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MiRNA320a Inhibitor-Loaded PLGA-PLL-PEG Nanoparticles Contribute to Bone Regeneration in Trauma-Induced Osteonecrosis Model of the Femoral Head

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Tissue Engineering and Regenerative Medicine Aims and scope

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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Data availability statement

The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by National Science Foundation of China (Grant Number 81774348 and 81874477); and Science and Technology Project of Henan Province (Grant number 212102310365).

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Author notes

  1. Ying Zhang and Chuan Li have Contributed equally to this work.

Authors and Affiliations

  1. Medical Center of Hip, Luoyang Orthopedic-Traumatological Hospital (Orthopedics Hospital of Henan Province), No. 82 Qiming South Road, Luoyang, 471002, Henan, China

    Ying Zhang, Leilei Zhang & Xiangyang Cao

  2. Department of Orthopedics, 920Th Hospital of Joint Logistic Support Force, Kunming, 650032, Yunnan, China

    Chuan Li

  3. Institute of Orthopaedics of Guangzhou, University of Traditional Chinese Medicine, Guangzhou, 510240, China

    Qiushi Wei & Wei He

  4. The Third Affiliated Hospital of Guangzhou, University of Traditional Chinese Medicine, Guangzhou, 510240, China

    Qiushi Wei & Wei He

  5. Henan University of Traditional Chinese Medicine, Zhengzhou, 450046, Henan, China

    Qiang Yuan, Yiping Dong & Zhenhao Jing

  6. Hunan University of Traditional Chinese Medicine, Changsha, 410208, Hunan, China

    Ning Zhang

  7. Guangzhou University of Traditional Chinese Medicine, Guangzhou, 510405, Guangdong, China

    Haibin Wang

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  1. Ying Zhang
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Correspondence to Ying Zhang or Xiangyang Cao.

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Ethical statement

All the experimental operations for rabbits was fully in accordance with the Guide for the Care and Use of Laboratory Animals, and this study was approved by the Henan Provincial Hospital orthopaedic ethics committee of Luoyang Orthopaedic Hospital Hospital (Approval no. 2014ZY02094).

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Zhang, Y., Li, C., Wei, Q. et al. MiRNA320a Inhibitor-Loaded PLGA-PLL-PEG Nanoparticles Contribute to Bone Regeneration in Trauma-Induced Osteonecrosis Model of the Femoral Head. Tissue Eng Regen Med 21, 185–197 (2024). https://doi.org/10.1007/s13770-023-00580-7

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