BACKGROUND: This study aimed to explore the effect of a nanomaterial-based miR-320a inhibitor sustained release system in trauma-induced osteonecrosis of the femoral head (TIONFH). METHODS: The miR-320a inhibitor-loaded polyethylene glycol (PEG)- Poly(lactic-co-glycolic acid) (PLGA)- Poly-L-lysine (PLL) nanoparticles were constructed using the double emulsion method. The TIONFH rabbit model was established to observe the effects of miR-320a inhibitor nanoparticles in vivo . Hematoxylin–eosin staining and microcomputed tomography scanning were used for bone morphology analysis. Bone marrow mesenchymal stem cells (BMSCs), derived from TIONFH rabbits, were used for in vitro experiments. Cell viability was determined using the MTT assay. RESULTS: High expression of miR-320a inhibited the osteogenic differentiation capacity of BMSCs in vitro by inhibiting the expression of the osteoblastic differentiation markers ALP and RUNX2. MiR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticles were constructed with a mean loading efficiency of 1.414 ± 0.160%, and a mean encapsulation efficiency of 93.45 ± 1.24%, which released 50% of the loaded miR-320a inhibitor at day 12 and 80% on day 18. Then, inhibitor release entered the plateau. After treatment with the miR-320a inhibitor nanoparticle, the empty lacunae were decreased in the femoral head tissue of TIONFH rabbits, and the osteoblast surface/bone surface (Ob.S/BS), osteoblast number/bone perimeter (Ob.N/B.Pm), bone volume fraction, and bone mineral density increased. Additionally, the expression of osteogenic markers RUNX2 and ALP was significantly elevated in the TIONFH rabbit model. CONCLUSION: The miR-320a inhibitor-loaded PEG-PLGA-PLL nanoparticle sustained drug release system significantly contributed to bone regeneration in the TIONFH rabbit model, which might be a promising strategy for the treatment of TIONFH.
Despite the rapid development of the application of tissue engineering techniques in regenerative bone repair, the repair of severe pathologic bone defects, represented by osteoporotic bone defects, is still a huge challenge. Recent studies have identified local delivery of parathyroid hormone relative peptides (PTHrPs) as a novel pathway for bone repair as well, but how to load and locally release PTHrPs for good bone repair is a major obstacle. Here, a biopolymer of PLGA-PLL loaded with PTHrP1 is electrospunned into nanofiber membranes for guided bone regeneration. In vitro experiments show that PLGA-PLL synergized with PTHrP1 significantly promote osteogenic differentiation and angiogenesis, providing a favorable bone regeneration microenvironment. In vivo experiments show that the membrane recruits endogenous stem cells and promotes their ectopic osteogenic differentiation in an osteoporotic environment. Furthermore, the membrane can promote osteogenic differentiation and angiogenesis in situ and improve the local osteoporotic microenvironment, ultimately promoting the repair of bone defects. Therefore, present study provides a promising strategy for local delivery of PTH, which opens a new pathway for the treatment of osteoporotic bone defects.
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