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Injectable bioactive polymethyl methacrylate–hydrogel hybrid bone cement loaded with BMP-2 to improve osteogenesis for percutaneous vertebroplasty and kyphoplasty

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Abstract

Polymethyl methacrylate (PMMA) bone cement is used in augmenting and stabilizing fractured vertebral bodies through percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP). However, applications of PMMA bone cement are limited by the high elasticity modulus of PMMA, its low biodegradability, and its limited ability to regenerate bone. To improve PMMA bioactivity and biodegradability and to modify its elasticity modulus, we mixed PMMA bone cement with oxidized hyaluronic acid and carboxymethyl chitosan in situ cross-linking hydrogel loaded with bone morphogenetic protein-2 (BMP-2) to achieve novel hybrid cement. These fabricated PMMA–hydrogel hybrid cements exhibited lower setting temperatures, a lower elasticity modulus, and better biodegradability and biocompatibility than that of pure PMMA cement, while retaining acceptable setting times, mechanical strength, and injectability. In addition, we detected release of BMP-2 from the PMMA–hydrogel hybrid cements, significantly enhancing in vitro osteogenesis of bone marrow mesenchymal stem cells by up-regulating the gene expression of Runx2, Col1, and OPN. Use of PMMA–hydrogel hybrid cements loaded with BMP-2 on rabbit femoral condyle bone-defect models revealed their biodegradability and enhanced bone formation. Our study demonstrated the favorable mechanical properties, biocompatibility, and biodegradability of fabricated PMMA–hydrogel hybrid cements loaded with BMP-2, as well as their ability to improve osteogenesis, making them a promising material for use in PKP and PVP.

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Acknowledgements

This work was supported by the National Key R&D Program of China (No. 2018YFA0703000), the National Natural Science Foundation of China (Nos. 82071564, 82072412, and 81772326), the Fundamental Research Program Funding of Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (No. JYZZ070), and Project of Shanghai Science and Technology Commission (No. 19XD1434200/18431903700).

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Author notes

  1. Xin Sun and Xin Zhang have contributed equally to this work and are joint first authors.

Authors and Affiliations

  1. Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200001, China

    Xin Sun, Xin Jiao, Jie Ma, Xingzhen Liu, Kangping Shen, Yaokai Gan, Jinwu Wang & Wenjie Jin

  2. School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China

    Xin Zhang, Han Yang & Haiyan Li

  3. Chemical and Environmental Engineering, School of Engineering, RMIT University, 124 La Trobe St., Melbourne, VIC, 3000, Australia

    Haiyan Li

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  1. Xin Sun
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Contributions

JWW, HYL, WJJ, KPS, and YKG were involved in conceptualization; XS, XZ, and WJJ helped in data curation; XS, XZ, and XJ contributed to formal analysis; JWW, WJJ, and XS were involved in funding acquisition; JWW, HYL, and WJJ helped in investigation; XS, XZ, XJ, JM, XZL, and HY contributed to methodology; JWW, HYL, and WJJ were involved in project administration; JWW, HYL, and WJJ helped in supervision; JWW, HYL, and WJJ contributed to validation; XS, XZ, XJ, JM, XZL, and HY were involved in writing—original draft; JWW, HYL, WJJ, KPS, YKG, XS, XZ, and XJ helped in writing—review & editing.

Corresponding authors

Correspondence to Jinwu Wang, Haiyan Li or Wenjie Jin.

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Conflict of interest

The authors declare that there is no conflict of interest.

Ethical approval

All animal procedures and the use of animals in our study were approved by Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine Animal Care and Use Committee and complied with the guidelines of the National Institutes of Health Guide for Care and Use of Laboratory Animals (GB14925-2010).

Availability of data and material

The datasets used or analyzed during the current study are available from the corresponding authors on reasonable request.

Additional information

Jinwu Wang, Haiyan Li, and Wenjie Jin have contributed equally to this work and are joint corresponding authors.

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42242_2021_172_MOESM1_ESM.jpg

Supplemental Fig. S1. Live-Dead staining and quantitative analysis. a Dead cells are depicted in red and living cells in green; b percentage of live cells. (n=3 per group; * p<0.05) (JPG 6858 kb)

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Sun, X., Zhang, X., Jiao, X. et al. Injectable bioactive polymethyl methacrylate–hydrogel hybrid bone cement loaded with BMP-2 to improve osteogenesis for percutaneous vertebroplasty and kyphoplasty. Bio-des. Manuf. 5, 318–332 (2022). https://doi.org/10.1007/s42242-021-00172-1

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