Biodegradable Zn-2Cu-0.5Zr alloy promotes the bone repair of senile osteoporotic fractures via the immune-modulation of macrophages

• Published in: Bioactive materials 2024-08, Vol.38, p.422-437
• Main Authors: Ji, Huanzhong, Shen, Gang, Liu, Hanghang, Liu, Yao, Qian, Junyu, Wan, GuoJiang, Luo, En
• Format: Article
• Language: English
• Subjects: Aging; Biocompatibility; Biodegradability; Biodegradable materials; Biomedical materials; Bone biomaterials; Bone healing; Bone imaging; Bone implants; Bone marrow; Bone regeneration; Cytokines; Cytotoxicity; Differentiation (biology); Fractures; Genotype & phenotype; Geriatrics; Healing; Immune system; Immune-osteo microenvironment; Immunomodulation; Injuries; Macrophage; Macrophages; Mechanical properties; Mesenchymal stem cells; Metals; Microenvironments; Modulation; Older people; Orthopaedic implants; Orthopedics; Osteoporosis; Senile osteoporotic bone fracture healing; Stem cells; Surgical implants; System effectiveness; Tensile strength; Titanium alloys; Ultimate tensile strength; Yield stress; Zinc; Zinc base alloys; Zinc-based biodegradable metals
• ISSN: 2452-199X; 2097-1192; 2452-199X
• DOI: 10.1016/j.bioactmat.2024.05.003

Delayed bone-healing of senile osteoporotic fractures remains a clinical challenge due to the alterations caused by aging in bone and immune systems. The novel biomaterials that address the deficiencies in both skeletal cells and immune systems are required to effectively treat the bone injuries of older patients. Zinc (Zn) has shown promise as a biodegradable material for use in orthopedic implants. To address the bone-healing deficiencies in elderly patients with bone injuries, we developed a biodegradable Zn-based alloy (Zn–2Cu-0.5Zr) with enhanced mechanical properties, including a yield strength of 198.7 MPa and ultimate tensile strength of 217.6 MPa, surpassing those of pure Zn and Zn–2Cu alloys. Cytotoxicity tests conducted on bone marrow mesenchymal stem cells (BMSCs) and MC3T3-E1 cells demonstrated that the extracts from Zn–2Cu-0.5Zr alloy exhibited no observable cytotoxic effects. Furthermore, the extracts of Zn–2Cu-0.5Zr alloy exhibited significant anti-inflammatory effects through regulation of inflammation-related cytokine production and modulation of macrophage polarization. The improved immune-osteo microenvironment subsequently contributed to osteogenic differentiation of BMSCs. The potential therapeutic application of Zn–2Cu-0.5Zr in senile osteoporotic fracture was tested using a rat model of age-related osteoporosis. The Zn–2Cu-0.5Zr alloy met the requirements for load-bearing applications and accelerated the healing process in a tibial fracture in aged rats. The imaging and histological analyses showed that it could accelerate the bone-repair process and promote the fracture healing in senile osteoporotic rats. These findings suggest that the novel Zn–2Cu-0.5Zr alloy holds potential for influencing the immunomodulatory function of macrophages and facilitating bone repair in elderly individuals with osteoporosis. [Display omitted] •The novel biodegradable ZnCuZr alloy system exhibits enhanced mechanical properties to meet the requirements of fracture fixation.•The presence of zinc ions from ZnCuZr alloy can exert an anti-inflammatory effect during the transition of macrophages into the M2 phenotype.•The favorable bone immune microenvironment significantly enhances the osteogenic differentiation of bone marrow mesenchymal stem cells through the activation of the Wnt/β-catenin signaling pathway.•The ZnCuZr alloy system expedites the process of bone regeneration and facilitates the healing of osteoporotic fractures in aged rats.