Despite marked advances in the field of cartilage tissue engineering, it remains a challenge to engineer cartilage constructs with homogeneous properties. Moreover, for engineered cartilage to make it to the clinic, this homogeneous growth must occur in a time-efficient manner. In this study we investigated the potential of increased media volume to expedite the homogeneous maturation of mesenchymal stem cell (MSC) laden engineered constructs over time in vitro. We assessed the MSC-laden constructs after 4 and 8 weeks of chondrogenic culture using bulk mechanical, histological, and biochemical measures. These assays were performed on both the intact total constructs and the construct cores to elucidate region-dependent differences. In addition, local strain transfer was assessed to quantify depth-dependent mechanical properties throughout the constructs. Our findings suggest that increased media volume enhances matrix deposition early in culture and ameliorates unwanted regional heterogeneities at later time points. Taken together, these data support the use of higher media volumes during in vitro culture to hasten tissue maturation and increase the core strength of tissue constructs. These findings will forward the field of cartilage tissue engineering and the translation of tissue engineered constructs.

中文翻译：

---

优化的培养基体积使基于间充质干细胞的工程软骨构建体均匀生长

尽管软骨组织工程领域取得了显着进展，但设计具有均质特性的软骨结构仍然是一个挑战。此外，为了使工程软骨进入临床，这种均匀生长必须以一种省时的方式进行。在这项研究中，我们研究了增加培养基体积以加速载有间充质干细胞 (MSC) 的工程构建体在体外随时间均匀成熟的潜力. 我们使用大量机械、组织学和生化措施评估了 4 和 8 周的软骨形成培养后的 MSC 负载结构。这些测定在完整的总构建体和构建体核心上进行，以阐明区域依赖性差异。此外，还评估了局部应变传递以量化整个结构中与深度相关的机械性能。我们的研究结果表明，增加的培养基体积会在培养早期增强基质沉积，并在后期改善不需要的区域异质性。总之，这些数据支持在体外使用更高的培养基体积培养以加速组织成熟并增加组织结构的核心强度。这些发现将推动软骨组织工程领域和组织工程结构的转化。