McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Tissue Eng Part A. 2021 Feb;27(3-4):214-222. doi: 10.1089/ten.TEA.2020.0123. Epub 2020 Nov 2.
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 . 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 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.
尽管在软骨组织工程领域取得了显著进展,但工程化具有均匀性能的软骨构建体仍然是一个挑战。此外,为了使工程化软骨进入临床,这种均匀的生长必须以高效的方式发生。在这项研究中,我们研究了增加培养基体积的潜力,以加速间充质干细胞 (MSC) 负载的工程化构建体随时间均匀成熟。我们在软骨形成培养 4 周和 8 周后使用体力学、组织学和生物化学测量来评估 MSC 负载的构建体。这些分析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,以量化整个构建体中的深度依赖性机械性能。我们的发现表明,增加培养基体积可以在培养早期促进基质沉积,并在稍后的时间点改善不必要的区域异质性。总之,这些数据支持在培养过程中使用更高的培养基体积来加速组织成熟并增加组织构建体的核心强度。这些发现将推动软骨组织工程和组织工程化构建体的转化。