Abstract：
Biodegradable polymer microspheres in bone tissue engineering have become appealing as their non-invasive advantages in irregular damage bone repair. However, current microspheres used in BTE still lack sufficient osteogenic capacity to induce effective bone regeneration. In this study, we developed osteogenic composite microspheres concurrently loaded with magnesium oxide (MgO) and zinc oxide (ZnO), both of which are osteogenic active substances, using a facile and scalable emulsification method. The osteogenic composite microspheres exhibited a sequential yet complementary release profile characterized by a rapid release of Mg2+ and a gradual release of Zn2+ in a physiological environment, thereby maintaining the concentration of bioactive ions at a sustained high level. As a result, the combination of Mg2+ and Zn2+ in the composite microspheres led to a synergistic enhancement in biomimetic mineralization and the upregulation in the expression of osteogenic-related genes and proteins at the cellular level. Through a critical-sized calvarial rate defect model, the osteogenic composite microspheres were demonstrated to have strong osteogenic ability to promote new bone formation via ultrasonic imaging, histological and immunohistochemical evaluations. In sum, these osteogenic composite microspheres as microcarriers of Mg2+ and Zn2+ have great potential in the delivery of therapeutic ions for treating bone defects.
摘要：
可生物降解的聚合物微球在骨组织工程中作为其在不规则损伤骨修复中的非侵入性优势而变得吸引人。然而,目前用于BTE的微球仍然缺乏足够的成骨能力来诱导有效的骨再生。在这项研究中,我们开发了同时负载氧化镁（MgO）和氧化锌（ZnO）的成骨复合微球，两者都是成骨活性物质，使用一种容易和可扩展的乳化方法。成骨复合微球表现出连续但互补的释放曲线，其特征是在生理环境中迅速释放Mg2和逐渐释放Zn2。从而将生物活性离子的浓度保持在持续的高水平。因此,复合微球中Mg2和Zn2的结合导致仿生矿化的协同增强以及成骨相关基因和蛋白质在细胞水平上的表达上调。通过临界大小的颅骨率缺陷模型，超声成像显示成骨复合微球具有较强的成骨能力，可促进新骨形成，组织学和免疫组织化学评估。总之,这些成骨复合微球作为Mg2+和Zn2+的微载体，在递送治疗性离子治疗骨缺损方面具有巨大的潜力。
