Photoactivated Gold Nanorod Hydrogel Composite Containing <scp>d</scp>-Amino Acids for the Complete Eradication of Bacterial Biofilms on Metal Alloy Implant Materials

Abstract

Bacterial biofilms associated with orthopedic implants are notorious cell associations of pathogens that show resistance against antibiotic medications and the host immune response. The presence of hard-to-penetrate extracellular polymeric substances in the biofilm provides a protective shield against the different modes of action of conventional antimicrobial agents. To address the severe complications associated with biofilm-related infections in medical implants such as prosthetic joint infections (PJIs), we have developed a treatment approach that is based on a thermoresponsive hydrogel nanocomposite system, containing d-amino acids (D-AAs) and engineered gold nanorods (AuNRs), which can undergo sol-to-gel transformation at physiological temperatures for site-specific sustained drug release. Our two-step approach that utilizes a light-actuated AuNR hydrogel composite system for a combination of photothermal treatment (PTT), following initial biofilm disruption with D-AAs, is filling a current gap to develop alternative therapies that have the potential to advance a whole range of PJI medical treatment technologies. Using this two-step approach, we were able to successfully demonstrate in vitro the effective disruption and total eradication of Staphylococcus aureus biofilms formed on different metal alloys (Ti-based, CoCr, and Ta-based alloys) used in the manufacture of prosthetic joints. Moreover, this nanocomposite treatment is safe, does not lead to thermal damage of the surrounding soft tissues, and is localized to the disruption of the biofilms on the surface of the metal alloys. This treatment modality, when adapted to an open surgical approach that is compatible to current irrigation and debridement (I&D) medical procedures, has great potential to combat chronic PJIs and may help to preserve the implant, thereby decreasing the morbidity and mortality of the alternative revision surgery procedures.