Kon Elizaveta, Roffi Alice, Filardo Giuseppe, Tesei Giulia, Marcacci Maurilio
II Clinic-Biomechanics Laboratory and Nano-Biotechnology Laboratory, Rizzoli Orthopaedic Institute, Bologna, Italy.
Nano-Biotechnology Laboratory, Rizzoli Orthopaedic Institute, Bologna, Italy.
Arthroscopy. 2015 Apr;31(4):767-75. doi: 10.1016/j.arthro.2014.11.017. Epub 2015 Jan 27.
Regenerative scaffold-based procedures are emerging as a potential therapeutic option for the treatment of chondral and osteochondral lesions. In general, we can summarize most of the recent developments to reach clinical application into 2 major trends: the use of different cell sources or the application of biomaterials as a cell-free approach. The aim of this systematic review was to analyze both preclinical and clinical studies on these new trends to understand how the available evidence supports the use of cell sources or justifies the cell-free approach for the scaffold-based treatment of cartilage lesions.
The research was performed using the PubMed database by looking at studies published in the English language referring to chondral or osteochondral defect repair with scaffold-based procedures until the end of 2013. The following strings were used: ("cartilage"[MeSH] AND "tissue scaffolds"[MeSH]).
The search showed an increasing number of published articles each year for both scaffold-based approaches, identifying a total of 305 articles. Among clinical trials, 116 used cell-based scaffold treatments and 11 used scaffolds alone. In the preclinical setting, a scaffold/cell combination was the most used treatment approach (133 v 45 articles), with mesenchymal stem cells (MSCs) being the favorite cell type. Bone marrow was the most used cell source, but other sources are gaining interest. Among articles comparing scaffolds with or without cells, the majority reported superior results for cells (71 of 89 articles). In the clinical setting, most of the articles analyzed chondrocyte-based scaffolds, with only 7 studies using MSCs; all cells were from bone marrow. Despite the lower number of articles, cell-free scaffolds are gaining popularity, with a recent increase in published studies showing promising results.
This systematic review underlined the difficulties in understanding the real need for cells to increase the scaffold-based cartilage healing potential because of the heterogeneity of products used as well as the design of the published studies. Scaffold and cell combinations were the most investigated option in the preclinical setting, showing generally superior results, but in the clinical setting, both strategies remain used. In particular, although chondrocytes are the most commonly used cell type, research showed increasing interest in the potential of MSCs for cartilage regeneration. However, the difficulties in managing cell cultures, together with the development of a new generation of materials able to exploit the intrinsic tissue regeneration ability, justifies the clinical use of cell-free scaffolds, with increasing literature and promising preliminary results.
Level IV, systematic review of Level I to IV studies.
基于再生支架的治疗方法正逐渐成为治疗软骨和骨软骨损伤的一种潜在治疗选择。总体而言，我们可以将近期大多数已取得临床应用进展的研究总结为两大趋势：使用不同的细胞来源或应用生物材料作为无细胞治疗方法。本系统评价的目的是分析关于这些新趋势的临床前和临床研究，以了解现有证据如何支持细胞来源的使用或证明基于支架治疗软骨损伤的无细胞方法的合理性。
通过检索PubMed数据库进行研究，检索截至2013年底以英文发表的关于使用基于支架的方法修复软骨或骨软骨缺损的研究。使用了以下检索词：（“软骨”[医学主题词] AND “组织支架”[医学主题词]）。
检索显示，两种基于支架的方法每年发表的文章数量都在增加，共识别出305篇文章。在临床试验中，116项使用基于细胞的支架治疗，11项仅使用支架。在临床前研究中，支架/细胞组合是最常用的治疗方法（133篇对45篇文章），间充质干细胞（MSCs）是最受欢迎的细胞类型。骨髓是最常用的细胞来源，但其他来源也越来越受到关注。在比较有细胞和无细胞支架的文章中，大多数报告细胞治疗效果更佳（89篇文章中的71篇）。在临床研究中，大多数文章分析了基于软骨细胞的支架，只有7项研究使用了MSCs；所有细胞均来自骨髓。尽管文章数量较少，但无细胞支架越来越受欢迎，近期发表的研究数量增加，显示出有前景的结果。
本系统评价强调，由于所用产品的异质性以及已发表研究的设计，难以理解增加基于支架的软骨愈合潜力对细胞的实际需求。支架和细胞组合是临床前研究中研究最多的选择，总体显示出更佳的结果，但在临床研究中，两种策略仍在使用。特别是，尽管软骨细胞是最常用的细胞类型，但研究表明对MSCs在软骨再生方面的潜力兴趣日益增加。然而，细胞培养管理的困难，以及新一代能够利用组织内在再生能力的材料的开发，证明了无细胞支架临床应用的合理性，相关文献不断增加且初步结果很有前景。
IV级，对I至IV级研究的系统评价。
