Xiuzhi Zhang

Continuous advancements in medical technology and biomaterials have underscored the significant advantages of biodegradable implant materials for bone repair and remodelling over traditional inert metallic implants. Notably, biodegradable magnesium-based materials have gained much attention because of their optimal corrosion rates. Importantly, extensive clinical experience has resulted in the use of biodegradable magnesium-based orthopaedic implants. Both preclinical and clinical studies have consistently demonstrated that Mg has an excellent ability to promote bone tissue formation, a process that is closely associated with the release of Mg2+ and other degradation byproducts. Bone metabolism depends on a dynamic balance of bone formation and bone resorption. Mg2+ has been shown to increase osteoblast (OB) activity while suppressing osteoclast (OC) formation, thus playing a crucial role in bone remodelling and regeneration. In terms of osteolysis inhibition, Mg2+ plays a multifaceted role. First, Mg2+ inhibits OC formation by modulating the activity of mature OCs, their migratory behaviour and the activity of precursor cells. Second, Mg2+ influences OC production by regulating the expression of osteoprotegerin (OPG), receptor activator of nuclear factor kappa-Β ligand (RANKL) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Additionally, Mg2+ impacts bone resorption by altering the immune microenvironment and the levels of hormones and peptides within the body. Furthermore, the alkaline environment generated around the biodegradable magnesium implant and its degradation products (e.g. H2) also significantly inhibit OC formation. Recent research on magnesium-based implants has focused predominantly on their osteogenic properties, with few systematic reviews addressing the mechanisms through which biodegradable magnesium alloys suppress osteoclastic activity. This article summarizes the latest clinical research progress concerning biodegradable magnesium implant materials and their significant regulatory effects and discusses recent advances in the understanding of the regulatory mechanisms of action Mg-based biomaterials on OCs, with the aim of providing a more theoretical basis for the clinical application of biodegradable magnesium-based implants.

Osteoarthritis (OA) is a degenerative joint disease caused by chronic inflammation that damages articular cartilage. In addition to the wear and tear of joints, aberrant remodelling driven by a significant presence of inflammatory mediators within the joint is one of the key mechanisms in the pathogenesis of OA. Among these factors, hyperactivation of Teffs subsets plays a crucial role in promoting this pathological process. The immune imbalance between proinflammatory CD4⁺ effector T cells (proinflammatory Teffs) and Tregs could be a crucial factor in the pathogenesis of OA. Therefore, correcting the imbalance of Tregs/proinflammatory Teffs may slow or inhibit the occurrence and development of OA, which could be a potential target for the treatment of OA. Mesenchymal stem cells (MSCs) possess anti-inflammatory and immunomodulatory properties, regulating both adaptive and innate immunity through mechanisms involving soluble factors such as IDO, PGE2, and TGF-β, as well as cell-to-cell contact and exosomes. Correcting the imbalance between Tregs and proinflammatory Teffs may be one of the mechanisms of MSCs in the treatment of OA. Therefore, this review aims to summarize the relationship between OA and the immune imbalance between Tregs and proinflammatory Teffs, the immunoregulatory role of Tregs in OA, and the role of MSCs and their exosomes in correcting the imbalance between Tregs and proinflammatory Teffs.

The enhancement of osteogenesis and angiogenesis remains a great challenge for the successful regeneration of engineered tissue. Biodegradable Mg and Zn alloys have received increasing interest as potential biodegradable metallic materials, partially due to the biological functions of Mg²⁺ and Zn²⁺ with regard to osteogenesis and angiogenesis, respectively. In the present study, novel biodegradable Zn–xMg (x = 0.2, 0.5, 1.0 wt.%) alloys were designed and fabricated, and the effects of adding different amounts of Mg to the Zn matrix were investigated. The osteogenesis and angiogenesis beneficial effects of Zn²⁺ and Mg²⁺ release during the biodegradation were characterized, demonstrating coordination with the bone regeneration process in a dose-dependent manner. The results show that increased Mg content leads to a higher amount of released Mg²⁺ while decreasing the Zn²⁺ concentration in the extract. The osteogenesis of pre-osteoblasts was promoted in Zn–0.5Mg and Zn–1Mg due to the higher concentration of Mg²⁺. Moreover, pure Zn extract presented the highest activity in angiogenesis, owing to the highest concentration of Zn²⁺ release (6.415 μg/mL); the proliferation of osteoblast cells was, however, inhibited under such a high Zn²⁺ concentration. Although the concentration of Zn ion was decreased in Zn–0.5Mg and Zn–1Mg compared with pure Zn, the angiogenesis was not influenced when the concentration of Mg in the extract was sufficiently increased. Hence, Mg²⁺ and Zn²⁺ in Zn–Mg alloys show a dual modulation effect. The Zn–0.5Mg alloy was indicated to be a promising implant candidate due to demonstrating the appropriate activity in regulating osteogenesis and angiogenesis. The present work evaluates the effect of the Mg content in Zn-based alloys on biological activities, and the results provide guidance regarding the Zn–Mg composition in designs for orthopedic application.