Investigating in Vitro-in Vivo Correlations in Bacterial Behaviour to Design Antibiotic-Eluting Implants for Periprosthetic Joint Infection Management

Periprosthetic joint infection (PJI) is a debilitating condition which significantly affects the clinical outcome of arthroplasty. Staphylococcus spp., the predominant causative organism, resists antibiotic treatments and evades the host immune response by forming complex biofilms 1 . Although extensive studies have characterized Staphylococcal biofilms in vitro , the growth dynamics and severity of biofilms in vivo are poorly understood 2 . Our overarching goal is to devise antibacterial tools in the form of medical devices and long-acting drug delivery devices to prevent and treat PJI. To this end, we have developed antibiotic-eluting ultrahigh molecular weight polyethylene (UHMWPE), which has the potential to not only deliver antibiotics locally but to improve the functional recovery of PJI patients 3,4,5 . We established a subcutaneous implant infection model in the rat model using methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) and analyzed implant capsule tissues across multiple time points (POD0, POD1, POD3, POD7) using RNA bulk sequencing. Differential gene expression, KEGG and GO enrichment, ssGSEA, and CIBERSORTx analyses were employed to identify diagnostic markers and characterize immune cell infiltration profiles. Additionally, immune profiling was conducted on a public dataset related to clinical orthopedic implant infections to determine overlaps in transcriptional pathways. The comparison and stratification of the risk and severity of infection across different preclinical models can guide clinical dosing and the design of antibacterial implants to effectively prevent or treat PJI. Here, we are going to present our material work in controlling the release rates of local antibiotics and synergistic non-antibiotic molecules 6 and our work on bacterial 7 and host characterization in vivo (including our transcriptomics above) and in vitro to determine clinical dosing guidance and administration timelines for these antibacterial implants. )