Copper-doped mesoporous hydroxyapatite microspheres synthesized by a microwave-hydrothermal method using creatine phosphate as an organic phosphorus source: application in drug delivery and enhanced bone regeneration
Copper-doped mesoporous hydroxyapatite microspheres synthesized by a microwave-hydrothermal method using creatine phosphate as an organic phosphorus source: application in drug delivery and enhanced bone regeneration
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以磷酸肌酸为有机磷源，微波水热法合成铜掺杂介孔羟基磷灰石微球：在药物输送和增强骨再生中的应用
DOI：
10.1039/c6tb02747d
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发表时间：
2017
影响因子：
7
通讯作者：
He Yaohua
中科院分区：
文献类型：
--
作者：
Yu Weilin;Sun Tuan-Wei;Ding Zhenyu;Qi Chao;Zhao Huakun;Chen Feng;Shi Zhongmin;Zhu Ying-Jie;Chen Daoyun;He Yaohua
具有药物递送能力、促成骨和促血管生成活性的多功能生物材料的开发在再生医学领域引起了越来越多的兴趣。以磷酸肌酸为有机磷源，采用微波-水热法成功合成了具有模拟缺氧功能的铜掺杂介孔羟基磷灰石微球（Cu-MHMs）。制备了掺杂0.2，0.5，1 mol% Cu的Cu-MHM。由HAP纳米棒或纳米片组成的Cu-MHMs表现出分级介孔中空结构和高比表面积。以盐酸阿霉素（DOX）为模型药物，考察了Cu-MHMs作为药物纳米载体的性能。Cu-MHMs具有较高的载药量和pH响应性释药行为。此外，将Cu-MHMs掺入壳聚糖（CS）基质中，以构建用于骨再生的仿生支架。Cu-MHM/CS复合支架保持了较高的孔隙率，并显示出Cu离子的持续释放。更重要的是，Cu-MHM/CS支架不仅增强了大鼠骨髓间充质干细胞（rBMSCs）的成骨分化，而且还促进了EA.hy926细胞的迁移和管形成。当植入大鼠临界大小的颅骨缺损中时，与MHM/CS支架相比，Cu-MHM/CS支架在术后8周显著增强骨再生，伴随着更多的新血管形成。这些结果表明，模拟低氧的Cu-MHM/CS支架能够促进成骨和血管生成，促进骨再生，为血管化组织工程骨的构建奠定了基础。
The development of multifunctional biomaterials with drug delivery ability, and pro-osteogenic and pro-angiogenic activities has garnered increasing interest in the field of regenerative medicine. In the present study, hypoxia-mimicking copper (Cu)-doped mesoporous hydroxyapatite (HAP) microspheres (Cu-MHMs) were successfully synthesized through a microwave-hydrothermal method by using creatine phosphate as an organic phosphorus source. The Cu-MHMs doped with 0.2, 0.5 and 1 mol% Cu were prepared. The Cu-MHMs consisting of HAP nanorods or nanosheets exhibited a hierarchically mesoporous hollow structure and a high specific surface area. Then the Cu-MHMs were investigated as a drug nanocarrier using doxorubicin hydrochloride (DOX) as a model drug. The Cu-MHMs showed a relatively high drug-loading capacity and a pH-responsive drug release behavior. Furthermore, the Cu-MHMs were incorporated into a chitosan (CS) matrix to construct a biomimetic scaffold optimized for bone regeneration. The Cu-MHM/CS composite scaffolds maintained high degrees of porosity and showed a sustained release of Cu ions. More importantly, the Cu-MHM/CS scaffolds not only enhanced the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs) but also promoted the migration and tube formation of EA.hy926 cells. When implanted in rat critical-sized calvarial defects, the Cu-MHM/CS scaffolds significantly enhanced bone regeneration accompanied by more new blood vessel formation at 8 weeks post-operation compared with the MHM/CS scaffolds. These results suggest that the hypoxia-mimicking Cu-MHM/CS scaffolds could encourage bone regeneration by enhancing osteogenesis and angiogenesis simultaneously, which bodes well for the reconstruction of vascularized tissue-engineered bone.