Highly Adherent Antimicrobial Coatings for Orthopedic Implants

Author

Mikhail BredikhinFollow

Date of Award

12-2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Bioengineering

Committee Chair/Advisor

Alexey Vertegel

Committee Member

Robert Latour

Committee Member

Agneta Simionescu

Committee Member

Narendra Vyavahare

Abstract

Fracture-related infections (FRIs) are the most devasting sort of complications associated with fracture fixation devices, as they lead to patients’ morbidity, prolonged hospitalization, amputations, and even death.External fixators additionally suffer from pin site infections (PSIs), which initiate at the skin entry points of the skin-metallic pin interface present in the external fixation of the damaged bones, often causing deep tissue infection and osteomyelitis. Small percutaneous pins, commonly known as Kirschner wires (K-wires), are used to treat complex fractures and deformities.They are drilled inside the diseased bone for the healing period and are left protruding outside the skin for fixation adjustments and easy removal. Metal surface of the K-wires, however, provides an anchor for the pathogens to adhere and migrate underneath the skin toward the bone, where they can form biofilms and become resistant to oral and intravenous antibiotics. While the incidence rate of PSIs has been reported to reach 100%, there is still limited literature regarding the prevention of PSIs and the overall lack of pin site-specific research.Despite the significant improvements in post-surgical aseptic technique, there is no consensus on either optimal antimicrobial dressing for the post-operative period or burying K-wires under the closed skin wound.

Drug-releasing surface coatings of the implants is the recently emerged trend to address clinicallyimportant issues such as prophylaxis of microbial infections and reduction of inflammatory response. Some orthopedic implants, however, are subjected to large shear forces, which remove or damage any weakly adhered physiosorbed coatings. Hence, little progress has been made on drug-releasing coatings for those implants. Our research, therefore, aims to fill that gap on the drug-eluting orthopedic implants and the modeling of their abrasion-resistance properties.

In this study, we have developed two types of highly adhesive drug-releasing coating: the synthetic Poly(glycidyl methacrylate) (PGMA)-based polymeric brush and the natural chitosan coatings. Derived from the shells of crustaceans, chitosan is a linear polysaccharide molecule that is generally recognized as safe by FDA and is currently pending approval for drug delivery applications. Furthermore, chitosan has been shown to possess antimicrobial activity against a wide variety of microorganisms, produce films with good mechanical properties, and stimulate new bone formation.The synthetic (PGMA)-based copolymer, on the other hand, is a branched molecule that consists of three individual monomers: glycidyl methacrylate (GMA) - a cross-linkable monomer with epoxy group which can form stable permanent network; a hydrophilic oligoethylene glycol methacrylate (OEGMA), which provides compatibilization with water; and a hydrophobiclauryl methacrylate (LMA), which provides amphiphilic balance to the resulting macromolecule.

We hypothesized that our developed drug-loaded coatings would retain antimicrobial properties after drilling into compact bone or its mimetic and would be superior to the plain drug and the drug-loaded commercial Poly(DL-lactide) (PLA) coatings. The objective of this study was to validate this platform technology for drug-eluting orthopedic implants with specific focus on K-wires because of the high incidence of infections for these devices.

In the first part of the dissertation, we prepared and characterized two types of coatings, chitosan-based and PGMA-based. By varying matrix composition parameters of the polymer and drug loading we identified the optimal formulations capable of resisting shear forces during K-wire drilling in vitro.

In the second part of the dissertation, we characterized antimicrobial efficacy of the best-performing coatings before and after the drilling. The findings of this aim helped us to choose the optimal coating for the pilot in vivo study. We conducted the animal study which confirmed the effectiveness of the applied highly adherent antimicrobial coating.

Recommended Citation

Bredikhin, Mikhail, "Highly Adherent Antimicrobial Coatings for Orthopedic Implants" (2022). All Dissertations. 3184.
https://tigerprints.clemson.edu/all_dissertations/3184