Recent Advances in the Evaluation of Antimicrobial Materials for Resolution of Orthopedic Implant-Associated Infections In Vivo

Abstract

While orthopedic implant-associated infections are rare, revision surgeries resulting from infections incur considerable healthcare costs and represent a substantial research area clinically, in academia, and in industry. In recent years, there have been numerous advances in the development of antimicrobial strategies for the prevention and treatment of orthopedic implant-associated infections which offer promise to improve the limitations of existing delivery systems through local and controlled release of antimicrobial agents. Prior to translation to in vivo orthopedic implant-associated infection models, the properties (e.g., degradation, antimicrobial activity, biocompatibility) of the antimicrobial materials can be evaluated in subcutaneous implant in vivo models. The antimicrobial materials are then incorporated into in vivo implant models to evaluate the efficacy of using the material to prevent or treat implant-associated infections. Recent technological advances such as 3D-printing, bacterial genomic sequencing, and real-time in vivo imaging of infection and inflammation have contributed to the development of preclinical implant-associated infection models that more effectively recapitulate the clinical presentation of infections and improve the evaluation of antimicrobial materials. This Review highlights the advantages and limitations of antimicrobial materials used in conjunction with orthopedic implants for the prevention and treatment of orthopedic implant-associated infections and discusses how these materials are evaluated in preclinical in vivo models. This analysis serves as a resource for biomaterial researchers in the selection of an appropriate orthopedic implant-associated infection preclinical model to evaluate novel antimicrobial materials.

Keywords: Antibiotic; Drug delivery; Implant; In vivo; Periprosthetic joint infection.

Figure 1.

Summary of recent advances in implant-associated infection preclinical in vivo models used to simulate the clinical environment of infections. Models have utilized emerging technologies of 3D-printing and bacterial genomic sequencing to improve the clinical relevancy of the model and to analyze the role of patient risk factors on the development of implant-associated infections. Figure created using BioRender.com.

Figure 2.

Setup of ex vivo PMMA bone cement push-out testing model using bovine femur tissue. Small, uniform wafers of bovine femur were machined from a cleaned/bleached femur segment (a) with eight 5/32 in. holes spaced 0.3 in. apart (b). Holes in the femur wafer were packed with PMMA materials, and a 1/8 in. steel pin was used to push embedded PMMA out of the femur wafer under compressive force at a loading rate of 20 mm/min (c). “Pushed-out” PMMA specimen from femur wafer (d). Representative raw force versus displacement plot of interfacial shear strength of PMMA pushed-out of a single 5/32 in. hole (e). Images were taken by the authors.