Magnesium as an emerging bioactive material for orthopedic applications: bedside needs lead the way from innovation to clinical translation.

With the rapid increase in population aging, the number of surgical operations in orthopedics is expected to increase. The gap between the materials applied in clinical orthopedics and materials in discovery and research is obvious due to regulatory requirements for biosafety and treatment efficacy. For the bedside needs, it is important to overcome hurdles by achieving impactful innovation and clinical translation of orthopedic materials. Magnesium (Mg), as an emerging bioactive material, is one of the vital components of the human body and mainly stored in the musculoskeletal system as either a matrix component or an intracellular element for the homeostasis of various physiological functions. However, the degradation and biomechanical performance limit the applications of Mg. This review aims to explore the current challenges and future directions of Mg for clinical translation and provide an update on biomaterials used in orthopedics, factors driving orthopedic innovation, physiology of magnesium ions (Mg²⁺) and its potential clinical applications. To achieve orthopedic application, modification of the performance of Mg as implantable metals and function of the degradation products of Mg in vivo are described. For the clinical needs of treating the steroid-associated osteonecrosis (SAON), Mg screws and Mg-based composite porous scaffolds (Mg/PLGA/TCP: magnesium/poly(lactic-co-glycolic acid) (PLGA)/tricalcium phosphate (TCP)) have been developed, but the challenges of Mg-based implants in load-bearing skeletal sites still exist. To utilize the beneficial biological effects of Mg degradation and overcome the weakness in mechanical stability for fracture fixation, the concept of developing Mg/titanium (Ti) hybrid orthopedic implants is reported, where the Ti component provides effective mechanical support while the inclusion of Mg component potentially optimizes the biomechanical properties of Ti component and facilitate bone healing. This review provides a reference frame for the translation of novel materials and promotes the development of innovative orthopedic biomaterials for clinical applications.