A Translational Approach Towards Ligament Regeneration

韧带再生的转化方法

基本信息

批准号：
8692537
负责人：
CATO T. LAURENCIN
金额：
$ 33.79万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2016-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8692537
关键词：
Address Affect Allografting Anterior Aspirate substance Autologous Autologous Transplantation Biological Biomechanics Biomedical Engineering Biomimetics Bioreactors Bone Marrow Bone Marrow Cells Cell Adhesion Cell physiology Cell-Cell Adhesion Cells Chemicals Clinical Connective Tissue Development Disease Engineering Environment Fiber Goals Growth Healed Immune response In Vitro Knee Ligaments Mechanical Stimulation Mechanics Mesenchymal Stem Cells Methods Modeling Modification Mononuclear Morbidity - disease rate Natural regeneration Operative Surgical Procedures Oryctolagus cuniculus Patients Performance Plasma Pre-Clinical Model Property Role Rupture Site Source Stem cells Structure Supporting Cell Surface Surface Properties System Techniques Tendon structure Tissue Engineering Tissues Translations Vascularization adult stem cell base design efficacy evaluation hamstring healing immunogenic implantation improved in vivo in vivo Model injured insight migration mimicry poly(lactic acid)public health relevance reconstruction repaired response scaffold stem cell biology stem cell technology subcutaneous tissue regeneration translational approach

项目摘要

DESCRIPTION (provided by applicant): The anterior crucial ligament (ACL) is the most commonly injured ligament of the knee. Due to inherently poor healing potential and limited vascularization, ACL ruptures do not heal and surgical replacement is often required. Current treatments include the use of autografts (usually with tissue from the patellar tendon or hamstring tendon) or allografts. The limitations associated with the use of autografts include a second surgery, which may cause donor site morbidity and limited availability. Allografts can potentially transmit disease and elicit an unfavorable immunogenic response from the host. Tissue engineering has emerged as an alternative strategy to overcome the limitations of the biological grafts. Our previous studies have led to the development of a tissue engineered synthetic ACL scaffold mimicking the hierarchical structural complexity and mechanics of natural ligament. Recent advances in stem cell technology have shown great potential of bone marrow derived as well as tissue specific cells in promoting the repair and regeneration of connective tissues due to phenotypic plasticity. The goal of this proposal is to develop a translational approach towards accelerated anterior crucial ligament regeneration by combining biomimetic and biofunctional scaffolds with advances in stem cell biology. Our goal will be achieved through the design and optimization of a cell-seeded, three- dimensional (3D) degradable scaffold with structural, mechanical and biological properties similar to natural ACL. 3D braiding in combination with surface modification techniques will be used to create scaffolds with optimized pore structure and surface properties to facilitate cell adhesion, migration, proliferation, and tissue in- growth, as well as mechanical properties comparable to natural ACL. The cell-scaffold constructs will be optimized for enhanced cellular performance and ligamentogenesis both in vitro and in vivo. Our overall hypothesis is that a cell-seeded, degradable, fibrous scaffold that s biomechanically comparable to natural ACL with appropriate surface properties can encourage and support the accelerated regeneration of a new ACL. The successful development of such tissue-engineered constructs will present an alternative to the currently available options for ACL repair.

描述（由申请人提供）：前关键韧带（ACL）是膝盖最常受伤的韧带。由于固有的愈合潜力较差和血管化有限，ACL 破裂无法愈合，通常需要手术置换。目前的治疗方法包括使用自体移植物（通常使用来自髌腱或腿筋腱的组织）或同种异体移植物。与使用自体移植物相关的限制包括第二次手术，这可能导致供体部位发病和可用性有限。同种异体移植物可能会传播疾病并引起宿主不利的免疫原性反应。组织工程已成为克服生物移植局限性的替代策略。我们之前的研究开发了一种组织工程合成 ACL 支架，模仿天然韧带的层次结构复杂性和力学。干细胞技术的最新进展显示出骨髓来源的细胞以及组织特异性细胞由于表型可塑性而在促进结缔组织修复和再生方面的巨大潜力。该提案的目标是通过将仿生和生物功能支架与干细胞生物学的进步相结合，开发一种加速前关键韧带再生的转化方法。我们的目标将通过设计和优化细胞接种的三维 (3D) 可降解支架来实现，该支架具有与天然 ACL 相似的结构、机械和生物特性。 3D 编织与表面改性技术相结合，将用于创建具有优化的孔结构和表面特性的支架，以促进细胞粘附、迁移、增殖和组织内生长，以及与天然 ACL 相当的机械特性。细胞支架结构将被优化，以增强体外和体内的细胞性能和韧带生成。我们的总体假设是，细胞接种的、可降解的纤维支架在生物力学上与具有适当表面特性的天然 ACL 相当，可以促进和支持新 ACL 的加速再生。这种组织工程结构的成功开发将为目前可用的 ACL 修复方案提供一种替代方案。