Pre-establishing an IMRC-seeded living biointerface coordinates infection control and osseointegration

Periprosthetic joint infection (PJI) compromises osseointegration through bacterial colonisation and dysregulated inflammation. Here, we pre-established a living biointerface by seeding immunity-and-matrix-regulatory cells (IMRCs) onto three-dimensional (3D)-printed titanium prostheses modified with silver (Ag) by plasma immersion ion implantation (Ag-PIII) before bacterial exposure, generating an IMRC-seeded Ag-PIII-modified titanium (TAM) construct. TAM was associated with reduced bacterial attachment. The Ag-PIII-modified substrate achieved antibacterial efficiencies above 99% against Staphylococcus aureus and Escherichia coli while supporting IMRC viability and attachment. TAM-conditioned medium favoured an M2-like macrophage profile, and enhanced osteogenic differentiation of bone marrow mesenchymal stem cells. In the beagle PJI model, TAM reduced bacterial recovery and peri-implant inflammation and improved bone formation, fixation strength, and locomotor performance at 8 weeks. These findings provide preclinical support for pre-establishing an IMRC-seeded living biointerface to alter the initial conditions of surface competition and integrate early infection control with subsequent osseointegration.