Developing an antimicrobial release strategy using nanoclay gels to treat osteomyelitis

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.