3D-printed porous titanium rods equipped with vancomycin-loaded hydrogels and polycaprolactone membranes for intelligent antibacterial drug release

Abstract

Abstract Implant-related infections pose significant challenges to orthopedic surgeries due to the high risk of severe complications. The widespread use of bioactive prostheses in joint replacements, featuring roughened surfaces and tight integration with the bone marrow cavity, has facilitated bacterial proliferation and complicated treatment. Developing antibacterial coatings for orthopedic implants has been a key research focus in recent years to address this critical issue. Researchers have designed coatings using various materials and antibacterial strategies. In this study, we fabricated 3D-printed porous titanium rods, incorporated vancomycin-loaded mPEG750-b-PCL2500 gel, and coated them with a PCL layer. We then evaluated the antibacterial efficacy through both in vitro and in vivo experiments. Our coating passively inhibits bacterial biofilm formation and actively controls antibiotic release in response to bacterial growth, providing a practical solution for proactive and sustained infection control. This study utilized 3D printing technology to produce porous titanium rod implants simulating bioactive joint prostheses. The porous structure of the titanium rods was used to load a thermoresponsive gel, mPEG750-b-PCL2500 (PEG: polyethylene glycol; PCL: polycaprolactone), serving as a novel drug delivery system carrying vancomycin for controlled antibiotic release. The assembly was then covered with a PCL membrane that inhibits bacterial biofilm formation early in infection and degrades when exposed to lipase solutions, mimicking enzymatic activity during bacterial infections. This setup provides infection-responsive protection and promotes drug release. We investigated the coating’s controlled release, antibacterial capability, and biocompatibility through in vitro experiments. We established a Staphylococcus aureus infection model in rabbits, implanting titanium rods in the femoral medullary cavity. We evaluated the efficacy and safety of the composite coating in preventing implant-related infections using imaging, hematology, and pathology. In vitro experiments demonstrated that the PCL membrane stably protects encapsulated vancomycin during PBS immersion. The PCL membrane rapidly degraded at a lipase concentration of 0.2 mg/mL. The mPEG750-b-PCL2500 gel ensured stable and sustained vancomycin release, inhibiting bacterial growth. We investigated the antibacterial effect of the 3D-printed titanium material, coated with PCL and loaded with mPEG750-b-PCL2500 hydrogel, using a rabbit Staphylococcus aureus infection model. Imaging, hematology, and histopathology confirmed that our composite antibacterial coating exhibited excellent antibacterial effects and infection prevention, with good safety in trials. Our results indicate that the composite antibacterial coating effectively protects vancomycin in the hydrogel from premature release in the absence of bacterial infection. The outer PCL membrane inhibits bacterial growth and prevents biofilm formation. Upon contact with bacterial lipase, the PCL membrane rapidly degrades, releasing vancomycin for antibacterial action. The mPEG750-b-PCL2500 gel provides stable and sustained vancomycin release, prolonging its antibacterial effects. Our composite antibacterial coating demonstrates promising potential for clinical application.

Keywords

• 3D printing
• Titanium
• Infection
• Vancomycin
• PCL
• PEG