A Translational Approach Towards Ligament Regeneration

韧带再生的转化方法

基本信息

批准号：
8579558
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 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8579558
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

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

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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）是膝盖最常见的韧带。由于固有的愈合潜力和有限的血管化，因此经常需要ACL破裂，并且经常需要手术置换。当前的治疗方法包括使用自体移植（通常与pat肌肌腱或腿筋肌腱的组织）或同种异体移植物。与自体移植有关的局限性包括第二次手术，这可能导致供体部位的发病率和有限的可用性。同种异体移植物可以潜在地传播疾病，并引起宿主的不利免疫反应。组织工程已成为克服生物移植物局限性的替代策略。我们以前的研究导致了组织工程的合成ACL支架的发展，模仿了天然韧带的分层结构复杂性和力学。干细胞技术的最新进展表明，由于表型可塑性而导致结缔组织的修复和结缔组织的修复和再生。该提案的目的是通过将仿生和生物功能的支架与干细胞生物学的进步相结合，开发一种转化方法来加速至关重要的韧带再生。我们的目标将通过设计和优化，具有与天然ACL相似的结构，机械和生物学特性的细胞种子，三维（3D）可降解支架。 3D编织与表面修饰技术结合使用，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，增殖和组织的生长以及与天然ACL相当的机械性能。细胞菌件构建体将在体外和体内优化，以增强细胞性能和韧带生成。我们的总体假设是，具有适当表面特性的天然ACL可以在生物力学上与天然ACL相提并论，可以鼓励和支持新ACL的加速再生。此类组织工程结构的成功开发将为ACL维修的当前可用选择提供替代方案。