Engineered Fe(OH)3 nanoparticle-coated and rhBMP-2-releasing PLGA microsphere scaffolds for promoting bone regeneration by facilitating cell homing and osteogenic differentiation

Abstract

Stem cells are an alternative solution for repairing bone defects. Cell migration and homing from the edge of the defect is important for new bone formation. However, the hostile ischemic environment results in limited migration, homing and survival of stem cells. In this article, ferric hydroxide (Fe(OH)₃) nanoparticle-coated poly(lactic-co-glycolic acid) microspheres (FePLGA) were designed via a Pickering emulsion to facilitate stem cell homing. In the process, Fe(OH)₃ nanoparticles were immobilized uniformly on the surface of FePLGA microspheres. The morphology, element analysis and Fe content of the FePLGA microspheres were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and inductively coupled plasma atomic emission spectroscopy (ICP-AES). Then, these microspheres were sintered to form porous microsphere scaffolds. Recombinant human bone morphogenetic protein-2 (rhBMP-2) was immobilized on the scaffolds via a polydopamine coating to induce osteogenic differentiation. The cell viability, adhesion and migration of mouse bone marrow stromal cells (mBMSCs) cultured on different scaffolds were tested. The results indicated that the mBMSC culture on scaffolds containing Fe(OH)₃ nanoparticles exhibited better proliferation, osteoblastic differentiation and migration. Moreover, the iron-containing, rhBMP-2-releasing scaffolds could enhance cell homing efficiency and promote bone formation and osteoconduction when implanted into critical size bone defect models of rabbit femur. Therefore, this new porous PLGA scaffold modified with iron and rhBMP-2 promotes bone repair by recruiting stem cells to the defect site and inside of scaffolds.