Dual-Functional Porous UHMWPE Implant Eliminates <i>Staphylococcus aureus</i> Infection and Induces Osteogenesis in a Critical-Sized Segmental Femoral Defect Model in Mice

<i>Staphylococcus aureus</i> is one of the main causes of osteomyelitis. The problem of antibiotic resistance is particularly acute in osteomyelitis because, in most cases, <i>S. aureus</i> forms biofilms in which the antibiotic sensitivity of bacteria is significantly reduced, and more than 50% of osteomyelitis cases are associated with methicillin-resistant <i>S. aureus</i> (MRSA). One of the promising approaches for surgical treatment of osteomyelitis caused by <i>S. aureus</i> may be one-stage replacement of the affected fragment with a spongy scaffold that provides both a bactericidal effect, particularly in relation to antibiotic-resistant <i>S. aureus</i>, and osseointegration of the implant. This work describes the preparation and characterization of porous ultrahigh-molecular-weight polyethylene (UHMWPE) scaffolds with incorporated microparticles of the silicate ceramic diopside, carrying recombinant bone morphogenetic protein 2 (BMP-2) as an osteogenic component and lysostaphin as an antibacterial component effective against MRSA strains. The hybrid implant had an optimal pore size and kinetics of recombinant protein release and demonstrated bactericidal and high osteointegrative properties using an <i>in vivo</i> model with implantation of blocks of the material into a segmental defect of critical size (4 mm) complicated with <i>S. aureus</i> infection in mice. In terms of its physical parameters, porous UHMWPE/Diopside is as close to spongy bone tissue as possible compared to other polymeric materials while being bioinert and nonresorbable. The addition of BMP-2 led to a 5-fold increase in the volume of newly formed bone tissue (BV/TV), while the presence of <i>S. aureus</i> completely suppressed this effect. The presence of lysostaphin made it possible to overwhelm the infection, achieve regeneration parameters, and restore a normal load distribution on the limbs after 8 weeks. In combination with recombinant BMP-2 and lysostaphin, porous UHMWPE/Diopside can be considered a promising material for the replacement of extensive infected bone tissue defects, particularly in the nonload-bearing areas.