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

作　　者：Huanzhong Ji Gang Shen Hanghang Liu Yao Liu Junyu Qian GuoJiang Wan En Luo 

机构地区：[1]State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu,610041,Sichuan,China [2]Institute of Biomedical Engineering,College of Medicine/Key Laboratory of Advanced Technologies of Materials,Ministry of Education,Southwest Jiaotong University,Chengdu,610031,Sichuan,China

出　　处：《Bioactive Materials》2024年第8期422-437,共16页生物活性材料（英文）

基　　金：supported by Grants from the National Natural Science Foundation of China(82370932);Research and Develop Program,West China Hospital of Stomatology Sichuan University(RD-03-202102);Program of Science and Technology Department of Sichuan Province(2023ZYD0107).The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.

摘　　要：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.

关 键 词：Zinc-based biodegradable metals Macrophage Bone regeneration Immune-osteo microenvironment Senile osteoporotic bone fracture healing 

分 类 号：TG146[一般工业技术—材料科学与工程] R68[金属学及工艺—金属材料]