SURFACE MODIFIED METALLIC ORTHOPEDIC IMPLANT FOR SUSTAINED DRUG RELEASE

Abstract

Artificial hip implants are used to provide stability or replace damaged bone tissue, enhance physical mobility and improve the quality of life. Despite the advances in orthopedic surgery, high sterilization and developments in antibiotic prophylaxis, implant related infections still remain a formidable challenge to researchers and surgeons. These infections play pivotal role in aseptic loosening of implant. As a result, implants fail prematurely and leads to the suffering of tens of thousands of patients every year. Besides, the second surgery is also required to remove the infected implant, increasing the economic burden and chances of patient mortality. Considering the potential repercussions of implant associated infections, preventing the infection is the most logical way than treating the infection after its emergence. Therefore, it is essential to prevent the infection at the initial level by supplying the required amount of antibiotics around the implantation site, within the first few days after the surgery. However, with all precautions in place also, infection still can occur in some cases at a later stage. Thus, it is also important to have the antibiotics available at the implant site for long duration, though in a controlled manner to restrict over-exposure. Hence the main objective of present research work is to develop the surface modified metallic orthopaedic implant system, which will release the drug locally in a sustained manner for a longer duration, while retaining its bioactivity, and mechanical performance as per requirement. In line with this, the present research work is divided into three major parts. In the first part of study, surface engineering of the currently used metallic implants was done without compromising their mechanical properties. To achieve this, FDA approved plasma spraying technique is utilized to synthesize interconnected microporous bioactive hydroxyapatite (HA) coating on the Ti-6Al-4V implant surface. The modified implant surface is impregnated with drug (gentamicin) loaded biodegradable polymer (chitosan) through a customized vacuum impregnation process. During impregnation, drug loaded polymer filled the pores of coating while leaving the rest of the HA surface exposed to promote osteoconductivity. The hardness and elastic modulus of the HA coating showed insignificant changes after impregnation with the drug loaded polymer, while the fracture toughness is improved by ∼42%. In vitro drug release studies have revealed a sustained release up to 180 h, with an ideal initial burst release. The drug loaded surfaces have also shown very efficient antibacterial activity against S. aureus, even after 5 days of incubation. Further, the modified surfaces have shown excellent osteocompatibility, due to the presence of the exposed HA coated surface. Thus, the surface modified implants, with a unique combination of antibacterial activity, osteocompatibility, and improved fracture toughness, have promising potential applications in orthopedics. In the second part of the study, the main aim was to improve the total duration of drug release, while keeping the mechanical attributes of the coating to the satisfactory level. This led to the introduction of the gradient porosity (multilayer HA coating) concept, aimed to have more pores (porosity) available for more drug loading while maintaining mechanical attributes of coating at a satisfactory level. Typically, multilayer HA coating features a gradient of porosity that varies from bottom to top in different layers. A thin dense HA layer, adjacent to Ti alloy substrate offers strong adhesion with the implant surface, while the gradient increase in porosity on the upper layers maintain the integrity of the coating, allowing the loading of drug in higher quantity. Developed coating is filled with drug containing biodegradable polymer through vacuum impregnation method. This structure offered an improvement in drug loading by 145% and increased the drug release duration (in hour) by almost 4 times compared to single layer dense coating (drug loading: 11 μg/mm2 and drug release up to: 170 h). In addition to these, effective filling of the pores with polymer improved the fracture toughness of the HA coating significantly, by restricting the crack growth. Improved tribological behavior was also noted, along with excellent bioactivity and osseointegration.