Towards the scale up of tissue engineered intervertebral discs for clinical application.
Towards the scale up of tissue engineered intervertebral discs for clinical application.
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DOI：
10.1016/j.actbio.2018.01.050
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发表时间：
2018-04-01
影响因子：
9.7
通讯作者：
Smith HE
中科院分区：
文献类型：
--
作者：
Gullbrand SE;Kim DH;Bonnevie E;Ashinsky BG;Smith LJ;Elliott DM;Mauck RL;Smith HE
用一种可存活的、模仿天然组织结构和功能的组织工程化结构来替代融合术或机械关节成形术是治疗腰椎间盘病变的一种有吸引力的选择。虽然已经开发了一些工程化的椎间盘，但这些结构的平均大小仍然是人类椎间盘大小的一小部分。在这项研究中，我们制作了中等尺寸(3 mm高x 10 mm直径)和大尺寸(6 mm高x 20 mm直径)的盘状角度铺层结构(DAP)，涵盖了从兔腰椎到人颈椎的尺寸尺度。通过量化细胞活性和代谢活性、构建生化含量、磁共振T2值和机械性能来评估这些工程化盘在培养15周内的成熟度。为了评估DAP在体内空间的性能，将预先培养的DAP植入无菌大鼠皮下5周。我们的研究结果表明，在体外培养过程中，大小的DAP在功能和成分上都成熟了，机械性能和生化含量随着时间的推移而增加，但与中等大小的DAP相比，大的DAP表现不佳。皮下植入导致两种大小的NP细胞活性和GAG含量降低，而对AF生化或代谢活动几乎没有影响。这些发现表明，在体外培养过程中，大尺寸的工程化盘将会成熟，然而，未来的工作将需要解决细胞活性降低和整个构建过程中基质分布不均的挑战。
Replacement of the intervertebral disc with a viable, tissue-engineered construct that mimics native tissue structure and function is an attractive alternative to fusion or mechanical arthroplasty for the treatment of disc pathology. While a number of engineered discs have been developed, the average size of these constructs remains a fraction of the size of human intervertebral discs. In this study, we fabricated medium (3 mm height x 10 mm diameter) and large (6 mm height x 20 mm diameter) sized disc-like angle ply structures (DAPS), encompassing size scales from the rabbit lumbar spine to the human cervical spine. Maturation of these engineered discs was evaluated over 15 weeks in culture by quantifying cell viability and metabolic activity, construct biochemical content, MRI T2 values, and mechanical properties. To assess the performance of the DAPS in the in vivo space, pre-cultured DAPS were implanted subcutaneously in athymic rats for 5 weeks. Our findings show that both sized DAPS matured functionally and compositionally during in vitro culture, as evidenced by increases in mechanical properties and biochemical content over time, yet large DAPS under-performed compared to medium DAPS. Subcutaneous implantation resulted in reductions in NP cell viability and GAG content at both size scales, with little effect on AF biochemistry or metabolic activity. These findings demonstrate that engineered discs at large size scales will mature during in vitro culture, however, future work will need to address the challenges of reduced cell viability and heterogeneous matrix distribution throughout the construct.
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影响因子：
3.1
作者：
Farrell, Megan J.;Comeau, Eric S.;Mauck, Robert L.
通讯作者：
Mauck, Robert L.
影响因子：
3.7
作者：
Choy AT;Chan BP
通讯作者：
Chan BP
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2.4
作者：
Huang AH;Farrell MJ;Mauck RL
通讯作者：
Mauck RL
影响因子：
9.7
作者：
Kim, Minwook;Farrell, Megan J.;Mauck, Robert L.
通讯作者：
Mauck, Robert L.
影响因子：
2.9
作者：
CASSIDY, JJ;HILTNER, A;BAER, E
通讯作者：
BAER, E