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双膦酸盐预处理对新鲜异体骨软骨移植的影响:体外移植结构及体内骨整合分析

Effect of Bisphosphonate Pretreatment on Fresh Osteochondral Allografts: Analysis of In Vitro Graft Structure and In Vivo Osseous Incorporation.

作者信息

Moore Drew D, Baker Kevin C, Baker Erin A, Fleischer Mackenzie M, Newton Michael D, Barreras Nicholas, Vaupel Zachary M, Fortin Paul T

出版信息

Orthopedics. 2018 May 1;41(3):e376-e382. doi: 10.3928/01477447-20180320-04. Epub 2018 Mar 26.

DOI:10.3928/01477447-20180320-04
PMID:29570765
Abstract

Fresh allograft transplantation of osteochondral defects restores functional articular cartilage and subchondral bone; however, rapid loss of chondrocyte viability during storage and osteoclast-mediated bone resorption at the graft-host interface after transplantation negatively impact outcomes. The authors present a pilot study evaluating the in vitro and in vivo impact of augmenting storage media with bisphosphonates. Forty cylindrical osteochondral cores were harvested from femoral condyles of human cadaveric specimens and immersed in either standard storage media or storage media supplemented with nitrogenated or non-nitrogenated bisphosphonates. Maintenance of graft structure and chondrocyte viability were assessed at 3 time points. A miniature swine trochlear defect model was used to evaluate the influence of bisphosphonate-augmented storage media on in vivo incorporation of fresh osteochondral tissue, which was quantified via μCT and decalcified histology. In the in vitro study, Safranin-O/Fast Green staining showed that both low- and high-dose nitrogenated-treated grafts retained chondrocyte viability and cartilage matrix for up to 43 days of storage. Allografts stored in nitrogenated-augmented storage media showed both μCT and histologic evidence of enhanced in vivo bony and cartilaginous incorporation in the miniature swine trochlear defect model. Several preclinical studies have shown the potential for enhanced storage of fresh osteochondral allografts via additions of relatively common drugs and biomolecules. This study showed that supplementing standard storage media with nitrogenated bisphosphonates may improve maintenance of chondrocyte viability and graft structure during cold storage as well as enhance in vivo osseous and cartilaginous incorporation of the graft. [Orthopedics: 2018; 41(3):e376-e382.].

摘要

新鲜同种异体骨软骨缺损移植可恢复功能性关节软骨和软骨下骨;然而,储存期间软骨细胞活力的快速丧失以及移植后移植物-宿主界面处破骨细胞介导的骨吸收对结果产生负面影响。作者开展了一项前瞻性研究,评估用双膦酸盐增强储存培养基的体外和体内影响。从人类尸体标本的股骨髁采集40个圆柱形骨软骨芯,并将其浸入标准储存培养基或补充有含氮或不含氮双膦酸盐的储存培养基中。在3个时间点评估移植物结构和软骨细胞活力的维持情况。使用小型猪滑车缺损模型评估双膦酸盐增强储存培养基对新鲜骨软骨组织体内整合的影响,通过μCT和脱钙组织学对其进行量化。在体外研究中,番红O/固绿染色显示,低剂量和高剂量含氮处理的移植物在储存长达43天时均保留了软骨细胞活力和软骨基质。储存在含氮增强储存培养基中的同种异体移植物在小型猪滑车缺损模型中显示出μCT和组织学证据,表明体内骨和软骨整合增强。几项临床前研究表明,通过添加相对常见的药物和生物分子,有可能增强新鲜骨软骨同种异体移植物的储存。这项研究表明,在标准储存培养基中添加含氮双膦酸盐可能会改善冷藏期间软骨细胞活力和移植物结构的维持,并增强移植物在体内的骨和软骨整合。[《矫形外科学》:2018年;41(3):e376-e382。]

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