Collaborative Research: Ligament Tissue Engineering

合作研究：韧带组织工程

• 批准号: 0854149
• 负责人: Aaron Goldstein
• 金额: $ 22.91万
• 依托单位: Virginia Polytechnic Institute and State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0854149&HistoricalAwards=false
• 关键词: Collaborative; Research; Ligament; Tissue; Engineering

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)0854149/0853668Goldstein/HahnThe design of clinically effective materials for the surgical repair of ruptured ligaments remains a challenging biomedical engineering problem. Currently, tissue grafts from the patient and cadaveric sources are the only clinically effective materials for repair, as synthetic materials fatigue under cyclic loading. However, intrinsic limitations with these tissue sources include donor site complications and risk of disease transmission. An alternative approach to form functional ligament tissue - by combining a population of the patient's own adult stem cells with an oriented nanofiber scaffold - has been proposed, but is hindered by three technological constraints: 1) nanofiber scaffolds produced by electrospinning do not have the appropriate shape and size for ligament reconstruction, 2) cells do not migrate into electrospun scaffolds, and 3) adult stem cells do not readily form a robust collagen-rich extracellular matrix (ECM). Therefore, the specific goals of this project are to establish a methodology to process electrospun scaffolds into three-dimensional structures, implement co-electrospinning to facilitate cell penetration into scaffolds, and to employ cyclic uniaxial stretch to enhance deposition of a ligament-like ECM. The novelty of this project is that it seeks to create new technologies that can be used to fabricate engineered ligament tissues.The intellectual merits of this project are three-fold. First, it will establish novel methodologies to process electrospun scaffolds into three dimensional scaffolds, while ensuring cell penetration. Second, it will identify dynamic mechanical stimuli regimens that induce gene expression and the synthesis of ligament ECM proteins. Third, the objectives of this project are fundamental, and the new technologies that will be developed can be applied generally to the engineering of oriented soft tissues (e.g., peripheral nerve, blood vessel, muscle). Thus, successful completion of this project would significantly advance the field of tissue engineering.The broader impacts of this project include the development and implementation of a new K-12 outreach module "Healing Biomaterials" for Virginia Tech summer engineering camps, and the design of a new module for the undergraduate "Tissue Engineering and Drug Delivery" course at Texas A&M University. In addition, the work will be incorporated into the module "Biomimetic Approaches to Tissue Engineering" to be presented annually at the International Workshop and Summer School "Bioinspired Materials: Biomimetic Design and Assembly" in Lugano, Switzerland.

该奖项是根据2009年美国复苏和再投资法案（公法111-5）0854149/0853668 Goldstein/Hahlynn设计的临床有效材料的手术修复断裂韧带仍然是一个具有挑战性的生物医学工程问题。 目前，来自患者和尸体来源的组织移植物是唯一临床有效的修复材料，因为合成材料在循环载荷下会疲劳。 然而，这些组织来源的内在局限性包括供体部位并发症和疾病传播的风险。 已经提出了一种形成功能性韧带组织的替代方法-通过将患者自身的成体干细胞群体与定向的骨基质支架相结合-但受到三个技术限制的阻碍：1）通过静电纺丝产生的支架不具有用于韧带重建的适当形状和尺寸，2）细胞不迁移到静电纺丝支架中，和3）成体干细胞不容易形成强健的富含胶原的细胞外基质（ECM）。 因此，本项目的具体目标是建立一种方法来将静电纺丝支架加工成三维结构，实施共静电纺丝以促进细胞渗透到支架中，并采用循环单轴拉伸来增强韧带样ECM的沉积。 这个项目的新奇在于它试图创造新的技术，可以用来制造工程韧带组织。 首先，它将建立新的方法来将电纺支架加工成三维支架，同时确保细胞渗透。 其次，它将确定动态机械刺激方案，诱导基因表达和韧带ECM蛋白的合成。 第三，本项目的目标是根本性的，并且将开发的新技术可以普遍应用于定向软组织的工程（例如，外周神经、血管、肌肉）。 因此，该项目的成功完成将大大推进组织工程领域，该项目的更广泛的影响包括开发和实施一个新的K-12外展模块“愈合生物材料”的弗吉尼亚理工大学的夏令营工程，并设计了一个新的模块的本科“组织工程和药物输送”课程在德克萨斯州A M大学。 此外，这项工作将被纳入“组织工程的仿生方法”模块，每年在瑞士卢加诺举行的国际研讨会和暑期学校“仿生材料：仿生设计和组装”上发表。