Spontaneous immunomodulation and regulation of angiogenesis and osteogenesis by Sr/Cu-borosilicate glass (BSG) bone cement to repair critical bone defects.

Spontaneous immunomodulation and regulation of angiogenesis and osteogenesis by Sr/Cu-borosilicate glass (BSG) bone cement to repair critical bone defects.
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Sr/Cu-硼硅酸盐玻璃(BSG)骨水泥的自发免疫调节以及血管生成和骨生成的调节修复关键骨缺损

DOI:
10.1016/j.bioactmat.2022.10.021
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发表时间:
2023-05
影响因子:
18.9
通讯作者:
Pan, Haobo
Pan, Haobo
中科院分区:
工程技术1区
文献类型:
--
作者:
Li, Shuaijie;Zhang, Liyan;Liu, Chunyu;Kim, Jua;Su, Kun;Chen, Tingli;Zhao, Limin;Lu, Xiaomei;Zhang, Hao;Cui, Yinglin;Cui, Xu;Yuan, Feng;Pan, Haobo

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像骨水泥这样的可注射骨生物材料的设计和制造应该符合一定的生物学标准,包括:1)巨噬细胞从M1(促炎)表型向M2(抗炎)表型的募集和极化;2)促进血管形成;3)激活骨髓来源干细胞的成骨分化以促进骨愈合。到目前为止,还没有一种可注射的生物材料可以自发地调节涉及炎症、血管生成和成骨的整个骨愈合过程。因此,在本研究中,我们在壳聚糖液相中设计了锶和含铜硼硅酸盐玻璃组成的骨水泥(锶/铜-BSG)来调节骨愈合。体外研究表明,锶和铜离子的控释作用3天后,巨噬细胞抗炎基因IL-1ra和转化生长因子-β1上调,促炎基因IL-1β和IL-6下调。5天时,锶、铜离子可促进血管生成基因(VEGF、bFGF)的表达;7、14、21天时,细胞内的成骨基因(RUNX-2、OCN、OPN)表达增强。5Sr3Cu-BSG骨水泥在不同锶铜比的骨水泥组中抗炎、血管生成和成骨性能最好。短期和长期植入锶/铜-BSG修复大鼠和兔股骨髁骨缺损的实验结果证实了体外实验结果,其中锶/铜-BSG的降解率与骨愈合速度相吻合。与体外相似,5Sr3Cu-BSG组在体内也显示出最高的成骨能力。良好的物理和化学性能以及骨修复能力使锶/铜-BSG骨水泥成为治疗骨缺损的良好生物材料。确定了锶/铜-BSG水泥的凝结机理。锶/铜-BSG骨水泥可调节免疫、血管生成和成骨,从而促进体内和体外骨缺损的修复。锶/铜-BSG骨水泥具有优良的物理化学性能、生物相容性和骨修复能力。
Injectable bone biomaterials like bone cement should be designed and fabricated with certain biological criteria, which include: 1) recruitment and polarization of the macrophages from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype, 2) enhance vascularization, and 3) activate osteogenic differentiation of bone marrow-derived stem cells to promote bone healing. So far, no injectable biomaterials could spontaneously regulate the entire bone healing process that involves inflammation, angiogenesis, and osteogenesis. Therefore, in this study, we designed bone cement comprised of strontium and copper-incorporated borosilicate glass (Sr/Cu-BSG) in the liquid phase of chitosan to modulate bone healing. In vitro studies showed that the controlled release of Sr and Cu ions up-regulated anti-inflammatory genes(IL-1Ra and TGF-β1) while down-regulating pro-inflammatory genes(IL-1β and IL-6) in macrophages at 3 days. Sr and Cu ions also increased the expressions of angiogenic genes (VEGF and bFGF) in HUVECs at 5 days and osteogenic genes (Runx-2, OCN, and OPN) in hBMSCs at 7, 14, and 21 days. 5Sr3Cu-BSG bone cement exhibited the best anti-inflammatory, angiogenic, and osteogenic properties among the bone cement groups with different Sr and Cu ratios. Short-term and long-term implantation of Sr/Cu-BSGs in femoral condylar bone defects of rats and rabbits confirmed the in vitro results, where the degradation rate of Sr/Cu-BSG matched the bone healing rate. Similar to in vitro, the 5Sr3Cu-BSG group also showed the highest bone formation in vivo. Excellent physical and chemical properties, along with its bone repairing ability, make the Sr/Cu-BSG bone cement a good candidate biomaterial for treating bone defects. The setting mechanism of Sr/Cu-BSG cement is ascertained. Sr/Cu-BSG cement modulates immunity, angiogenesis, and osteogenesis to facilitate bone defect repair in vitro and in vivo. Sr/Cu-BSG cement has excellent physical and chemical properties, biocompatibility, and bone repairing ability.
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