Biologic Scaffold Prostheses to Enhance Meniscus Repair

增强半月板修复的生物支架假体

• 批准号: 8838088
• 负责人: Joe Brice Weinberg
• 金额: --
• 依托单位: DURHAM VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8838088
• 关键词: 3-Dimensional; Aging; Biological Markers; Biomechanics; Canis familiaris; Caring; Cartilage; Categories; Cell Differentiation process; Cells; Degenerative polyarthritis; Development; Devices; Diagnosis; Disease; Fiber; Fibrin; Gait abnormality; Gel; Goals; Growth; Growth Factor; Histologic; Hydrogels; Implant; In Vitro; Inflammation; Inflammation Mediators; Injury; Interleukin-1; Joints; Knee; Knee joint; Left; Mechanical Stress; Mechanics; Medial meniscus structure; Mediator of activation protein; Medical; Meniscus structure of joint; Metabolism; Methods; Military Personnel; Mission; Molds; Morbidity - disease rate; Morphology; Musculoskeletal System; Nitric Oxide; Obesity; Orthopedics; Osteoarthrosis Deformans; Pain; Pathologic; Pathology; Patient Care; Performance; Phenotype; Physiological; Play; Production; Property; Prostaglandins; Prosthesis; Public Health; Recovery; Resected; Rheumatoid Arthritis; Role; Secondary to; Serum; Services; Site; Structure; Synovial Fluid; System; Technology; Testing; Time; Tissue Engineering; Tissues; Transforming Growth Factor beta; Trauma; United States; Variant; Veterans; Work; abstracting; articular cartilage; base; bone; bone morphogenetic protein 2; bone morphogenetic protein 6; cytokine; design; design and construction; disability; implantation; in vivo; joint function; joint loading; miniaturize; novel; osteogenic; prevent; repaired; research study; response; scaffold; stem cell technology; tibia; transmission process

Abstract Menisci play critical roles in stabilization and load transmission in the knee joint. Meniscal damage or loss often results in progressive osteoarthritic degeneration of the articular cartilage and other joint tissues, leading to significant pain and disability. We need better methods to repair or replace damaged menisci. However, most tissue engineering approaches for meniscal replacement require significant culture time for the newly formed tissue to develop functional properties that could withstand joint loading. We have demonstrated the usefulness of three dimensional (3-D) woven scaffolds for tissue engineering purposes. These scaffolds provide physiologic mechanical properties prior to implantation. We have also shown that mechanical stress and cytokines alter the metabolism of menisci and inhibit repair of meniscal injury. The overall goal of our study is to develop a new 3-D composite scaffold for use in the functional tissue engineering of the meniscus. A special advantage of 3-D weaving is that constructs can be designed and built with predetermined control of site-dependent variations in mechanical properties. Also, certain growth factors that may enhance meniscus-bone molding and annealing can be incorporated into the matrix. We will develop the device and also determine effects of soluble mediators such as cytokines, nitric oxide (NO), and prostaglandins (PG) on development, integrity, and function of the prostheses. We will accomplish 4 aims. Aim 1. Design and construct 3-D woven composite scaffolds for use in the functional tissue engineering of the knee meniscus. We will develop a composite scaffold that promotes meniscal fibrochondrocyte development and tissue organization, while effectively replicating the structural and functional mechanical properties of a natural meniscus. Aim 2: Incorporate bioactive factors into the 3-D matrix that will allow fibrochondrocyte differentiation and attachment to bone. We will incorporate growth factors into the materials used in Aim 1 to construct the 3-D woven composite scaffolds. Aim 3: Perform mechanical testing of the composite scaffolds to assess their potential in vitro functionality. Tension, compression, and shear testing will be used to evaluate the critical biomechanical parameters of the developed scaffolds and resulting neomeniscus. We will assess the importance of certain cytokines, growth factors, and other natural mediators such as NO and PG on the development and biomechanical properties of the meniscus prostheses. Aim 4: Test the ability of the meniscus scaffold prosthesis to attach to bone and function in vivo. We will place the in vitro-generated meniscus prostheses into sites of fresh-ly resected medial menisci in dogs and leave the prostheses in place for up to 12 weeks, after which we will evaluate their function and their effects on development of pathology in the joint. Our work will have a direct effect on veterans with meniscal injuries, facilitating a more rapid recovery and reducing long term morbidity. Also, for active-duty military personnel, it may result in more rapid return to active duty.

摘要 半月板在膝关节的稳定和载荷传递中起着关键作用。半月板损伤或丢失 经常导致关节软骨和其它关节组织的进行性骨关节炎变性， 导致严重的疼痛和残疾。我们需要更好的方法来修复或更换受损的神经节。 然而，大多数用于椎间盘置换的组织工程方法需要大量的培养时间， 新形成的组织发展能够承受关节负荷的功能特性。我们有 证实了三维（3-D）编织支架用于组织工程目的的有用性。 这些支架在植入前提供生理机械性能。我们还表明， 机械应力和细胞因子改变了骨水泥的代谢并抑制骨水泥损伤的修复。的 我们研究的总体目标是开发一种新的用于功能组织的三维复合支架 弯月面工程三维编织的一个特殊优点是，可以设计结构， 通过对机械性能中的位置依赖性变化的预定控制来构建。此外，某些 可将可增强髋臼-骨成型和退火的生长因子掺入 矩阵我们将开发该设备，并确定可溶性介质，如细胞因子， 一氧化氮（NO）和前列腺素（PG）对假体的发育、完整性和功能的影响。我们 将实现四个目标。目标1.设计和构建用于在组织工程中使用的3-D编织复合材料支架。 膝关节半月板的功能性组织工程。我们将开发一种复合支架， 骨纤维软骨细胞发育和组织组织，同时有效地复制结构 和自然半月板的功能性机械性能。目的2：将生物活性因子纳入 三维矩阵，将允许纤维软骨细胞分化和附着到骨。我们将合并 在目标1中使用的材料中添加生长因子以构建3D编织复合支架。目标3： 对复合支架进行机械测试，以评估其潜在的体外功能。 拉伸、压缩和剪切试验将用于评价 所开发的支架和由此产生的新半月板。我们将评估某些细胞因子的重要性， 生长因子和其他天然介质如NO和PG对发育和生物力学的影响 半月板假体的性能。目的4：测试半月板支架假体的能力， 附着在骨骼上并在体内发挥作用。我们将把体外生成的半月板假体放置在 新鲜切除的狗内侧韧带，并将假体留在原位长达12周，之后， 我们将评估它们的功能及其对关节病理学发展的影响。我们的工作将 直接影响退伍军人与踝关节受伤，促进更快的恢复和减少长期 发病率此外，对于现役军人来说，这可能会导致更快地恢复现役。