MAGNESIUM BASED BIODEGRADABLE ORTHOPEDIC IMPLANTS

Abstract

The development of temporary biodegradable implants for bone fixation has attracted lots of interest since the last decade. Amongst the material systems used for such implants, magnesium (Mg) has received wide attention in orthopedics due to its biodegradability, suitable mechanical properties and significant biocompatibility. In addition, its low elastic modulus helps in reducing the effect of stress shielding and avoids the chances of secondary surgery which is a limitation in the conventionally used permanent metallic implants (i.e., Stainless Steel, Co-Cr and Ti alloys). Despite these advantages, controlling the severe degradation rate of Mg in an intraosseous (occurring within bone) environment has impeded their frequent application in orthopedics. Hence, there is a need to improve the degradation behavior of Mg along with the improved mechanical and biocompatibility properties. A lot of research has been carried to mitigate the corrosion behavior of Mg to make it a viable biomaterial. This is done primarily through either of the following methods: (i) alloying with other metals; (ii) using a suitable reinforcement for composites and (iii) protective coatings. Thermal sprayed coatings of osteoconductive ceramics, like, hydroxyapatite (HA) have been explored as a potential solution for reducing the corrosion rate of Mg-based substrate. However, limited success is achieved due to the low melting point of Mg, which restricts the ease of fabricating surface-adherent ceramic coating. Thus, a functionally gradient material (FGM) system with Mg core and HA rich surface might solve the limitations of coating on Mg. The FGM consists of different layers for which one has to first the composition of the layers by fabricating the individual composites. Thus, the present work involves fabrication and thorough characterization of individual Mg-based composites reinforced with varying content of HA, fabricated through two different sintering routes (conventional and spark plasma sintering). The main reason behind using HA as a reinforcement is its similar crystallographic structure to the mineral part of the bone. In an attempt, the composites were fabricated via the conventional sintering route, and the mechanical integrity of the composites was evaluated during in vitro exposure. The simulated body fluid (SBF) was chosen as the in vitro medium to evaluate the mechanical integrity of the composites. It has been observed that the addition of 5 wt. % HA decreased the corrosion rate of Mg-3Zn, which in turn maintained the mechanical integrity of the structures even after 14 days of immersion. Mg-3Zn and Mg-3Zn-5HA composites have retained ~ 34 and 66% of ultimate compressive strength after 3 days of immersion. Further, in order to ensure significant biocompatibility, the protein adsorption behavior on composites is also analyzed. It was observed that ~40% more protein was adsorbed by the 5 wt.% HA-reinforced composites (Mg-3Zn-5HA) in 3h, as compared to Mg-3Zn. Adsorption of more proteins on the surface of Mg-3Zn-5HA composites indicates better cell proliferation ability and better corrosion resistance. However, conventional sintering route could ensure only 5 wt. % HA addition to the Mg-3Zn system for best behavior. It was important to look for a suitable fabrication technique, which could have effectively accommodated more HA in the Mg based matrix. Thus, in another attempt, the different HA composition (0, 5, 10, 15 and 20 wt. %) in the Mg-3Zn matrix was added and synthesized via spark plasma sintering route for better consolidation. It has been observed that reinforcement with 15 wt. % HA could increase the corrosion resistance ~ 153 %, as compared to without HA composite. Further, the mechanical properties, such as, hardness and compressive strength improved by ~ 42.8 and 18%, respectively. The immersion studies carried up for 56 days assessed the effect of HA reinforcement in the degradation rate of the Mg-3Zn matrix. The biomechanical stability study indicates that the MZ15H has shown improved mechanical integrity compared to base Mg-3Zn. In connection to this, the semi-empirical model was also developed to predict the mechanical strength of all the composites after certain days of immersion in the physiological environment. Osteoblastic activity has shown better cell proliferation on the composite surfaces reinforced with HA. After optimizing the different layers to be used in FGM, an effort has been taken to fabricate FGM with a compositional gradient of Mg-HA composite through spark plasma sintering. The structure consisted of Mg-3Zn at the core and increasing HA content towards the outer layers. The mechanical properties of the bulk FGM were comparatively better than those of the best individual composite (15 wt. % HA reinforced). More importantly, corrosion resistance of the FGM structure was significantly improved, compared to MZ and MZ15H (15 wt. % HA) monolithic composites. In addition, alkaline phosphatase activity, osteogenic gene expression and cell viability, all indicators of efficient osteogenic differentiation, were enhanced for FGM and 15 wt. % HA reinforced composites.The orthopedic fracture fixing accessories demands final products such as screw plates and pins with different intricate shapes and sizes. Hence, it is challenging to make products from brittle Mg-HA composites. Mg being brittle with limited-slip systems, the addition of HA is expected to make it more brittle. Therefore, there is a considerable need for a bulk-forming process to optimize the parameters such as deformation temperature and strain rate. Thus, the hot deformation behavior was evaluated for the best composition (15 wt. % HA) and compared with the one without HA (MZ). It was found that the flow stress value of the MZ15H composites was higher than the MZ at the temperature range of 300-350°C and strain rate 0.001-1s-1. The activation energy is calculated as 199 kJ/mol for the MZ15H composite and is almost 22 % higher than the base composite through the constitutive equation. This can be attributed to the addition of 15 wt. % HA in the Mg-3Zn matrix, causing the resistance to deformation in the structure. HA has shown traits of an ideal reinforcement to tailor the degradation kinetics of Mg-based temporary orthopedic implants. However, the large difference in the melting temperature of HA and Mg metal leads to an insignificant interaction between them during the sintering process, which has been a significant limitation in their consolidation. Thus, in order to enhance the capability of HA to bond better with the Mg matrix, an attempt was made by co-substitution of Mg2+ and Zn2+ ions with HA, for achieving better bonding between the reinforcement and matrix material. Moreover, such co-substitution increases the similarity of the HA structure to that of natural apatite in human bone. Co-precipitated HA was synthesized through a wet precipitation method, where Mg and Zn ions were successfully incorporated into HA. Spark plasma sintering was used to fabricate the CoHA reinforced Mg-based composites. The 15 wt. % CoHA composite enhanced the ultimate compressive strength by 113%, as compared to the one without CoHA. Further 10 wt. % HA showed a better degradation rate in immersion test. All the CoHA reinforced composites were found to be biocompatible in nature and no toxic effects were observed. In-vitro cytocompatibility results are also encouraging towards its intended application. Collectively, the analysis of the outcomes of this research proposes Mg-HA-based biodegradable structures as a promising candidate in temporary orthopedic implants for fracture fixing accessories. It can bring significant advancement to the functionality of commercially used temporary orthopedic implants by taking care of existing limitations, while inducing inherent capacity for healing bone fractures.