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Biocompatibility and bone regeneration of PEO/Mg-Al LDH-coated pure Mg: an in vitro and in vivo study

PEO/Mg-Al LDH涂层增强金属镁的生物相容性和成骨作用: 体内外研究

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Abstract

Forming a stable anti-corrosion surface layer on magnesium (Mg) and its alloys has become a major challenge in developing a desirable degradable medical implant in bone. In this study, a porous MgO layer was first formed on Mg by plasma electrolytic oxidation (PEO), and then a Mg-Al layered double hydroxide (LDH) layer was prepared to seal the porous structure of the PEO layer (LDH-2h and LDH-12h) via hydrothermal treatment. The bilayer structure composite coating, which can effectively resist the penetration of surrounding media, is similar to plain Chinese tiles. The in vitro results revealed that compared with other coatings, the LDH-12h composite coating can reduce the release of Mg ions and induce a milder change in pH when immersed in phosphate-buffered saline (PBS). In vitro rat bone marrow stem cell (rBMSC) culture suggested that the LDH-12h composite coating is favorable for cell activity, proliferation and could improve the osteogenic activity of rBMSCs. A subcutaneous implantation test revealed that the as-prepared sample showed enhanced corrosion resistance and histocompatibility in vivo, especially in the LDH-12h group. Moreover, LDH-12h had the lowest rate of degradation and the closest combination with the new bone after being inserted into a rat femur for 12 weeks with no major organ dysfunction. In summary, the asprepared PEO/Mg-Al LDH composite coating is able to improve the corrosion resistance and biocompatibility of Mg and to enhance osteogenic activity in vivo, suggesting its promising prospects for orthopedic applications.

摘要

镁(Mg)及其合金因具有生物可降解和促成骨效应而成为理想的骨内固定材料, 但其抗腐蚀能力差、 体内降解快的缺点限制了其临床应用. 开发稳定的防腐涂层是镁基金属临床应用的主要挑战. 本研究首先通过等离子体电解氧化法(PEO)在Mg表面形成多孔的PEO涂层, 然后通过水热处理制备Mg-Al层状双氢氧化物(LDH)层来封闭MgO层的多孔结构(根据处理时间不同分为LDH-2h和LDH-12h组). 体外实验结果表明, 与其他涂层相比, LDH-12h 组在磷酸盐缓冲液(PBS)中可以有效减少Mg2+释放并抑制pH值变化. 另外, LDH-12h组促进了大鼠骨髓干细胞(rBMSC)的生物活性、 增殖速率以及成骨活性. 大鼠皮下植入试验表明, 经过改性的纯镁金属在体内的耐蚀性和组织相容性增加, 尤其是LDH-12h组. 此外, LDH-12h组植入大鼠股骨12周后降解率最低、 与新生骨结合最紧密, 并且未发现主要器官功能障碍. 本研究所制备的PEO/Mg-Al LDH复合涂层能够明显改善Mg的耐蚀性和生物相容性, 增强体内成骨活性, 具有良好的临床应用前景.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81901048, 81921002, 81620108006 and 31771044), Shanghai Committee of Science and Technology, China (18410760600), and the International Partnership Program of Chinese Academy of Sciences (GJHZ1850).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Prosthodontics, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China

    Jie Wang  (王洁), Xiaolin Wu  (吴晓琳), Ao Zheng  (郑奥), Lingyan Cao  (曹玲燕), Chunhua Yu  (郁春华) & Xinquan Jiang  (蒋欣泉)

  2. State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, China

    Feng Peng  (彭峰), Donghui Wang  (王东辉) & Xuanyong Liu  (刘宣勇)

  3. Department of Orthopedics, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China

    Feng Peng  (彭峰)

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  1. Jie Wang  (王洁)
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Contributions

Author contributions Jiang X, Liu X and Wang J conceived the concept of the study and provided funding support; Peng F and Wang D provided experimental materials and processing technology support; Peng F conducted the part of sample preparation and characterization experiments; Peng F and Wu X conducted the part of in vitro rBMSC experiments; Zheng A, Cao L, Yu C and Wang J conducted the in vivo experiments; Wang J and Peng F performed data analysis and drafted the manuscript; Jiang X, Liu X and Cao L reviewed the manuscript; Wang J, Jiang X, Peng F and Liu X integrated the suggestions of all authors and finished the paper.

Corresponding authors

Correspondence to Xuanyong Liu  (刘宣勇) or Xinquan Jiang  (蒋欣泉).

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Conflict of interest The authors declare that they have no conflict of interest.

Additional information

Jie Wang received her master degree of seven-year program in stomatology from Nanjing University in 2014 and PhD degree from Shanghai Jiao Tong University School of Medicine in 2017. Her research interests include tissue engineering and regenerative medicine, with a particular focus on the biodegradable materials.

Feng Peng received his bachelor degree from Central South University in 2014 and PhD degree from Shanghai Institute of Ceramics, Chinese Academy of Sciences in 2019. His current research interest focuses on biodegradable magnesium alloys for biomedical application.

Xuanyong Liu received his PhD degree in materials science and engineering from Shanghai Institute of Ceramics, Chinese Academy of Sciences, in 2002. His research interests lie in the following areas: nanosized and functionalized surface of biomedical Ti alloys, PEEK and biodegradable magnesium alloys, surface modification of biomaterials using plasma immersion ion implantation & deposition (PIII&D) technology, and plasma sprayed bioactive ceramic coatings.

Xinquan Jiang now serves as the Executive Dean of the College of Stomatology, Shanghai Jiao Tong University, Director of the Department of Prosthodontics of Shanghai Ninth People’s Hospital, Director of Shanghai Engineering and Research Center in the Universities for Advanced Dental Technology and Materials. His lab focuses on the research and application of the regeneration and repair of oral and maxillofacial bone tissues as well as expanding basic research into clinical practice.

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Wang, J., Peng, F., Wu, X. et al. Biocompatibility and bone regeneration of PEO/Mg-Al LDH-coated pure Mg: an in vitro and in vivo study. Sci. China Mater. 64, 460–473 (2021). https://doi.org/10.1007/s40843-020-1392-5

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