3B's Research Group-Biomaterials, Biodegradables and Biomimetics, Minho University, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal.
Arthroscopy. 2011 Dec;27(12):1706-19. doi: 10.1016/j.arthro.2011.08.283. Epub 2011 Oct 21.
The aim of this systematic review was to address tissue engineering and regenerative medicine (TERM) strategies applied to the meniscus, specifically (1) clinical applications, indications, results, and pitfalls and (2) the main trends in research assessed by evaluation of preclinical (in vivo) studies.
Three independent reviewers performed a search on PubMed, from 2006 to March 31, 2011, using the term "meniscus" with all of the following terms: "scaffolds," "constructs," "cells," "growth factors," "implant," "tissue engineering," and "regenerative medicine." Inclusion criteria were English language-written, original clinical research (Level of Evidence I to IV) and preclinical studies of TERM application in knee meniscal lesions. Reference lists and related articles on journal Web sites of selected articles were checked until prepublication for potential studies that could not be identified eventually by our original search. The modified Coleman Methodology score was used for study quality analysis of clinical trials.
The PubMed search identified 286 articles (a similar search from 2000 to 2005 identified 161 articles). Non-English-language articles (n = 9), Level V publications (n = 19), in vitro studies (n = 118), and 102 studies not related to the topic were excluded. One reference was identified outside of PubMed. Thirty-eight references that met the inclusion criteria were identified from the original search. On the basis of our prepublication search, 2 other references were included. A total of 9 clinical and 31 preclinical studies were selected for further analysis. Of the clinical trials, 1 was classified as Level I, 2 as Level II, and 6 as Level IV. Eight referred to acellular scaffold implantation for partial meniscal replacement, and one comprised fibrin clot application. The mean modified Coleman Methodology score was 48.0 (SD, 15.7). Of the preclinical studies, 11 original works reported on studies using large animal models whereas 20 research studies used small animals. In these studies the experimental design favored cell-seeded scaffolds or scaffolds enhanced with growth factors (GFs) in attempts to improve tissue healing, as opposed to the plain acellular scaffolds that were predominant in clinical trials. Injection of mesenchymal stem cells and gene therapy are also presented as alternative strategies.
Partial meniscal substitution using acellular scaffolds in selected patients with irreparable loss of tissue may be a safe and promising procedure. However, there is only 1 randomized controlled study supporting its application, and globally, many methodologic issues of published trials limit further conclusions. We registered a different trend in preclinical trials, with most considering augmentation of scaffolds by cells and/or GFs, as opposed to the predominantly acellular approach in clinical trials. Different TERM approaches to enhance meniscal repair or regeneration are in preclinical analysis, such as the use of mesenchymal stem cells, gene therapy, and GFs alone or in combination, and thus could be considered in the design of subsequent trials.
Level IV, systematic review of Level I to IV studies.
本系统评价旨在探讨应用于半月板的组织工程和再生医学（TERM）策略，具体包括：（1）临床应用、适应证、结果和陷阱；（2）通过评估临床前（体内）研究来评估研究的主要趋势。
三位独立的评审员在 2006 年至 2011 年 3 月 31 日期间，在 PubMed 上使用“半月板”一词，结合以下所有术语进行了搜索：“支架”、“构建体”、“细胞”、“生长因子”、“植入物”、“组织工程”和“再生医学”。纳入标准为英文原创临床研究（证据水平 I 至 IV）和膝关节半月板损伤的 TERM 应用的临床前研究。检查选定文章的期刊网站上的参考文献列表和相关文章，直到预出版，以查找最终无法通过我们原始搜索确定的潜在研究。临床研究的改良 Coleman 方法评分用于研究质量分析。
PubMed 搜索共确定了 286 篇文章（类似的 2000 年至 2005 年的搜索确定了 161 篇文章）。排除了非英语文章（n=9）、V 级出版物（n=19）、体外研究（n=118）和 102 篇与主题无关的文章。从 PubMed 以外的地方找到了 1 篇参考文献。从最初的搜索中确定了 38 篇符合纳入标准的参考文献。基于我们的预出版搜索，又确定了 2 篇参考文献。共选择了 9 项临床研究和 31 项临床前研究进行进一步分析。在临床试验中，1 项为 I 级，2 项为 II 级，6 项为 IV 级。其中 8 项涉及用于部分半月板置换的去细胞支架植入，1 项涉及纤维蛋白凝块应用。改良 Coleman 方法评分的平均值为 48.0（SD，15.7）。在临床前研究中，11 项原始研究报告了使用大动物模型的研究，而 20 项研究使用了小动物。在这些研究中，实验设计偏向于细胞接种支架或用生长因子（GFs）增强的支架，以试图改善组织愈合，而临床试验中主要是单纯的去细胞支架。间充质干细胞注射和基因治疗也被提出作为替代策略。
在特定组织丧失不可修复的患者中，使用去细胞支架进行部分半月板置换可能是一种安全且有前途的方法。但是，只有 1 项随机对照研究支持其应用，而且全球范围内，许多已发表试验的方法学问题限制了进一步的结论。我们在临床前试验中观察到了不同的趋势，大多数试验考虑通过细胞和/或 GFs 增强支架，而不是临床试验中主要的去细胞方法。不同的 TERM 方法可增强半月板修复或再生，例如单独或联合使用间充质干细胞、基因治疗和 GFs，因此可以在随后的试验设计中考虑这些方法。
IV 级，对 I 至 IV 级研究的系统评价。
