Dual-Therapy Resorbable Biomaterials to Eliminate Bone Infections and Biofilms

Orthopedic implants can become infected in hospitals requiring additional surgeries and device replacement. The pathogenesis of these device-associated bone infections is fundamentally driven by the transition of opportunistic pathogens from a free-floating planktonic state to a surface-bound, highly resilient biofilm state. Biofilms shield resident bacteria within a self-secreted extracellular polymeric substance (EPS) matrix, making them up to 1000-fold more resistant to conventional systemic antibiotics and host-immune clearance. To overcome the clinical challenges of biofilm elimination, the field of regenerative bone biointerfaces is transitioning from traditional antibiotic therapies toward multifunctional, fully resorbable, dual-therapy biomaterial platforms. These modern architectures are engineered to simultaneously clear localized infections and orchestrate host bone tissue reconstruction within a single surgical window. This review provides a comprehensive categorization and critical evaluation of six breakthrough therapeutic themes shaping next-generation orthopedic scaffolds: (1) spatiotemporally optimized dual or multiple antibiotic delivery networks; (2) integrated antibiotic-osteogenic growth factor/peptide frameworks; (3) mechanistically direct biofilm matrix-disrupting enzyme matrices; (4) localized hyperthermic near-infrared (NIR) photothermal therapy combined with osteogenic scaffolds; (5) intrinsic antibiotic-free antimicrobial metal ion/nanoparticle scaffolds; and (6) alternative biological agent architectures leveraging bacteriophages or probiotic biofilms. This review summarizes the advantages, limitations, clinical potential, and future research directions of each therapeutic platform.