Beyond Antibiotics. Bioactive Glass and Antimicrobial Peptide against Orthopedic Infections

Orthopedic implant-associated infections (OIAIs), particularly those caused by Staphylococcus aureus , are difficult to treat due to biofilm formation and reduced antimicrobial susceptibility. This thesis investigated local antimicrobial strategies based on bioactive glass (BAG) S53P4 and the synthetic antimicrobial and antibiofilm peptide SAAP-148 to prevent and combat biomaterial-associated infections. A novel injectable BAG S53P4 cream demonstrated rapid and broad antimicrobial activity against planktonic bacteria, biofilms, multidrug-resistant pathogens, and fungi, and effectively inhibited S. aureus outgrowth in a cadaver bone defect model. Mechanistic studies showed that BAG S53P4 eluates exert bactericidal activity through a stepwise process involving ionic imbalance, membrane damage, loss of membrane potential, protein delocalization, metabolic disruption, cytoplasmic leakage, cell wall degradation, and silicon deposition on and within bacterial cells. To enhance activity against high bacterial loads and biofilms, SAAP-148 was incorporated into BAG putty and cream. These formulations eradicated planktonic and biofilm-associated S. aureus and Acinetobacter baumannii in vitro and showed enhanced efficacy in cadaver and in vivo mouse implant infection models. In parallel, SAAP-148-loaded poly(ester amide) coatings were developed for titanium implants. These coatings provided sustained or rapid peptide release depending on the coating method and demonstrated robust bactericidal activity against S. aureus . Overall, this thesis advances the understanding and development of BAG S53P4-based formulations and SAAP-148 delivery systems as complementary local antimicrobial approaches for preventing and treating orthopedic biomaterial-associated infections, supporting their further development toward clinical application.

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