Development and Study of Antibacterial <i>In situ</i> Coatings for Processing Implants

Abstract

Introduction. Periprosthetic infections are a major problem in orthopedic surgery. The most optimal way to influence the bacterial film is to suppress the early stages of its formation. The use of hydrogel coatings for the prevention of periprosthetic infections is an effective measure, while the process of coating the implant can be simplified due to the use of in situ systems.Aim. The purpose of the research is to develop and study antibacterial in situ coatings for preoperative treatment of implants.Materials and methods. In the experiment we used poloxamers Kolliphor® P 407 and Kolliphor® P 188 (BASF, Germany), hyaluronic acid high-molecular PrincipHYAL® (1400–1800 kDa), low-molecular PrincipHYAL® (400–600 kDa), mixture of high, medium and low-molecular acids PrincipHYAL® Cube3 (ROELMI HPC Srl, Italy). As screening methods for identifying the optimal composition, we used gelation temperature measurements, pH measurements, studies of rheological properties, and microbiological tests.Results and discussion. During the experiment, we found the optimal concentration of hyaluronic acid 1400–1800 kDa – 0.5 %, at which the studied composition at a temperature of 4.5 ± 0.5 °C was a homogeneous liquid, and it made a sol-gel transition when heated. It was revealed that hyaluronic acid had no significant effect on the gelling temperature, so we added poloxamer 188. We also established the influence of the hyaluronic acid molecular weight on the in situ systems characteristics. High molecular weight hyaluronic acid stabilized the viscosity values and improved the adhesive properties of the system, samples with medium and low molecular weight hyaluronic acid showed lower dynamic viscosity values at the phase gel-sol transition end. We tested the optimal composition (containing 18.0 % poloxamer 407, 2 % poloxamer 188, and 0.5 % hyaluronic acid (1400–1800 kDa) adhesion to the titanium plate. When exposed to the paddle stirrer (rotation speed 20 rpm) for 15 minutes and stored in the thermostat (37,0 ± 0,5 °C) for a week, the analyzed composition showed adhesion strength, which makes it possible to use it for coating.Conclusion. By multistage screening a sample was selected for introduction of a model antibacterial component representing a cocktail of bacteriophages Klebsiella pneumonia, Staphylococcus aureus, Escherichia coli. Microbiological studies showed good compatibility of the immunobiological substance with excipients, which indicated the prospects for further preclinical studies.

Keywords

• <i>in situ</i> gelling
• implant coating
• periprosthetic infections
• hyaluronic acid
• poloxamer
• bacteriophages