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

ISS：为太空和陆地应用设计多室软骨组织结构

• 批准号: 2025362
• 负责人: Yupeng Chen
• 金额: $ 40万
• 依托单位: University of Connecticut
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2025362&HistoricalAwards=false
• 关键词: ISS; Engineering; Multiple; Compartment; Cartilage

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.

人体肌肉骨骼系统对生物力学信号很敏感，缺乏生物力学负荷会导致关节软骨的自我修复能力有限，因此，再生真正的软骨是一个重大挑战。在地球上，长时间的关节固定会导致软骨退化，在微重力下，类似的生物力学负荷的缺失也可能导致软骨退化。在这项工作中，我们将开发一种工程化的软骨组织结构，以克服微重力下软骨的退化问题。这项工作将通过提高我们对微重力对软骨影响的了解而造福于地球上的生命。这项工作可能会带来治疗软骨损伤的新疗法，这项工作的结果也将有益于宇航员返回地球时的健康。此外，这项研究的成果将用于向本科生和研究生介绍组织。此外，这项工作将通过鼓励代表性不足的学生参与科学和工程来增加生物医学工程师的多样性。机械刺激对于维持软骨形成至关重要。分化为软骨）和软骨稳态（健康维持）；缺乏生物力学负荷会导致关节软骨退化，因为天然软骨的自我修复能力有限，因此它是一种软骨。在地球上，软骨组织退化后再生是一个重大挑战，长时间的关节固定会导致软骨细胞的分解代谢（分解）活动以及随后的软骨退化，在太空中，微重力引起的生物力学负荷的缺失很可能也会损害软骨细胞的功能和软骨。如果我们能够设计出一种软骨组织结构来克服微重力下软骨的退化问题，那么它也应该能够改善组织工程研究。这项工作将创建一种能够自动为自身提供机械响应 microRNA 的结构，作为恢复软骨细胞软骨形成的疗法，其结果将是一种持久（稳态）的软骨组织结构，以维持软骨细胞软骨形成和功能。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

A structural and functional comparison between two recombinant human lubricin proteins: Recombinant human proteoglycan-4 (rhPRG4) vs ECF843

两种重组人润滑素蛋白之间的结构和功能比较：重组人蛋白聚糖 4 (rhPRG4) 与 ECF843

• DOI: 10.1016/j.exer.2023.109643
• 发表时间: 2023
• 期刊: Experimental Eye Research
• 影响因子: 3.4
• 作者: Menon, Nikhil G.;Tanguay, Adam P.;Zhou, Libo;Zhang, Ling X.;Bobst, Cedric E.;Han, Mingyu;Ghosh, Mallika;Greene, George W.;Deymier, Alix;Sullivan, Benjamin D.
• 通讯作者: Sullivan, Benjamin D.

Development of Engineered Cartilage Tissue Construct Maintaining Healthy Function of Cartilage Cell

开发维持软骨细胞健康功能的工程软骨组织结构

• 发表时间: 2023
• 期刊: Trans Orthop Res Soc
• 作者: Anne Yau, Ian Sands

Blood-brain-barrier modeling with tissue chips for research applications in space and on Earth

• DOI: 10.3389/frspt.2023.1176943
• 发表时间: 2023-08-09
• 期刊: FRONTIERS IN SPACE TECHNOLOGIES
• 作者: Yau，Anne;Jogdand，Aditi;Chen，Yupeng
• 通讯作者: Chen，Yupeng

Nanomedicine strategies for central nervous system (CNS) diseases

• DOI: 10.3389/fbiom.2023.1215384
• 发表时间: 2023-08
• 期刊: Frontiers in biomaterials science
• 作者: Shreya Nagri;Olivia Rice;Yupeng Chen

A Library of Janus Base Nano-Matrices for Tissue Engineering

用于组织工程的 Janus 基础纳米基质库

• 发表时间: 2022
• 期刊: Trans Orthop Res Soc
• 作者: Anne Yau, Libo Zhou