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绵羊体内基质诱导自体软骨细胞植入:包括共聚焦关节镜检查在内的客观评估

Matrix-induced autologous chondrocyte implantation in sheep: objective assessments including confocal arthroscopy.

作者信息

Jones C W, Willers C, Keogh A, Smolinski D, Fick D, Yates P J, Kirk T B, Zheng M H

机构信息

School of Mechanical Engineering, University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia.

出版信息

J Orthop Res. 2008 Mar;26(3):292-303. doi: 10.1002/jor.20502.

Abstract

The assessment of cartilage repair has largely been limited to macroscopic observation, magnetic resonance imaging (MRI), or destructive biopsy. The aims of this study were to establish an ovine model of articular cartilage injury repair and to examine the efficacy of nondestructive techniques for assessing cartilage regeneration by matrix-induced autologous chondrocyte implantation (MACI). The development of nondestructive assessment techniques facilitates the monitoring of repair treatments in both experimental animal models and human clinical subjects. Defects (Ø 6 mm) were created on the trochlea and medial femoral condyle of 21 sheep randomized into untreated controls or one of two treatment arms: MACI or collagen-only membrane. Each group was divided into 8-, 10-, and 12-week time points. Repair outcomes were examined using laser scanning confocal arthroscopy (LSCA), MRI, histology, macroscopic ICRS grading, and biomechanical compression analysis. Interobserver analysis of the randomized blinded scoring of LSCA images validated our scoring protocol. Pearson correlation analysis demonstrated the correlation between LSCA, MRI, and ICRS grading. Testing of overall treatment effect independent of time point revealed significant differences between MACI and control groups for all sites and assessment modalities (Asym Sig < 0.05), except condyle histology. Biomechanical analysis suggests that while MACI tissue may resemble native tissue histologically in the early stages of remodeling, the biomechanical properties remain inferior at least in the short term. This study demonstrates the potential of a multisite sheep model of articular cartilage defect repair and its assessment via nondestructive methods.

摘要

软骨修复的评估在很大程度上局限于宏观观察、磁共振成像(MRI)或有创活检。本研究的目的是建立一个关节软骨损伤修复的绵羊模型,并通过基质诱导自体软骨细胞植入(MACI)来检验非侵入性技术评估软骨再生的效果。非侵入性评估技术的发展有助于在实验动物模型和人类临床受试者中监测修复治疗。在21只绵羊的滑车和股骨内侧髁上制造缺损(直径6毫米),随机分为未治疗对照组或两个治疗组之一:MACI组或仅使用胶原膜组。每组再分为8周、10周和12周三个时间点。使用激光扫描共聚焦关节镜检查(LSCA)、MRI、组织学、宏观国际软骨修复协会(ICRS)分级和生物力学压缩分析来检查修复结果。对LSCA图像随机盲法评分的观察者间分析验证了我们的评分方案。Pearson相关性分析显示了LSCA、MRI和ICRS分级之间的相关性。对不考虑时间点的总体治疗效果进行测试发现,除髁部组织学外,MACI组与对照组在所有部位和评估方式上均存在显著差异(不对称显著性<0.05)。生物力学分析表明,虽然MACI组织在重塑早期组织学上可能类似于天然组织,但至少在短期内其生物力学性能仍然较差。本研究证明了关节软骨缺损修复多部位绵羊模型及其通过非侵入性方法进行评估的潜力。

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