Osteoarthritis (OA) is a degenerative joint disease caused by chronic inflammation that damages articular cartilage. At present, the treatment of OA includes drug therapy to relieve symptoms and joint replacement therapy for advanced OA. However, these palliatives cannot truly block the progression of the disease from the immunological pathogenesis of OA. In recent years, bone marrow mesenchymal stem cell (BMSC) transplantation has shown great potential in tissue engineering repair. In addition, many studies have shown that BMSC paracrine signals play an important role in the treatment of OA through immune regulation and suppressing inflammation. At present, the mechanism of inflammation-induced OA and the use of BMSC transplantation in joint repair have been reviewed, but the mechanism and significance of BMSC paracrine signals in the treatment of OA have not been fully reviewed. Therefore, this article focused on the latest research progress on the paracrine effects of BMSCs in the treatment of OA and the related mechanisms by which BMSCs secrete cytokines to inhibit the inflammatory response, regulate immune balance, and promote cell proliferation and differentiation. In addition, the application potential of BMSC-Exos as a new type of cell-free therapy for OA is described. This review aimed to provide systematic theoretical support for the clinical application of BMSC transplantation in the treatment of OA.
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.
Mg-Sr alloy is considered as a promising biodegradable bone repair material. However, its poor corrosion resistance limits its clinical application. In this study, the corrosion rate of Mg-Sr alloy was greatly improved through the heat treatment. Both in vitro and in vivo corrosion tests (immersion and electrochemical test) showed that corrosion resistance of Mg-Sr alloy was enhanced. In the animal test (New Zealand rabbit), both micro-CT analysis and Van Gieson staining demonstrated that the treated Mg-Sr alloy implant exhibited better osteogenesis and osteointegration ability, which accelerate the healing of bone defect. The results indicate that the treated Mg-Sr alloy has great possibility and potential for application as a new bone repair material.
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.