Tissue Eng Regen Med.
2024 Jan;21(1):185-197. 10.1007/s13770-023-00580-7.
MiRNA320a Inhibitor-Loaded PLGA-PLL-PEG Nanoparticles Contribute to Bone Regeneration in Trauma-Induced Osteonecrosis Model of the Femoral Head
- Affiliations
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- 1Medical Center of Hip, Luoyang Orthopedic- Traumatological Hospital (Orthopedics Hospital of Henan Province), No. 82 Qiming South Road, Luoyang 471002, Henan, China
- 2Department of Orthopedics, 920Th Hospital of Joint Logistic Support Force, Kunming 650032, Yunnan, China
- 3Institute of Orthopaedics of Guangzhou, University of Traditional Chinese Medicine, Guangzhou 510240, China
- 4The Third Affiliated Hospital of Guangzhou, University of Traditional Chinese Medicine, Guangzhou 510240, China
- 5Henan University of Traditional Chinese Medicine, Zhengzhou 450046, Henan, China
- 6Hunan University of Traditional Chinese Medicine, Changsha 410208, Hunan, China
- 7Guangzhou University of Traditional Chinese Medicine, Guangzhou 510405, Guangdong, China
- KMID: 2550740
- DOI: http://doi.org/10.1007/s13770-023-00580-7
Abstract
- 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.
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