DEVELOPING POLYMER BASED SURFACE MODIFIED COMPOSITE FOR DRUG ELUTING ORTHOPEDIC IMPLANTS

Abstract

Osteoarthritis is a degenerative joint disease, caused due to wear and breaking down of the bone cartilage in a joint. Prosthetic joint replacement is the only solution after all non-surgical treatments fail to resolve the issue. Joint replacement alleviates the pain and restores the function of joints, improving the activeness in the patients. However, even after decades of successful track record, ~10% of these implant fail prematurely, within the first 10 to 20 years, thereby affecting many tens of thousands of patients annually. These premature failures lead to revision of surgeries. Aseptic loosening, fracture and implant associated infection are the main causes of arthroplasty failures. Despite sterilization and aseptic procedure, bacterial infection remains a key challenge in total hip arthroplasties. This fact emphasizes the urgent need for development of new implant systems, which should take care the infection by delivering the drug locally and improve structural stability to minimize the implant loosening and fracture. Hence, the major aim of the present investigation is to modifying the surfaces of polymeric acetabular cup liner for sustain delivery of drugs, while retaining the mechanical and tribological properties of clinically used ultra-high molecular weight polyethylene (UHMWPE) joint prostheses. The present work mainly includes four major parts. In first part of the study, modified solvent based etching and lyophilization technique was used to engineer a thin porous surface layer on UHMWPE (PE) substrate, which is clinically used as acetabular cup lining. Gentamicin contained chitosan solution has been impregnated into modified surface, which suitably gets released over a long period. The main challenge was to keep the mechanical and tribological behavior of this lining material unaffected after the modification. Modified surface offers reduction in friction coefficient and wear rate, by 26% and 19%, respectively, in comparison to PE, which is encouraging towards the intended application. Hardness and elastic modulus decreases slightly, by 27% and 20%, ii respectively, possibly due to improper impregnation of chitosan inside porous surface. However, after drug release, the modified surface regains the mechanical and tribological behavior similar to unmodified PE. Surface modified PE have shown an impressive release profile for drug up to 26 days and released ~94.11% of the total drug content. In vitro antibacterial tests have proven that the modified surface of PE can effectively release the drug and fight against infection. Besides, positive outcome of in-vitro cell culture shows potential of this material system in intended application. In second part, electrostatic spray coating technique was used to construct the thin interconnected micro porous coating on PE substrate. Coating integrity, after curing, is expected to be good by considering the similarity in coating and substrate material. Uniform and deep pores were observed throughout the surface. Surface morphology on drug delivery kinetics, antibacterial efficacy, mechanical and tribological behavior was discussed extensively. This technique was compared with the former (modified solvent based etching technique) and competitive salient features of both were identified. Both the modified surfaces have shown slight decrease in hardness and elastic modulus, which may be attributed to improper impregnation of polymer inside porous surface. However, after the release of drug, the solvent-based etched surfaces regain its mechanical and tribological properties, in similar range to the unmodified PE surface, but not in case of electrostatic spray coating. Besides, the surfaces, modified by both techniques, have shown lower friction coefficient. But, higher wear rates were noticed for electrostatic sprayed coating. On the other hand, the drug release duration (860 h) was more for electrostatic spray modified surface than chemical etched surface (624 h). In third part, an attempt has been made to improve the basic properties of conventional PE liner by preparing CNT-PE composite, to address issue related to decrease in mechanical property during surface modification of liner. CNTs are the great choice as reinforcement to prepare bio-composite because of its high in-plane-stiffness and strength, which helps in iii toughening agent. Besides, their weaker out-of-plane integrity offers solid lubrication mechanism. Two different aspect ratios of CNTs, namely high aspect ratio (HAR-900) and low aspect ratio (LAR-75) ones were reinforced with PE matrix. A nominal 0.05–0.1 wt.% of CNT addition increases the hardness and elastic modulus of PE by 3–45% and 8–42%, respectively. Higher aspect ratio CNTs (HARCs) are found more effective in improving hardness (45%) and modulus (42%) of PE composite. On the other hand, significant improvement in tribological and thermal degradation property was also noticed for HARCs than LARCs (low aspect ratio CNTs) composite. Reasons for better performance of HARCs are their morphological similarity with polymer chains. The composite, containing 0.1 wt.% HARC have shown best mechanical and tribological behavior. In fourth part, modified solvent based etching technique is used to engineer thin porous surface layer on 0.1 wt.% reinforced HARC composite. Modified test sample have shown an impressive gentamicin release profile up to 492 h (21 days). Around 89% of the total drug content got released in sustainable manner. Where as in surface modified PE, gentamicin released up to 624 h (26 days) and ~94.11% of the total drug content got released. The difference is directly related to surface morphology. In vitro antibacterial examination (Disc Diffusion Test) had proven the efficacy of drug release to eradicate the bacteria around the sample. Besides, modified surfaces of the HARC composite have shown reduction in friction coefficient and specific wear rate by 36% and 20%, respectively, as compared to PE. This was attributed due to improved mechanical properties of CNTs and their self-lubricating mechanism. Even after drug release, the mechanical and tribological properties of CNT-PE composite are much better than PE. In-vitro cytocompatibility results are also encouraging towards its intended application. Hence, these surfaces modified CNT-PE composite sample has shown great promise for fighting against initial infection after surgery. iv The surface engineered acetabular cup lining is a promising candidate in the area of drug eluting implant, which can bring a significant advancement to the functionality of commercially used orthopedic implants by providing inherent capacity for fighting against infections in-vivo.