Providing Antimicrobial Property to Surfaces of Ultra High Molecular Weight Polyethylene (Uhmwpe) Via Grafting By Uv Induced Raft Polymerization

Abstract

Annually over 1 million patients in the US receive total joint replacements. Ultrahigh molecular weight polyethylene (UHMWPE) has been used as a load-bearing articular surface in majority of total joint arthroplasty. Periprosthetic infection (PJI) is the most threatening complication facing total joint patients. Although it occurs in 1-2% of cases, PJI is the reason of 30% of revisions and is a severe healthcare burden. Most importantly, PJI is tremendously painful and difficult for the patients. Recurrence of PJI prolongs the hospitalization with additional series of surgeries. With recurrence, treatment becomes less effective, some procedures such as arthrodesis amputation are often performed. Approaches are needed to improve the efficacy of PJI treatment. Irrigation and debridement (I&D), liner exchange, and one-stage revision are currently used options to treat PJI. The gold standard treatment is removal of all components and the placement of antibiotic-impregnated PMMA bone cement in the joint space in a first surgery, followed by the placement of all new implant components after an intended 6-8 weeks of antibiotic treatment. However, the bioavailability of systemic antibiotics in the bone/implant interface is very low and inefficient. On the other hand, patients are largely immobilized during treatment due to PMMA spacers not being able to bear the full weight of the patients. The 5-year success rates of I&D followed by liner exchange and two stage surgery are 38 % and 80 % of the time. As one strategy, therapeutic agents, such as antibiotics, can be incorporated into ultra-high molecular weight polyethylene (UHMWPE) implants typically used in total joint arthroplasty for local delivery of these therapeutic agents. Because of its superior mechanical strength and markedly improved wear resistance in comparison to bone cement UHMWPE is a better candidate than PMMA bone cement as an articulating spacer and a delivery device eluting antibiotic. Two important aspects have vital importance for an effective PJI treatment; appropriate dosage control and sustainable antibiotic treatment. They both require great attention otherwise could be devastating for patients and eventually turned into an immense public health problem. Antibiotic dosage control must be so delicate that it is not above toxicity levels and not below MIC which could lead to antibiotic resistance. Sustainable antibiotic release is essential for implants to avoid bacterial colonization which will fail patients to an additional joint replacement surgery. Therefore, it is vital to tailor a drug-releasing implant which ensures delicate dosage control and sustainable antibiotic release. The aim of this thesis is to functionalize nonpolar UHMWPE by grafting 2-hydroxyethyl methacrylate monomer and blend resulting copolymer (UHMPWE-g-PHEMA) with commonly used antibiotic, gentamicin sulfate. RAFT polymerization was also used to synthesize UHMWPE-g-PHEMA with controlled the molecular weight and the molecular weight distribution of PHEMA to control the rate and the sustainability of gentamicin sulfate release. Alterations in the chemical properties after grafting PHEMA to UHMWPE have been investigated by using surface characterization methods, ATR-FTIR, elemental analysis, X-ray photoelectron spectroscopy (XPS), contact angle. Subsequently, antibiotic release studies from antibiotic-loaded UHMWPE and UHMWPE-g-PHEMA (prepared by conventional polymerization or RAFT polymerization) were conducted. Antimicrobial efficacy of said polymers was tested in two ways: 1. Planktonic kill in the eluent media, 2. Anticolonizing properties of polymeric surfaces. Synthesized/prepared drug loaded polymers were tested to evaluate their mechanical strength and wear resistance by using tensile testing, IZOD impact testing and pin-on-disc wear testing. The graft copolymer of UHMWPE-g-PHEMA showed significant increase for the GS release rate in comparison to virgin UHMWPE. The antibacterial performance of UHMWPE-g-PHEMA became more effective in parallel with release rate improvement. HEMA grafting from UHMWPE reduced its mechanical properties such as ultimate tensile strength, elongation at break and IZOD impact strength. UHMWPE-g-PHEMA synthesized via UV-initiated RAFT polymerization increased the GS release rate in a more sustainable trend compared to copolymer prepared via conventional grafting. Thus, UHMWPE-g-PHEMA exhibited better planktonic bacterial kill and non-adherent surface.