Muscle Cell-Enhanced Cartilage Tissue Engineering

描述（由申请人提供）：关节炎是美国残疾的主要原因。尽管它在我们日益老龄化的社会中流行，但关节炎的有效治疗选择仍然有限。关节炎是由关节软骨的破坏引起的，伴随着炎症和疼痛。软骨组织工程为软骨再生和组织功能恢复提供了一个有前途的解决方案。然而，促炎细胞因子在宿主部位的存在不可避免地导致基质降解，导致工程化软骨不稳定。因此，对于临床应用的这种技术，迫切需要工程化稳定的软骨，其对促炎性精氨酸诱导的降解具有抗性。 我们的长期目标是获得软骨调控的关键知识，并提高软骨组织工程技术的临床应用。我们正在开发一种新的策略，将发育生物学的概念和方法与组织工程相结合。在胚胎发生期间，肌肉是与假定的软骨组织一起发育的组织之一。我们广泛的初步研究表明，肌肉细胞在调节软骨稳态和炎症刺激中的作用。我们的中心假设是，肌肉细胞和最佳支架选择可用于通过增强软骨基质产生和对促炎细胞因子的抵抗来增强工程化软骨的稳定性。我们计划通过将原代人关节软骨细胞和间充质干细胞接种在3D蚕丝支架中来验证这一假设。我们计划：1）研究肌细胞在调节软骨基质产生中的作用，2）研究肌细胞在调节对促炎细胞因子的反应中的作用，和3）研究支架材料对肌细胞调节软骨基质产生和对促炎细胞因子的反应的影响。 我们的研究团队由发育生物学、组织工程、免疫学和骨科领域的专家组成。我们相信，我们的协同努力和跨学科的方法将导致更深入地了解软骨稳态的调节和对促炎刺激的反应，为建模和治疗关节炎提供基础知识。因此，我们的研究渴望满足改善组织工程技术的关键需求，并可能导致开发一种新的策略来工程化稳定的软骨用于临床应用。 公共卫生相关性：以炎症和关节破坏为特征的关节炎是我们日益老龄化的社会中残疾的主要原因。然而，这种流行疾病的有效治疗选择仍然有限。我们提出了一种新的策略，通过利用肌肉细胞来设计稳定的软骨组织，以抵抗炎症。因此，我们的研究旨在满足改善软骨再生和关节修复技术的迫切需求，这最终可能成为关节炎的有效治疗方法。

DESCRIPTION (provided by applicant): Arthritis is a leading cause of disability in the United States. Despite its prevalence in our ever-aging society, effective treatment options for arthritis are still limited. Arthritis is caused by the destruction of joint cartilage, which is accompanied by inflammation and pain. Cartilage tissue engineering offers a promising solution to regenerate cartilage and restore tissue function. However, the presence of pro-inflammatory cytokines at the host site inevitably leads to matrix degradation, causing the engineered cartilage to be unstable. Therefore, for this technology to be applied clinically there is a critical need to engineer stable cartilage that is resistant to pro-inflammatory cytokine-induced degradation. Our long-term goal is to gain critical knowledge of cartilage regulation and enhance the technology of cartilage tissue engineering for clinical applications. We are developing a novel strategy that integrates concepts and approaches from developmental biology with those of tissue engineering. During embryogenesis, muscle is one of the tissues that develop alongside the presumptive cartilage tissue. Our extensive preliminary studies indicate a role of muscle cells in regulating cartilage homeostasis and inflammatory stimuli. Our central hypothesis is that muscle cells and optimal scaffold selection can be used to enhance the stability of engineered cartilage by enhancing cartilage matrix production and the resistance to pro-inflammatory cytokines. We plan to test this hypothesis by using primary human articular chondrocytes and mesenchymal stem cells seeded in 3D silk scaffolds. We plan to: 1) investigate the role of muscle cells in regulating cartilage matrix production, 2) investigate the role of muscle cells in regulating the response to pro-inflammatory cytokines, and 3) investigate the effect of scaffold material on muscle cell regulation of cartilage matrix production and the response to pro-inflammatory cytokines. Our research team consists of experts in the fields of developmental biology, tissue engineering, immunology and orthopaedics. We believe that our synergistic efforts and interdisciplinary approach will result in deeper understanding of the regulation of cartilage homeostasis and the response to pro- inflammatory stimuli, providing the fundamental knowledge for modeling and treating arthritis. Thus, our study aspires to meet the critical need of improving tissue engineering technology, and may lead to the development of a novel strategy to engineer stable cartilage for clinical applications. PUBLIC HEALTH RELEVANCE: Arthritis, characterized by inflammation and joint destruction, is a leading cause of disability in our ever-aging society. However, effective treatment options for this prevailing disease still remain limited. We propose a novel strategy to engineer stable cartilage tissue that is resistant to inflammation by utilizing muscle cells. Thus, our research aspires to meet the critical need for improving cartilage regeneration and joint repair technology, which may ultimately be developed as an effective treatment method for arthritis.