Wang Guanyun, Lv Zehui, Wang Tao, Hu Tingting, Bian Yixin, Yang Yu, Liang Ruizheng, Tan Chaoliang, Weng Xisheng
Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.
State Key Laboratory of Chemical Resource Engineering, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, P. R. China.
Adv Sci (Weinh). 2022 Nov 17;10(1):e2204234. doi: 10.1002/advs.202204234.
Although artificial bone repair scaffolds, such as titanium alloy, bioactive glass, and hydroxyapatite (HAp), have been widely used for treatment of large-size bone defects or serious bone destruction, they normally exhibit unsatisfied bone repair efficiency because of their weak osteogenic and angiogenesis performance as well as poor cell crawling and adhesion properties. Herein, the surface functionalization of MgAlEu-layered double hydroxide (MAE-LDH) nanosheets on porous HAp scaffolds is reported as a simple and effective strategy to prepare HAp/MAE-LDH scaffolds for enhanced bone regeneration. The surface functionalization of MAE-LDHs on the porous HAp scaffold can significantly improve its surface roughness, specific surface, and hydrophilicity, thus effectively boosting the cells adhesion and osteogenic differentiation. Importantly, the MAE-LDHs grown on HAp scaffolds enable the sustained release of Mg and Eu ions for efficient bone repair and vascular regeneration. In vitro experiments suggest that the HAp/MAE-LDH scaffold presents much enhanced osteogenesis and angiogenesis properties in comparison with the pristine HAp scaffold. In vivo assays further reveal that the new bone mass and mineral density of HAp/MAE-LDH scaffold increased by 3.18- and 2.21-fold, respectively, than that of pristine HAp scaffold. The transcriptome sequencing analysis reveals that the HAp/MAE-LDH scaffold can activate the Wnt/β-catenin signaling pathway to promote the osteogenic and angiogenic abilities.
尽管人工骨修复支架,如钛合金、生物活性玻璃和羟基磷灰石(HAp),已被广泛用于治疗大面积骨缺损或严重骨破坏,但由于其成骨和血管生成性能较弱以及细胞爬行和粘附性能较差,它们通常表现出不尽人意的骨修复效率。在此,报道了在多孔HAp支架上对MgAlEu层状双氢氧化物(MAE-LDH)纳米片进行表面功能化,作为一种简单有效的策略来制备用于增强骨再生的HAp/MAE-LDH支架。MAE-LDHs在多孔HAp支架上的表面功能化可以显著提高其表面粗糙度、比表面积和亲水性,从而有效地促进细胞粘附和成骨分化。重要的是,在HAp支架上生长的MAE-LDHs能够持续释放Mg和Eu离子,以实现高效的骨修复和血管再生。体外实验表明,与原始HAp支架相比,HAp/MAE-LDH支架具有显著增强的成骨和血管生成特性。体内试验进一步表明,HAp/MAE-LDH支架的新骨量和矿物质密度分别比原始HAp支架增加了3.18倍和2.21倍。转录组测序分析表明,HAp/MAE-LDH支架可以激活Wnt/β-连环蛋白信号通路,以促进成骨和血管生成能力。