MAGNESIUM BASED BIODEGRADABLE MATERIALS SYSTEM FOR ORTHOPEDIC APPLICATION

Abstract

Bone is the second most transplanted tissue worldwide, with an annual 4 million operations using different alternative bones. Non-degradable metal-based orthopaedic accessories have been widely used over centuries for load-bearing applications in bone fracture or defect healing management due to their excellent mechanical properties. However, these being permanent in nature, needs a re-surgery after the healing of the bone tissue to retract them. Thus, the degradability of materials becomes essential for orthopaedic accessories that support fractured and damaged bones to avoid second surgery for their removal after healing. Magnesium (Mg)-based biodegradable material systems are suitable for this purpose, due to their similar density and elastic modulus with that of native bone, which eventually reduces the stress-shielding effect. The major limitation of Mg metal is its low corrosion resistance in physiological environments, which also reduces its mechanical and physical characteristics in vivo. Fabrication of Mg-based composites facilitates tailoring the degradation and mechanical behaviour of composites by varying the shape, size, composition and distribution of reinforcement phase in the matrix. In this regard, hydroxyapatite (HA) reinforcement in Mg-based composites stands out due to their inherent properties, like, corrosion resistance, osteoconduction and osteoinduction, apart from the compositional similarity with human bones. Thus, the influence of shape and size (cylindrical and round) of bioactive HA was studied by reinforcing it in the Mg-3Zn/HA composite fabricated via spark plasma sintering (SPS). Reinforcement of smaller-size cylindrical HA in the Mg-3Zn matrix reduced the interparticle spacing. It generated comparatively higher constraints to the matrix deformation, which enhanced the hardness and elastic modulus of the cylindrical HA reinforced composite compared to round HA-reinforced composite. Ultimate compressive strength of cylindrical HA reinforced composite enhanced by ~22 and 40%, compared to round HA and Mg-3Zn composites. In addition, the corrosion resistance of cylindrical HA-reinforced composite was significantly improved compared to Mg-3Zn and round HA-reinforced composite due to higher bioactive properties. Then, the different compositions of optimized cylindrical shape HA (0, 2, 5 and 10 wt.%) were used as the reinforcement to fabricate Mg-3Zn/HA composite using a conventional sintering route. Addition of 5 wt.% HA effectively reduces the corrosion rate by 42% and improves the compressive yield strength of biodegradable magnesium alloy by 23%, as compared to Mg-3Zn composite. In-vitro biocompatibility evaluation reveals that the osteoblast cells show better growth and proliferation on HA-reinforced surfaces of the composites.In a quest for a suitable fabrication technique, which could effectively accommodate higher HA composition in the Mg-3Zn matrix, spark plasma sintering (SPS) was explored. Mg-3Zn/HA (0, 5 and 15 wt.%) composites were fabricated via SPS and evaluated in terms of bioactivity and biodegradation behaviour in two different milieus (simulated body fluid (SBF) and fetal bovine serum (FBS)). Incorporating the higher composition of HA into the Mg-3Zn matrix has significantly improved apatite formation after fourteen days of static immersion in SBF. Compared to FBS, SBF is found to be more effective in precipitating apatite on the Mg-3Zn/HA surface. Higher protein adsorption on 15 wt.% HA composite surfaces in FBS solution enhanced the degradation resistance compared to immersion in SBF solution. Further, these composites were also evaluated in terms of bio-tribocorrosion (simultaneous action of mechanical and corrosion stimuli) and in-vivo degradation and osteocompatibility behaviour in the humerus bone of the avian model. Addition of 15 wt.% HA in the Mg-3Zn matrix significantly enhanced the wear resistance in the physiological environment. The degradation rate of the composite increased by ~76% under the condition of tribocorrosion. Moreover, 15 wt.% HA added composite has shown ~55% higher corrosion resistance than composite without HA. X-ray radiograph analysis of the intramedullary inserts showed consistent degradation and positive tissue response progression up to eighteen weeks of implantation. The 15 wt.% HA reinforced composites have shown better bone regeneration properties than other inserts. These studies provide new insight into developing next-generation Mg-3Zn/HA biodegradable composites via spark plasma sintering for temporary fracture fixing accessories (e.g. screws and plates) with excellent biocompatibility. However, the fabrication of large structures of fracture accessories (e.g., intramedullary nails) via the SPS route is challenging due to the limitation of dye-punch size and feasibility. Hence, an attempt was made to carry out the multiaxial hot forging (MAHF) process on Mg-3Zn alloys to study its grain refinement and possible improvement in mechanical, corrosion, and bioactivity behaviour. The yield and ultimate compressive strength of Mg-3Zn alloys are found to increase significantly, after the third cycle of MAHF, potentially due to the grain size refinement. Accelerated corrosion and in-vitro immersion studies (till fourteen days) in SBF showed improvements in corrosion resistance with the refined grain structure after the third cycle of MAHF, due to the increased grain boundary area, which offered more nucleation sites for apatite precipitation. To evaluate the osteocompatibility and in-vivo biodegradation behaviour, the intramedullary nails made of Mg-3Zn alloy were implanted in the intramedullary canal of the femur bone of the dog. Radiological examination of intramedullary nails showed progressive degradation and excellent bone formation ability during a period of sixty days. Apart from fracture fixing management, another major challenge is the healing of defective and diseased bone tissue. An attempt was made to fabricate the biodegradable three-dimensional porous Mg-based scaffolds via conventional and spark plasma sintering methods. The bilayer coating [poly (caprolactone) (PCL) polymer followed by a gelatin-x HA(x=0.5, 1, 1.5 and 2 wt.%) composite layer] on porous Mg-3Zn scaffolds was fabricated to improve the corrosion resistance and bioactivity of the developed scaffold. In the case of SPS, the ultimate compressive strength of the M3Z-PG1.5H scaffold was enhanced by ~69% compared to M3Z (noncoated) scaffolds. During antibacterial testing, a higher inhibition area zone was observed for M3Z-PG1.5H scaffolds compared to other scaffolds. The drug-loaded M3Z-PG1.5H scaffold showed ~50% cumulative drug release in one day. Radiological examination of the M3Z-PG1.5H scaffold implanted in the tibia defect (created in a rat model) has shown progressive degradation and significant bone formation till thirty days. The histopathology images of vital organs (kidney, liver, and heart) showed no toxicity in the body after thirty days. In the case of conventional sintering of Mg-3Zn scaffolds, 30 wt.% of space holder showed better structural integrity and mechanical properties than 40 wt.%. Incorporating 2 wt.% HA in gelatine coating caused peeling off the layer due to the agglomeration and led to the coating breaking during in-vitro testing. Mg-3Zn-PG1H and Mg-3Zn-PG1.5H scaffolds have shown excellent in-vitro biocompatibility compared to other scaffolds. In addition, Mg-3Zn-PG1H and Mg-3Zn-PG1.5H scaffolds have also shown a higher inhibition area during antibacterial testing. These studies provide new insight into developing next-generation Mg-3Zn-based biodegradable porous scaffolds via spark plasma and conventional sintering for healing bone defects. Collectively, the outcome of this research proposes Mg-3Zn/HA-based biodegradable implants and surface-modified biodegradable porous Mg-3Zn scaffolds promising candidates as temporary orthopaedic accessories for bone fracture and defect management. It can significantly advance the Mg-based system by taking care of existing limitations of commercially available implants and scaffolds, while inducing inherent capacity for healing bone defects and fractures.