Prevention of murine implant-associated infection by SAAP-148-loaded bioactive glass S53P4 formulation

Introduction Orthopedic implant-associated infections are difficult to treat due to bacterial persistence in biofilms on implant surfaces and in surrounding tissues. Bioactive glass S53P4 (BAG) is a clinically used bone graft substitute with antibacterial properties resulting from surface reactivity and dissolution-mediated changes in the local microenvironment; however, its antibacterial efficacy against established infections with a high bacterial burden is limited. In this study we therefore developed BAG putty and cream formulations loaded with synthetic antimicrobial and antibiofilm peptide SAAP-148 to enhance local antibacterial activity. Methods Eluates from SAAP-148-loaded and unloaded BAG putty and cream formulations were tested in vitro against planktonic bacteria and biofilms of Staphylococcus aureus and Acinetobacter baumannii . Antibacterial efficacy was further assessed in cadaver mouse subcutaneous implant infection model as an intermediate validation step before evaluation in an in vivo mouse subcutaneous implant infection model using S. aureus . Results In vitro , SAAP-148-loaded BAG putty and BAG cream eluates eradicated planktonic bacteria as well as young and mature biofilms of S . aureus and A . baumannii . Eluates of BAG formulations without SAAP-148 had limited bactericidal activity, with BAG cream eluates slightly more bactericidal than BAG putty eluates. The enhanced antibacterial effects of SAAP-148-loaded BAG formulations were confirmed in a cadaver mouse subcutaneous implant infection model, where S. aureus was eradicated both on the implant surface and in the surrounding tissue, whereas BAG-only formulations showed limited antibacterial effect. In a subsequent in vivo mouse subcutaneous implant infection model, SAAP-148-loaded BAG putty eradicated S. aureus on the implant surface and markedly reduced bacterial burden in tissue, whereas BAG putty-only failed to reduce bacterial numbers. Conclusion Loading SAAP-148 into BAG putty and cream enhanced BAG antibacterial and antibiofilm activity, supporting its potential as a clinically relevant adjunct to the BAG’s antimicrobial activity for treating implant-associated infections.