Biodegradable Antibacterial Branched Glycerol-Polypeptide with Efficient in Vitro/in Vitro miRNA-29b Delivery for Promoting Osteogenic Differentiation of Stem Cells and Bone Regeneration

Abstract Sustained gene delivery by biocompatible materials represents a novel strategy for enhancing bone regeneration while providing protection against the damage of host immune response. However, compared with liposome-based vector, development of multifunctional biodegradable biocompatible biomaterials for in vivo efficient miRNA delivery is still a challenge in bone regeneration. Here, we developed an antibacterial non-viral vector based on branched glycerol-polypeptide polymer (GEPL) as a highly efficient miR-29b delivery system to regulate the osteogenic differentiation of bone marrow stem cells (BMSCs) and in vivo bone regeneration. Compared with commercial polyethyleneimine (PEI 25 kD) and Lipofectamine 2000 (Lipo 2000), the GEPL showed negligible cytotoxicity, excellent antibacterial activity, good miR-29b-binding affinity, highly efficient delivery of miR-29b to osteogenic differentiation of BMSCs in vitro. Additionally, relative to the Lipo 2000 and e-polylysine (EPL), optimized GEPL-miR-29b complexes significantly improved the bone tissue regeneration in vivo. Our results reveal a promising strategy for the rational design of multifunctional biomaterials as highly efficient miRNA delivery carriers for tissue regeneration and disease therapy.