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Bio-Design and Manufacturing  2022 Vol.5 No.2 P.318-332

http://doi.org/10.1007/s42242-021-00172-1


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


Author(s):  Xin Sun, Xin Zhang, Xin Jiao, Jie Ma, Xingzhen Liu, Han Yang, Kangping Shen, Yaokai Gan, Jinwu Wang, Haiyan Li & Wenjie Jin

Affiliation(s):  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; more

Corresponding email(s):   wangjw-team@shsmu.edu.cn, haiyan.li@sjtu.edu.cn, surgeonjin@126.com, sunxinspine@sina.com, zhangxinsjtu@sjtu.edu.cn, jiaoxin2020@126.com, doctorjack@163.com, spine2009@sina.com, yanghan0609@sjtu.edu.cn, shkp2016@163.com, ganyk2004@126.com

Key Words:  Polymethyl methacrylate bone cement, Hydrogel, Bone morphogenetic protein-2, Osteogenesis, Percutaneous vertebroplasty


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Xin Sun, Xin Zhang, Xin Jiao, Jie Ma, Xingzhen Liu, Han Yang, Kangping Shen, Yaokai Gan, Jinwu Wang, Haiyan Li & Wenjie Jin. Injectable bioactive polymethyl methacrylate–hydrogel hybrid bone cement loaded with BMP-2 to improve osteogenesis for percutaneous vertebroplasty and kyphoplasty[J]. Journal of Zhejiang University Science D, 2022, 5(2): 318-332.

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author="Xin Sun, Xin Zhang, Xin Jiao, Jie Ma, Xingzhen Liu, Han Yang, Kangping Shen, Yaokai Gan, Jinwu Wang, Haiyan Li & Wenjie Jin",
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doi="10.1007/s42242-021-00172-1"
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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.

上交九院金文杰、王金武等 | 负载BMP-2的PMMA-水凝胶混合骨水泥促进成骨用于经皮椎体成形术的研究

本研究论文聚焦负载BMP-2的PMMA-水凝胶混合骨水泥促进成骨用于经皮椎体成形术的研究。经皮椎体成形术(PVP)和经皮后凸成形术(PKP)中应用聚甲基丙烯酸甲酯(PMMA)骨水泥可显著增强并稳定骨折的椎体,是目前治疗骨质疏松性椎体压缩骨折的普遍策略。然而,PMMA骨水泥的弹性模量及固化温度较高,缺乏生物活性并难以降解,限制了其临床应用。本研究将PMMA骨水泥与负载BMP-2的氧化透明质酸和羧甲基壳聚糖自交联水凝胶混合,制备了新型骨水泥。与纯PMMA相比,PMMA-水凝胶混合水泥具有较低的弹性模量和固化温度、较好的生物降解性和生物相容性。同时,该混合骨水泥可以注射使用,能够满足必要的固化时间和力学强度。此外,PMMA-水凝胶混合骨水泥释放的BMP-2,通过上调Runx2、Col1和OPN的表达,增强骨髓间充质干细胞的体外成骨能力。体内实验证明,混合骨水泥可促进兔股骨髁骨缺损中新生骨的生成。综上所述,负载BMP-2的PMMA-水凝胶混合骨水泥为PVP和PKP治疗骨松椎体骨折提供了新思路,具有一定的临床应用前景。

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