The biocompatible and antimicrobial properties of Ag-SrPO4-Mg

Abstract

The utilization of novel biomaterials in the field of orthopaedic surgery is ever increasing. Prosthetic joint infections however remain a significant cause of mortality and morbidity for patients undergoing orthopaedic procedures, as well as being a significant economic burden to healthcare systems, with S. aureus, coagulase-negative Staphylococci such as S. epidermidis and Gram-negative bacilli such as E. coli and P. aeruginosa being the most common offending organisms. Therefore, biomaterials that are bioactive, biodegradable and prevent infection are required. In addition, the host capsular tissue response to prosthetic joint infections at a genetic level, which ultimately culminates in septic loosening around the prosthesis, requires further understanding. This study sought to examine the anti-bacterial and bioactive effects of a novel biomaterial, Ag-SrPO4-Mg. This study tested Ag-SrPO4-Mg against the aforementioned four bacterial species using LIVE/DEAD viability assay and found that S. aureus, S. epidermidis, E. coli and P. aeruginosa were on average inhibited by 93.38%, 32.09%, 85.8% and 47.69%, respectively, compared to stainless steel. This was further confirmed by scanning electron microscopy whereby the surface of Ag-SrPO4-Mg discs had scant bacterial attachment compared to confluent bacterial attachment on stainless steel. The bioactivity and cytotoxicity of Ag-SrPO4-Mg on primary human osteoblasts was tested using ALP assay as well as mineralization assay. We tested 24-hour, 48-hour, 7-day and 14-day extracts of Ag-SrPO4-Mg at concentrations of 10 uL/mL, 1 uL/mL and 0.1 uL/mL. This study did not find a significant reduction in ALP expression or mineralization in osteoblasts treated with Ag-SrPO4-Mg extracts compared to SrPO4-Mg, Mg or PBS controls. The differences that did reach statistical significance have an unclear clinical significance but signified no additional cytotoxicity of Ag-SrPO4-Mg. The project also investigated the gene expression in response to infection by performing RNA extraction, cDNA synthesis and PCR array on capsular tissue obtained from patients at time of primary or reversion arthroplasty. Capsular tissue obtained from patients undergoing revision surgeries for prosthetic joint infections demonstrated significant upregulation of the genes CCL20, CXCL6 and IL27 compared to patients undergoing primary joint replacements at 6.58-fold, 6.81-fold, and 20.98-fold respectively while TNFRSF11B was significantly downregulated by 8.52-fold. The project demonstrated that Ag-SrPO4-Mg is a promising orthopaedic biomaterial in the prevention of prosthetic joint infections while conferring no additional toxicity to host osteoblasts. Show more