Novel Strategies in Cartilage Tissue Engineering: Enhancing Cartilage Stability Using Muscle-Derived Factors and Scaffold Selection

0966920增肌纤维是一种自我修复能力差的组织。目前的组织工程策略旨在通过将软骨细胞或软骨细胞接种到三维支架中来替代受损组织。 在支架内，这些软骨细胞增殖并分泌细胞外基质，导致再生软骨的形成。然后将再生的软骨移植到宿主体内，目的是承担天然软骨的功能。工程化软骨的生物力学强度与软骨细胞产生的细胞外基质的量直接相关。然而，即使是具有良好机械性能的再生软骨也可能被宿主部位中存在的促炎细胞因子损伤，从而损害再生软骨的稳定性。因此，迫切需要工程化软骨能够抵抗促炎激素诱导的降解。智力价值。这项跨学科研究结合了发育生物学（曾博士）和组织工程（卡普兰博士）的专业知识。它旨在解决软骨组织工程技术中的关键问题，通过测试的中心假设，即肌肉细胞和支架选择可以增强再生软骨的稳定性，在软骨基质的生产和炎症细胞因子的抵抗。计划进行一系列全面的生物化学和生物力学分析来检验这一假设。关于肌细胞调节软骨基因表达的机制知之甚少，肌细胞或支架材料对细胞因子反应的作用从未报道过。因此，除了推进软骨组织工程技术，完成这项研究还将导致更深入和更完整的了解软骨调节的生物学。本提案中描述的策略受到动物发育概念的启发，当组织彼此并行发育时软骨和肌肉等组织在相邻组织之间的细胞-细胞信号传导及其随后的分化和增殖中起着至关重要的作用。因此，软骨形成不仅涉及软骨细胞，而且涉及多种周围组织的细胞。因此，我们模仿胚胎发育的想法可能会激发创造新的策略来设计其他组织类型。更广泛的影响。这项拟议的研究旨在促进教育和学习，以及科学知识。两个新的模块被设计成两个课程（即生物材料和组织工程和发育生物学），这将侧重于使用发育生物学的概念和方法来增强软骨组织工程，并使用组织工程方法来概括和研究发育过程。课程将分为课堂讲座、学生报告和文学阅读。曾博士和卡普兰博士都参加了各种教育项目，如TAHSS（教师和高中生）和BDBS（生物医学科学的多样性建设）。这些计划招收少数民族或经济上处于不利地位的学生，否则他们可能没有机会接触研究。研究计划的教育部分经过精心设计，使不同水平的学生能够在两个实验室进行跨学科研究。拟议的研究活动还将加强科学界的基础设施。首先，这项工作将直接有利于塔夫茨大学的当地社区。特别是，它将有助于塔夫茨生物工程和生物技术中心的基础设施。通过其教育和培训计划，该中心将学术界（学生，博士后和教师）以及学术界和工业界之间的成员联系起来。此外，从这项研究中获得的结果将通过出版物，并在全国各地的会议和研究研讨会上与其他科学家分享。因此，这项研究所产生的活动也将对广大科学界产生积极影响。

0966920ZengCartilage is a tissue that has a poor capacity for self-repair. Current tissue engineering strategies aim to replace damaged tissue by seeding cartilage cells or chondrocytes into three-dimensional scaffolds. Within the scaffolds, these chondrocytes proliferate and secrete extracellular matrix, leading to the formation of regenerated cartilage. This regenerated cartilage will then be transplanted into the host, with the goal of assuming the function of native cartilage. The biomechanical strength of engineered cartilage is directly correlated to the amount of extracellular matrix produced by cartilage cells. Yet, even regenerated cartilage with good mechanical properties may be damaged by pro-inflammatory cytokines present in the host site, compromising the stability of the regenerated cartilage. Thus, there is a critical need for engineered cartilage to be resistant to pro-inflammatory cytokine-induced degradation.Intellectual merit.This interdisciplinary research combines the expertise of developmental biology (Dr. Zeng) with tissue engineering (Dr. Kaplan). It aims at solving key issues in the technology of cartilage tissue engineering by testing the central hypothesis that muscle cells and scaffolding selection can enhance the stability of regenerated cartilage in terms of cartilage matrix production and inflammatory cytokine resistance. A comprehensive battery of biochemical and biomechanical analyses are planned to test this hypothesis. Very little is known regarding the mechanism by which muscle cells regulate cartilage gene expression, and the role of muscle cells or scaffolding materials on cytokine response has never been reported. Thus in addition to advancing cartilage tissue engineering technology, completing this research will also lead to a deeper and more complete understanding of the biology of cartilage regulation.The strategy described in this proposal was inspired by concepts from animal development, when tissues develop alongside each other (such as cartilage and muscle) play crucial roles in cell-cell signaling between adjacent tissues and their subsequent differentiation and proliferation. Thus, cartilage formation involves not just cartilage cells, but cells of multiple surrounding tissues. Thus our idea of mimicking embryo development may inspire the creation of novel strategies to engineer other tissue types as well.Broader impacts.This proposed research seeks to advance education and learning in addition to the knowledge of science. Two new modules are designed to build into two courses (i.e. Biomaterial and tissue engineering and Developmental Biology), which will focus on enhancing cartilage tissue engineering using the concepts and approaches in developmental biology, and using tissue engineering approaches to recapitulate and investigate developmental processes. The courses will be divided into classroom lectures, student presentations and literature reading. Both Dr. Zeng and Dr. Kaplan belong to a variety of educational programs, such as TAHSS (Teachers and High School Students) and BDBS (Building Diversity in Biomedical Sciences). These programs recruit minority or economically disadvantaged students who otherwise may not have the opportunity to be exposed to research. The education aspect of researchplan has been carefully developed to enable students of different levels to perform interdisciplinary research in both laboratories.The proposed research activity will also enhance the infrastructure of the scientific community. First, this work will directly benefit the local community of Tufts University. In particular, it will contribute to the infrastructure of the Tufts Bioengineering and Biotechnology Center. Through its education and training programs, the center connects members within the academia community (students, postdocs and faculty) and between academia and industry. Moreover, the results obtained from this research will be sharedwith other scientists through publications, and in conferences and research seminars throughout the nation. Thus, the activities resulting from this research will have a positive impact on the broad scientific community as well.