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.

在动物研究和临床试验中，将骨膜用于包裹腱移植物都可以改善腱骨愈合。由于镁（Mg）离子可以显着提高涉及骨膜来源干细胞成骨分化的相关细胞因子的水平，因此，用Mg预处理过的骨膜可能是包裹腱移植物的一种创新方法。为了验证该假设，我们比较了经过Mg预处理的骨膜（MP）和经不锈钢（SS）预处理的骨膜（SS–P）在ACL重建中的效果。我们首先发现，从Mg植入物中释放的Mg离子部分聚集在骨膜中，与SS-P相比，导致M-P中的Mg / Ca比更高。另外，由于组织蛋白酶K（CTSK）的降低，MP显示降钙素基因相关肽（CGRP）和骨膜素的表达水平明显高于SS-P。CGRP和骨膜素的升高有利于骨膜来源干细胞的成骨分化。更重要的是，我们证明了M-P显着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，MP组显示出显着防止了隧道周骨丢失，更多的骨向腱移植内生长以及更高的最大破坏负荷。总而言之，我们的研究值得进一步研究，以翻译当前的概念验证结果，以优化CGRP，骨膜素，