Hu Guangyu, Zeng Shuyun, Shao Tianao, Li Yong, Han Yaoxian, Tu Jiawei, Mao Jiahui, Xiao Yanbin, Zhang Lei
State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.
Department of Orthopaedics, The Third Affiliated Hospital of Kunming Medical University, China.
Biomater Adv. 2025 Dec;177:214426. doi: 10.1016/j.bioadv.2025.214426. Epub 2025 Jul 21.
The development of bone repair materials has become a critical focus in addressing bone defects. Existing methods, such as autografts and allografts, are limited by issues like immune rejection and insufficient local anti-infection. Despite the promise of biocompatible scaffolds in drug and cell delivery, challenges persist in creating uniform, stable and injectable scaffolds with multifunctional properties for effective bone repair. Here, we present a customized coaxial microfluidic system designed for the high-throughput fabrication of PDTH porous microspheres (PDTH PMs). This system ensures precise control over microsphere size and structure, producing uniform, stable microspheres with interconnected pores that significantly enhance drug encapsulation efficiency. The PDTH PMs, composed of PLGA and functionalized with PDA and a hydrogel containing TOB and HA nanoparticles, demonstrate remarkable biocompatibility, ROS scavenging, and antibacterial properties. In vitro, these microspheres effectively promote BMSC proliferation, migration, and osteogenic differentiation. In vivo, using a rat calvarial bone defect model, PDTH PMs show significant improvement in bone regeneration, with increased bone mineral density and new bone formation. Biosafety in vivo assessments via histological examination and blood analysis confirm no adverse effects on major organs. Our work introduces a versatile method for bone defect repair, highlighting the potential of microfluidic-prepared multifunctional microspheres in bone regeneration strategies.
骨修复材料的发展已成为解决骨缺损问题的关键焦点。现有的方法，如自体骨移植和异体骨移植，受到免疫排斥和局部抗感染不足等问题的限制。尽管生物相容性支架在药物和细胞递送方面具有前景，但在制造具有多功能特性的均匀、稳定且可注射的支架以实现有效的骨修复方面仍存在挑战。在此，我们展示了一种定制的同轴微流控系统，该系统专为高通量制备聚多巴胺-四氢巴马汀多孔微球（PDTH PMs）而设计。该系统确保对微球尺寸和结构进行精确控制，生产出具有相互连接孔隙的均匀、稳定的微球，显著提高药物包封效率。由聚乳酸-羟基乙酸共聚物（PLGA）组成并经多巴胺（PDA）功能化以及含有妥布霉素（TOB）和羟基磷灰石（HA）纳米颗粒的水凝胶修饰的PDTH PMs，表现出显著的生物相容性、活性氧清除能力和抗菌性能。在体外，这些微球有效地促进骨髓间充质干细胞（BMSC）的增殖、迁移和成骨分化。在体内，使用大鼠颅骨骨缺损模型，PDTH PMs在骨再生方面显示出显著改善，骨矿物质密度增加且有新骨形成。通过组织学检查和血液分析进行的体内生物安全性评估证实对主要器官无不良影响。我们的工作引入了一种用于骨缺损修复的通用方法，突出了微流控制备的多功能微球在骨再生策略中的潜力。
