Bioresorbable magnesium-based alloys containing strontium doped nanohydroxyapatite promotes bone healing in critical sized bone defect in rat femur shaft

Abstract

Magnesium-based biomaterials have been in extensive research for orthopedic applications for decades due to their optimal mechanical features and osteopromotive nature; nevertheless, rapid degradation restricts their clinical applicability. In this study, pristine magnesium was purified (P-Mg) using a melt self-purification approach and reinforced using indigenously synthesized nanohydroxyapatite (HAP, 0.6 wt.%) and strontium substituted nanohydroxyapatite (SrHAP, 0.6 wt.%) using a low-cost stir assisted squeeze casting method to control their degradation rate. Using electron back-scattered diffraction (EBSD) and X-ray diffraction (XRD) examinations, all casted materials were carefully evaluated for microstructure and phase analysis. Mechanical characteristics, in vitro degradation, and in vitro biocompatibility with murine pre-osteoblasts were also tested on the fabricated alloys. For in vivo examination of bone formation, osteointegration, and degradation rate, the magnesium-based alloys were fabricated as small cylindrical pins with a diameter of 2.7 mm and a height of 2 mm. The pins were implanted in a critical-sized defect in a rat femur shaft (2.7 mm diameter and 2 mm depth) for 8 weeks and evaluated by micro-CT and histological evaluation for bone growth and osteointegration. When compared to P-Mg and P-MgHAP, micro-CT and histological analyses revealed that the P-MgSrHAP group had the highest bone formation towards the periphery of the implant and hence maximum osteointegration. When the removed pins from the bone defect were analyzed using GIXRD, they displayed hydroxyapatite peaks that were consistent with bio-integration. For P-Mg, P-MgHAP, and P-MgSrHAP 8 weeks after implantation , in vivo degradation rates derived from micro-CT were around 0.6 mm/year, 0.5 mm/year, and 0.1 mm/year, respectively. Finally, P-MgSrHAP possesses the requisite degradation rate as well as sufficient mechanical and biological properties, indicating that it has the potential to be used in the development/fabrication of biodegradable bioactive orthopaedic implants.