Osteogenesis-synchronized degradation of Mg⁺-doped calcium sulfate whisker bone grafts for critical-sized bone defect repair.

Abstract

BACKGROUND: Bone defects remain a major clinical challenge in orthopedic and reconstructive surgery. However, conventional inorganic ceramic biomaterials are limited by many problems, such as poor plasticity, limited osteogenic potential, and uncontrolled degradation kinetics, resulting in failing to keep pace with new bones' healing. Harmonizing biomaterial degradation with osteogenesis thus remains a crucial problem to be addressed in bone tissue engineering. METHODS: In this study, Mg-doped calcium sulfate whiskers (MCSW) are synthesized by adopting a high-temperature autoclave method and are fabricated into bone grafting via die-casting molding. Their physicochemical properties, including surface morphology, solution diffusion behavior, mechanical performance, elemental distribution, and Mgrelease kinetics, are systematically characterized. Biocompatibility and in vitro osteoinductive potential are evaluated through assaying cell viability and analyzing osteogenic differentiation. Furthermore, the bone grafting is implanted into critical-sized calvarial defect models in Sprague-Dawley rats, and their bones' regenerative efficacy is assessed by micro-computed tomography (micro-CT) and histological staining. RESULTS: MCSW exhibits many characteristics, including a rough surface, solution-dependent degradation behavior, appropriate mechanical strength, as well as sustained and controlled Mgrelease, presenting favorable physicochemical properties with tunable degradation, which shows it is suitable for applying to bone tissue engineering. In vitro studies demonstrate excellent biocompatibility, supporting the survival, proliferation, and osteogenic differentiation of BMSCs, as proved by enhanced alkaline phosphatase (ALP) activity and calcium mineral deposition. More importantly, the in vivo degradation rate of MCSW is well synchronized with osteogenesis, resulting in effective bone regeneration and satisfactory repair of critical-sized defects. CONCLUSION: This Mg-doping strategy for calcium sulfate whiskers provides a novel and effective approach to enhance osteogenic activity and achieve tunable degradation in bone tissue engineering biomaterials, thereby showing strong potential for future clinical application.