SimultaneousDelivery of Multiple Antibacterial Agents from Additively ManufacturedPorous Biomaterials to Fully Eradicate Planktonic and Adherent Staphylococcusaureus

摘要

Implant-associated infections are notoriously difficult to treat and may even result in amputation and death. The first few days after surgery are the most critical time to prevent those infections, preferably through full eradication of the micro-organisms entering the body perioperatively. That is particularly important for patients with a compromised immune system such as orthopedic oncology patients, as they are at higher risk for infection and complications. Full eradication of bacteria is, especially in a biofilm, extremely challenging due to the toxicity barrier that prevents delivery of high doses of antibacterial agents. This study aimed to use the potential synergistic effects of multiple antibacterial agents to prevent the use of toxic levels of these agents and achieve full eradication of planktonic and adherent bacteria. Silver ions and vancomycin were therefore simultaneously delivered from additively manufactured highly porous titanium implants with an extremely high surface area incorporating a bactericidal coating made from chitosan and gelatin applied by electrophoretic deposition(EPD). The presence of the chitosan/gelatin (Ch+Gel) coating, Ag,and vancomycin (Vanco) was confirmed by X-ray photoelectron spectroscopy(XPS) and Fourier transform infrared spectroscopy (FTIR). The releaseof vancomycin and silver ions continued for at least 21 days as measuredby inductively coupled plasma (ICP) and UV-spectroscopy. Antibacterialbehavior against Staphylococcus aureus, both planktonic and in biofilm, was evaluated for up to 21 days.The Ch+Gel coating showed some bactericidal behavior on its own, whilethe loaded hydrogels (Ch+Gel+Ag and Ch+Gel+Vanco) achieved full eradicationof both planktonic and adherent bacteria without causing significantlevels of toxicity. Combining silver and vancomycin improved the releaseprofiles of both agents and revealed a synergistic behavior that furtherincreased the bactericidal effects.