Pure chondral defects represent the most clinically significant articular cartilage injuries. To inform the development of clinically suitable tissue-engineering strategies for chondral repair using cells from a human patient, the combination of human stem cells (HSCs), biomaterial scaffolds, and growth factors has been widely harnessed in preclinical animal models. Due to the large heterogeneity in study designs and outcome reporting in such studies, we aimed to systematically review literature pertaining to HSC based tissue engineering strategies in animal models of chondral repair such that trends may be identified and the utility of HSCs in chondral repair can be elucidated. An extensive search strategy was carried out through PubMed, MEDLINE, and EMBASE databases to identify relevant studies. Initially the title and abstract of 787 studies were screened after which inclusion and exclusion criteria sorted 56 studies for full-text evaluation. Following full text review, a final number of 22 articles were included. Out of 22 included studies, 16 used scaffold implantation, 2 used cell pellet implantation, and 4 used intra-articular injection to administer HSCs to the region of chondral defects. HSC-containing implants outperformed scaffold-only or untreated control groups in both large and small animals for chondral regeneration. Umbilical cord mesenchymal stem cells and hyaluronic acid-containing scaffolds emerged as popular stem cell and scaffold choices, respectively. However, the short analysis timepoints post cell implantation was a key limitation in many studies. This review highlights the versatility of HSCs in achieving chondral regeneration in vivo and the enhancement of chondral repair through the selection of appropriate three-dimensional scaffolds and growth factors which are essential to support cell growth, attachment, migration, and extracellular matrix synthesis. Considerable heterogeneity exists in outcome reporting, and only one article reported biomechanical evaluation of neocartilage. Standardized outcome reporting systems that include comprehensive biomechanical testing protocols should be utilized in future in vivo studies of cartilage tissue engineering as the biomechanical quality of neocartilage is of great functional significance.

中文翻译：

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用于体内软骨修复的基于人类干细胞的组织工程：系统评价

纯软骨缺损代表了临床上最显着的关节软骨损伤。为了使用人类患者的细胞开发临床合适的软骨修复组织工程策略，人类干细胞 (HSC)、生物材料支架和生长因子的组合已在临床前动物模型中得到广泛利用。由于此类研究中研究设计和结果报告的巨大异质性，我们旨在系统地审查有关软骨修复动物模型中基于 HSC 的组织工程策略的文献，以便可以确定趋势，并且可以确定 HSC 在软骨修复中的效用阐明。通过 PubMed、MEDLINE 和 EMBASE 数据库进行了广泛的搜索策略，以确定相关研究。最初筛选了 787 项研究的标题和摘要，然后根据纳入和排除标准对 56 项研究进行了全文评估。经过全文审查，最终收录了22篇文章。在 22 项纳入的研究中，16 项使用支架植入，2 项使用细胞颗粒植入，4 项使用关节内注射将 HSC 施用于软骨缺损区域。在大型和小型动物中，含有 HSC 的植入物在软骨再生方面的表现优于仅使用支架或未经处理的对照组。脐带间充质干细胞和含有透明质酸的支架分别成为流行的干细胞和支架选择。然而，在许多研究中，细胞植入后的短分析时间点是一个关键限制。通过选择适当的三维支架和生长因子来促进体内软骨修复和增强软骨修复，这些支架和生长因子对于支持细胞生长、附着、迁移和细胞外基质合成至关重要。结果报告存在相当大的异质性，只有一篇文章报道了新软骨的生物力学评估。由于新软骨的生物力学质量具有重要的功能意义，因此在未来的软骨组织工程体内研究中应使用包括综合生物力学测试方案在内的标准化结果报告系统。