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 ε-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.

通过生物相容性材料实现的基因持续传递代表了一种新颖的策略，可增强骨骼再生，同时提供针对宿主免疫反应的保护。然而，与基于脂质体的载体相比，用于体内有效miRNA递送的多功能可生物降解的生物相容性生物材料的开发仍然是骨再生中的挑战。在这里，我们开发了一种基于支链甘油多肽聚合物（GEPL）的抗菌非病毒载体，作为一种高效的miR-29b递送系统，可调节骨髓干细胞（BMSCs）和体内的成骨分化骨骼再生。与市售聚乙烯亚胺（PEI 25 kD）和Lipofectamine 2000（Lipo 2000）相比，GEPL显示出微不足道的细胞毒性，出色的抗菌活性，良好的miR-29b结合亲和力，miR-29b高效递送到体外BMSCs的成骨分化中。另外，相对于Lipo 2000和ε-聚赖氨酸（EPL），优化的GEPL-miR-29b复合物显着改善了体内的骨组织再生。我们的结果揭示了一种合理设计多功能生物材料的有前途的策略，作为用于组织再生和疾病治疗的高效miRNA传递载体。