ISS: Engineering Multiple-Compartment Cartilage Tissue Construct for Space and Terrestrial Applications

人体肌肉骨骼系统对生物力学提示很敏感。机械刺激对软骨健康很重要。缺乏生物力学载荷会导致关节软骨腐烂。我们的天然软骨自我修复能力有限。因此，软骨组织退变后如何再生是一个巨大的挑战。在地球上，长时间的关节固定会导致软骨退化。在微重力下，类似的生物力学载荷的缺失可能也会损害软骨组织和细胞。在这项工作中，我们将开发一种工程化软骨组织结构，以克服在微重力下假定的软骨退化。这项工作将提高我们对微重力对软骨影响的理解，从而使地球上的生命受益。这项工作的结果可能会导致治疗软骨损伤的新疗法。这项工作的成果也将有利于宇航员返回地球时的健康。此外，这项研究的结果将被用来向本科生和研究生介绍组织工程和纳米医学。此外，这项工作将通过鼓励代表性不足的学生从事科学和工程工作来增加生物医学工程师的多样性。还计划为初中生/高中生和普通公众开展更多的外展活动。机械刺激对维持软骨形成(分化为软骨)和软骨内环境稳定(保持健康)至关重要；缺乏生物力学负荷会导致关节软骨的退化。由于天然软骨具有有限的自我修复能力，其退化后如何再生是一个巨大的挑战。在地球上，长时间的关节固定会导致软骨细胞的分解代谢(破坏)活动和随后的软骨退化。在太空中，微重力造成的生物力学负荷的缺失很可能也会破坏软骨细胞的功能和软骨的动态平衡。如果我们能够设计一种软骨组织结构来克服在微重力下假定的软骨退化，这也应该会改善地球上的组织工程研究和医疗保健。这项工作将创造一种结构，它可以自动为自己供应机械响应的microRNA，作为恢复软骨细胞软骨生成的治疗方法。结果将是一个长期的(动态平衡)软骨组织结构，以长期维持软骨细胞的软骨生成和动态平衡。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The human musculoskeletal system is sensitive to biomechanical cues. Mechanical stimulation is important to cartilage health. An absence of biomechanical loading causes articular cartilage to decay. Our natural cartilage has limited ability to repair itself. Therefore, it is a significant challenge to regenerate authentic cartilage tissue after it degenerates. On Earth, prolonged joint immobilization can cause cartilage degradation. In microgravity, the similar absence of biomechanical loading caused likely also damages cartilage tissue and cells. In this work, we will develop an engineered cartilage tissue construct to overcome the presumed degradation of cartilage in microgravity. This work will benefit life on Earth by improving our understanding of the effects of microgravity on cartilage. The results of this work may lead to new therapies to treat cartilage injuries. The results of this work will also benefit astronauts’ health when they return to Earth. Furthermore, outcomes of this study will be used to introduce undergraduate and graduate engineering students to tissue engineering and nanomedicine. In addition, this work will increase diversity among biomedical engineers by encouraging underrepresented students to engage in science and engineering. Additional outreach activities are planned for middle/high school students and the general public. Mechanical stimulation is critical to maintain chondrogenesis (differentiation into cartilage) and cartilage homeostasis (health maintenance); an absence of biomechanical loading results in degradation of articular cartilage. Because natural cartilage has limited self-repair ability, it is a significant challenge to regenerate authentic cartilage tissue after it degenerates. On Earth, prolonged joint immobilization can cause catabolic (breakdown) activities of chondrocyte and subsequent cartilage degradation. In space, the absence of biomechanical loading caused by microgravity most likely also damages chondrocyte function and cartilage homeostasis. If we can engineer a cartilage tissue construct to overcome the presumed degradation of cartilage in microgravity, it should also improve tissue engineering research and healthcare on Earth. This work will create a construct which can automatically supply itself with mechano-responsive microRNA as a therapy to restore cartilage cell chondrogenesis. The result will be a long-lasting (homeostatic) cartilage tissue construct to maintain cartilage cell chondrogenesis and homeostasis in the long term.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.