The Sr-HA-Loaded PLGA Cage Structure Combines Cells to Construct a Bone Tissue Repair Unit

Abstract Osteoporosis arises from an imbalance where bone resorption outpaces formation, reducing bone mass and mineral density while elevating fracture risk. Subsequent surgical repair of these fractures in compromised bone is prone to cause secondary injury, further increasing the challenges of recovery. In this study, we developed an injectable bone repair unit based on multicellular delivery microspheres, designed to promote the repair of osteoporotic bone defects through the synergistic effect of cells and metal ions. First, cage-structured PLGA microspheres (PLGA-CAS) were fabricated via double-emulsion technique. Subsequently, the surfaces of the PLGA-CAS were uniformly coated with needle-like strontium-doped hydroxyapatite (Sr-HA) particles synthesized by wet-chemical precipitation to form Sr-HA-coated PLGA-CAS (SrHP). Finally, mouse pre-osteoblasts (MC3T3-E1) and human umbilical vein endothelial cells (HUVECs) were separately cultured on the SrHP microspheres, which together constituted the final bone repair unit. Structural and compositional analyses revealed that the PLGA-CAS scaffold possessed an interconnected porous structure with successfully anchored Sr-HA particles. Both SrHP loaded with MC3T3-E1 (M-SrHP) and with HUVECs (H-SrHP) exhibited high cell viability and injectability. Notably, the blended microspheres system incorporating both M-SrHP and H-SrHP (MH-SrHP) simultaneously facilitated osteogenic differentiation, promoted angiogenesis, and inhibited osteoclast differentiation in vitro. This multifunctional construct offers a streamlined platform for osteoporotic bone repair and represents a promising therapeutic strategy for clinical translation.