Magnesium-pretreated periosteum for promoting bone-tendon healing after anterior cruciate ligament reconstruction

Magnesium-pretreated periosteum for promoting bone-tendon healing after anterior cruciate ligament reconstruction
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镁预处理骨膜促进前十字韧带重建后骨腱愈合

DOI:
10.1016/j.biomaterials.2020.120576
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发表时间:
2021-01-01
期刊:
影响因子:
14
通讯作者:
Qin,Ling
Qin,Ling
中科院分区:
工程技术1区
文献类型:
--
作者:
Wang,Jiali;Xu,Jiankun;Qin,Ling

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在动物研究和临床试验中,骨膜用于包裹肌腱移植物可以促进肌腱-骨愈合。由于镁离子可显著提高骨膜源性干细胞成骨分化相关细胞因子的水平,因此镁预处理的骨膜可能是用于包裹肌腱移植物的创新方法。为了验证这一假设,我们比较了Mg预处理的骨膜(M-P)和不锈钢(SS)预处理的骨膜(SS-P)在ACL重建中的作用。我们首先发现,从Mg植入物释放的Mg离子部分积累在骨膜中,导致与SS-P相比,M-P中的Mg/Ca比更高。此外,由于组织蛋白酶K(CTSK)的降低,M-P显示出比SS-P显著更高的降钙素基因相关肽(CGRP)和骨膜蛋白表达水平。降钙素基因相关肽和骨膜蛋白的升高有利于骨膜源性干细胞的成骨分化。更重要的是,我们证明了M-P显著增加了骨膜和肌腱之间界面处纤维软骨的形成。总的来说,与SS-P组相比,M-P组表现出显著防止隧道周围骨丢失、更多骨长入肌腱移植物和更高的最大失效载荷。总之,我们的研究需要进一步研究,以转化当前的概念验证结果,优化CGRP、骨膜蛋白和细胞的递送,作为增强ACL重建患者肌腱-骨界面愈合的新型实用治疗策略。
Periosteum can improve tendon-bone healing when applied to wrap the tendon graft in both animal studies and clinical trials. As magnesium (Mg) ions can significantly elevate the levels of relevant cytokines involving in the osteogenic differentiation of periosteum-derived stem cells, the Mg-pretreated periosteum may be an innovative approach for enveloping the tendon graft. To test this hypothesis, we compared the effects of Mg-pretreated periosteum (M − P) and the stainless steel (SS)-pretreated periosteum (SS–P) in ACL reconstruction. We firstly found that the released Mg ions from the Mg implants were partially accumulated in periosteum, resulting in higher Mg/Ca ratio in the M − P compared to the SS-P. Additionally, the M − P showed significantly higher expression levels of calcitonin gene-related peptide (CGRP) and periostin than the SS-P due to the decrease in Cathepsin K (CTSK). Elevation of CGRP and periostin was beneficial for the osteogenic differentiation of periosteum-derived stem cells. More importantly, we demonstrated that the M − P remarkably increased the formation of fibrocartilage at the interface between the periosteum and tendon. Collectively, M − P group demonstrated significantly prevented peri-tunnel bone loss, more osseous ingrowth into the tendon graft and higher maximum load to failure as compared to the SS-P group. In summary, our study warrants further investigations for translating the current proof-of-concept findings to optimize the delivery of CGRP, periostin, and cells as novel practical therapeutic strategy for enhancing tendon-bone interface healing in patients undergoing ACL reconstruction.