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使用掺镁多孔羟基磷灰石与重组人骨形态发生蛋白-2联合修复山羊颅骨缺损模型。

Repair of the calvarial defect in goat model using magnesium-doped porous hydroxyapatite combined with recombinant human bone morphogenetic protein-2.

作者信息

Deng Liqing, Li Donghai, Yang Zhouyuan, Xie Xiaowei, Kang Pengde

机构信息

Department of Orthopaedics surgery, West China Hospital, Sichuan University, 37# Wainan Guoxue Road, Chengdu 610041, People's Republic of China. E-mails:

Department of Orthopaedics surgery, Hospital of Chengdu Office of People's Government of Tibetan Autonomous Region, 20# Ximianqiaoheng street, Chengdu 610041, People's Republic of China.

出版信息

Biomed Mater Eng. 2017;28(4):361-377. doi: 10.3233/BME-171678.

Abstract

Hydroxyapatite (HA) is a representative bone repairing biomaterial for its similar composition to human bones and teeth. However, pure HA is limited in application for some unwanted characteristic, such as it is brickle and weakness in degradation. In this study, we modified HA by doping magnesium (Mg) to the material and studied its property in vitro. Besides, we also evaluated the calvarial defect repair effect using MgHA combined with rhBMP-2 in goat model. According to our outcomes, HA composited Mg made the scaffold smooth and the pore regular. In vitro study, Mg could increase the Ca releasing, which may reflect a faster degradation property modified by Mg. And then, MgHA improved the cell viability and proliferation. Furthermore, MgHA could increase the expression of ALP, Collagen I and VEGF protein compared with pure HA (p<0.5, respectively). In the vivo study, MgHA showed a better bone defect healing effect in computed tomography (CT) evaluation compared with HA (p<0.05), but it was inferior to the MgHA/rhBMP-2 (p<0.05). Besides, in the histological analysis, MgHA/rhBMP-2 showed the most effective bone formation outcome (p<0.05), and the MgHA group was significant better than the pure HA group on osteogenesis (p<0.05). Furthermore, Collagen I and VEGF mRNA expression at 12 week in MgHA/rhBMP-2 group were also significat higher than other two groups. In conclusion, Mg had effects on bone formation and angiogenesis, and MgHA/rhBMP-2 had improved the bone defect repair effect. It is worthy of being recommended to bone tissue engineering.

摘要

羟基磷灰石(HA)因其与人骨和牙齿的组成相似,是一种具有代表性的骨修复生物材料。然而,由于一些不理想的特性,如脆性大、降解性差,纯HA的应用受到限制。在本研究中,我们通过向材料中掺杂镁(Mg)对HA进行改性,并研究其体外性能。此外,我们还在山羊模型中评估了MgHA与rhBMP-2联合使用对颅骨缺损的修复效果。根据我们的结果,HA复合Mg后使支架表面光滑且孔隙规则。体外研究表明,Mg可增加钙释放,这可能反映了Mg改性后更快的降解特性。并且,MgHA提高了细胞活力和增殖能力。此外,与纯HA相比,MgHA可增加碱性磷酸酶(ALP)、I型胶原蛋白和血管内皮生长因子(VEGF)蛋白的表达(p均<0.5)。在体内研究中,与HA相比,MgHA在计算机断层扫描(CT)评估中显示出更好的骨缺损愈合效果(p<0.05),但不如MgHA/rhBMP-2(p<0.05)。此外,在组织学分析中,MgHA/rhBMP-2显示出最有效的骨形成结果(p<0.05),且MgHA组在成骨方面明显优于纯HA组(p<0.05)。此外,MgHA/rhBMP-2组在12周时I型胶原蛋白和VEGF mRNA表达也明显高于其他两组。总之,Mg对骨形成和血管生成有影响,MgHA/rhBMP-2改善了骨缺损修复效果。值得推荐用于骨组织工程。

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