Customized high-throughput microfluidic production of multifunctional porous microspheres for bone repair.

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.