软骨修复策略旨在修复骨软骨组织类似于天然软骨的病变,但通常会观察到多种修复组织。组织学是重要的结构结果,可以作为随机对照临床研究中疗效的临时指标。本文的目的是为动物组织和人体活检的标准化组织处理和无偏见评估提出指南。方法是根据文献综述汇编而成的,并添加了说明性数据。在动物模型中,治疗通常用于健康组织中产生的急性缺陷,可以在多个术后时间点分析整个关节。在人类临床治疗中,治疗适用于发展的病变,并获得活检,通常来自一部分患者,在一个特定的时间点。努力标准化软骨修复研究中的结构终点评估,应控制5个变量:1)活检/样本切片的位置,2)活检/样本回收的时间安排,3)直方图处理,4)染色,和5)用适当的对照组进行盲法评估。组织学评分,修复组织厚度的定量组织形态计量学,胶原蛋白和糖胺聚糖的组织染色百分比,偏振光显微镜对胶原蛋白原纤维组织,和软骨下骨整合/结构都是相关的结果指标,可以收集并用于评估新疗法的疗效。标准化的组织学方法可以改善统计分析,帮助解释和验证非侵入性成像结果,并允许研究之间的交叉比较。目前,在评估修复组织质量和软骨特性方面,没有合适的组织学替代品。
Cartilage repair strategies aim to resurface a lesion with osteochondral tissue resembling native cartilage, but a variety of repair tissues are usually observed. Histology is an important structural outcome that could serve as an interim measure of efficacy in randomized controlled clinical studies. The purpose of this article is to propose
guidelines for standardized histoprocessing and unbiased evaluation of animal tissues and human biopsies. Methods were compiled from a literature review, and illustrative data were added. In animal models, treatments are usually administered to acute defects created in healthy tissues, and the entire joint can be analyzed at multiple postoperative time points. In human clinical therapy, treatments are applied to developed lesions, and biopsies are obtained, usually from a subset of patients, at a specific time point. In striving to standardize evaluation of structural endpoints in cartilage repair studies, 5 variables should be controlled: 1) location of biopsy/sample section, 2) timing of biopsy/sample recovery, 3) histoprocessing, 4) staining, and 5) blinded evaluation with a proper control group. Histological scores, quantitative histomorphometry of repair tissue thickness, percentage of tissue staining for collagens and glycosaminoglycan, polarized light microscopy for collagen fibril organization, and subchondral bone integration/structure are all relevant outcome measures that can be collected and used to assess the efficacy of novel therapeutics. Standardized histology methods could improve statistical analyses, help interpret and validate noninvasive imaging outcomes, and permit cross-comparison between studies. Currently, there are no suitable substitutes for histology in evaluating repair tissue quality and cartilaginous character.