3D Hybrid Nanofiber Aerogels Combining with Nanoparticles Made of a Biocleavable and Targeting Polycation and MiR-26a for Bone Repair

The healing of large bone defects represents a clinical challenge, often requiring some form of grafting. 3D nanofiber aerogels could be a promising bone graft due to their biomimetic morphology and controlled porous structures and composition. miR-26a has been reported to induce the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and facilitate bone formation. Introducing miR-26a with a suitable polymeric vector targeting BMSCs could improve and enhance the functions of 3D nanofiber aerogels for bone regeneration. Herein, the comb-shaped polycation (HA–SS–PGEA) is first developed, carrying a targeting component, biocleavable groups, and short ethanolamine (EA)-decorated poly(glycidyl methacrylate) (PGMA) (abbreviated as PGEA) arms as miR-26a delivery vector. Thereafter, the cytotoxicity and transfection efficiency of this polycation and cellular response to miR-26a-incorporated nanoparticles (NPs) are assessed in vitro. HA–SS–PGEA exhibits a stronger ability to transport miR-26a and exert its functions than the gold standard polyethyleneimine (PEI) and low-molecular-weight linear PGEA. The efficacy of HA–SS–PGEA/miR-26a NPs loaded 3D hybrid nanofiber aerogels showing a positive effect on the cranial bone defect healing is finally examined. Together, the combination of 3D nanofiber aerogels and functional NPs consisting of a biodegradable and targeting polycation and therapeutic miRNA could be a promising approach for bone regeneration.