaped nanoparticles, that self-assemble as a hydrogel in water (9). Nanoclay hydrogels have shown promising results as a scaffold for bioactive molecules to bind to, and localise growth factors, resulting in the formation of microenvironments that stimulate tissue regeneration (10). This project will test nanoclay gels as a potential antibiotic delivery system for treatment of osteomyelitis. This review will provide a detailed overview of osteomyelitis including characteristic hallmarks of disease, microbial aetiology, current treatment options, and introduce a novel nanoclay gel technology that aims to combine the bone regenerative properties of nanoclays with localised antibiotic delivery to aid bone healing.