Physiologic Loading for Cartilage Tissue Engineering

软骨组织工程的生理负荷

基本信息

批准号：
8126444
负责人：
Clark T. Hung
金额：
$ 72.57万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-01-24 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8126444
关键词：
Address Advocate Algorithms Anatomy Animal Model Animals Area Arthroscopy Biochemical Biological Biomechanics Biomedical Engineering Bioreactors Cadaver Caliber Canis familiaris Cartilage Cells Chemicals Chondrocytes Clinical Competence Computer Simulation Defect Degenerative Disorder Degenerative polyarthritis Development Engineering Environment Exhibits Extracellular Matrix Failure Fostering Future Guidelines Healed Health Human Hydrogels Implant In Situ In Vitro Inferior Knee Laboratories Location Mechanics Missouri Modeling Monitor Operative Surgical Procedures Orthopedics Outcome Performance Physiological Property Publishing Research Research Personnel Serum Site Stimulus Stress Structure Surface Surgeon Swelling System Techniques Testing Thick Tissue Engineering Tissue Grafts Tissues Translating Trauma Universities Validation Weight-Bearing state Work Wound Healing articular cartilage base cartilage repair clinical practice clinically relevant design experience healing implantation improved in vivo in vivo Model injured insight joint loading model development multidisciplinary preconditioning repaired research study scaffold tool

Address Advocate Algorithms Anatomy Animal Model Animals Area Arthroscopy Biochemical Biological Biomechanics Biomedical Engineering Bioreactors Cadaver Caliber Canis familiaris Cartilage Cells Chemicals Chondrocytes Clinical Competence Computer Simulation Defect Degenerative Disorder Degenerative polyarthritis Development Engineering Environment Exhibits Extracellular Matrix Failure Fostering Future Guidelines Healed Health Human Hydrogels Implant In Situ In Vitro Inferior Knee Laboratories Location Mechanics Missouri Modeling Monitor Operative Surgical Procedures Orthopedics Outcome Performance Physiological Property Publishing Research Research Personnel Serum Site Stimulus Stress Structure Surface Surgeon Swelling System Techniques Testing Thick Tissue Engineering Tissue Grafts Tissues Translating Trauma Universities Validation Weight-Bearing state Work Wound Healing articular cartilage base cartilage repair clinical practice clinically relevant design experience healing implantation improved in vivo in vivo Model injured insight joint loading model development multidisciplinary preconditioning repaired research study scaffold tool

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项目摘要

DESCRIPTION (provided by applicant): Articular cartilage exhibits a poor intrinsic healing capacity when injured in trauma or by degenerative diseases such as osteoarthritis (OA). In cartilage tissue engineering, there are two prevailing points of view regarding implantation of engineered constructs in vivo. One approach places the cell-scaffold immediately into the defect site and relies on the in situ biological and loading environment to foster development of the fledgling construct. Another approach is to first cultivate constructs in vitro to permit some elaboration of material properties to minimize the propensity of construct cracking. Advocated by Guilak and co-workers (2000), the concept of Functional Tissue Engineering (FTE) has promoted the use of physiologic loading bioreactor systems to cultivate engineered cartilage tissues to better produce replacement tissues with functional (load- bearing) properties of articular cartilage. While an FTE approach has shown promise in guiding tissue development in culture, the clinical benefits of mechanical preconditioning of engineered constructs for cartilage repair is currently unknown. Tissue repair may be influenced by in vitro loading-induced composition and structure and/or by the act of preconditioning of chondrocytes to a dynamic loading environment prior to introduction in the joint loading milieu. In this competitive renewal two parallel but independent aims, one hypothesis-driven and the other model development-driven, are proposed and address the same fundamental effort to translate our basic tissue engineering studies to animal models and eventually to humans. Specific Aim 1 (hypothesis-driven): To test the hypothesis that mechanical preconditioning improves engineered construct performance, compared to free-swelling (non-loaded) constructs, in the functional repair of full- thickness articular cartilage defects. Apply dynamic deformational loading (DL) or free-swelling (FS) to chondrocyte-seeded hydrogel constructs in serum-free culture. When constructs attain a Young's modulus of 25% and 100% of site-matched native canine articular cartilage, implant constructs into a defect in the canine femoral condyle (high load-bearing) or trochlear groove (moderate load-bearing) and monitor tissue repair (e.g., material properties, biochemical properties, arthroscopy, and lameness scores) over a 1-year period. Specific Aim 2 (model development-driven): To develop a computational biphasic three-dimensional contact model of the canine knee that will provide insights to the engineered construct implantation environment. Perform validation of construct crack initiation in canine cadaver knee loading studies. This model will aid interpretation of the experimental defect repair results (Specific Aim 1) as well as provide general guidance for the requisite material properties of the engineered cartilage construct necessary to survive the in situ loading environment for a focal defect of a particular diameter and anatomical location, and initial material properties. To test our hypotheses and achieve our aims, a multidisciplinary team of investigators from Columbia University and the University of Missouri has been assembled. These studies have been designed with the anticipation that the outcomes of our specific aims will eventually allow us to design experiments to predict in vivo repair performance of engineered tissues. PUBLIC HEALTH RELEVANCE: As the growing promise of engineered cartilage grafts is realized in clinical practice, it will be important to understand the implications that mechanical preconditioning of engineered tissue grafts in culture has on tissue repair and clinical outcome. Moreover, orthopaedic surgeons will need specific guidelines to guide them in reparative strategies using engineered cartilage that may possess tissue properties inferior to the native tissue. A clinically relevant algorithm derived from translational evidence for guiding decisions regarding indications for current and future cartilage repair strategies would be invaluable to surgeons.

描述（由申请人提供）：关节软骨在创伤或因骨关节炎（OA）等退行性疾病受伤时表现出较差的内在愈合能力。在软骨组织工程中，关于体内工程结构的植入有两种流行的观点。一种方法将细胞折磨立即置于缺陷部位，并依靠原位生物学和加载环境来促进刚起步的构建体的发展。另一种方法是首先在体外培养构造，以允许对材料特性进行一些详细说明，以最大程度地减少构造裂纹的倾向。由Guilak及其同事（2000）提倡的功能组织工程（FTE）的概念促进了使用生理负荷生物反应器系统来培养工程软骨组织以更好地生产具有关节软骨的功能性（负载 - 轴承）特性的替代组织。尽管FTE方法在指导培养物中的组织发展方面有希望，但目前尚不清楚工程构建体进行机械预处理的临床优势。组织修复可能会受到体外负荷诱导的组成和结构的影响和/或在引入关节载荷环境之前，将软骨细胞预处理到动态载荷环境之前。在这种竞争性更新中，提出了两个平行但独立的目标，一个假设驱动的和另一个模型发展驱动的目标，并解决了将我们的基本组织工程研究转化为动物模型，并最终转化为人类的基本努力。特定目标1（假设驱动）：在实现全厚度关节软骨缺陷的功能修复中，与自由开放的（未载荷）结构相比，机械预处理改善了工程构造性能的假设。在无血清培养物中，将动态变形载荷（DL）或自由式散布（FS）应用于软骨细胞种子水凝胶构建体。当结构达到年轻的模量为25％和100％的现场犬犬关节软骨时，将植入物构造成股con股（股）股d犬（高负荷）或车辆凹槽（中度负荷）和监测组织修复（例如，材料，材料，过度，高性分子，高含量和lammementies和lamme score score score consemal contyle（高负荷）或行支凹槽（中等负荷）和lamecote score conementies contiments contrial consuctant unters构造。特定目标2（模型开发驱动）：开发犬膝膝膝膝膝次的计算双相三维接触模型，该模型将为工程结构植入环境提供见解。在犬尸体膝盖载荷研究中对构造裂纹启动进行验证。该模型将有助于解释实验缺陷修复结果（特定目的1），并为在原位负载环境中生存的工程软骨结构的必要材料特性提供一般指导，以使特定直径和解剖位置的局灶性缺陷以及初始材料特性。为了检验我们的假设并实现我们的目标，哥伦比亚大学和密苏里大学的一个跨学科调查员团队已经组装。这些研究的设计是，我们的特定目标的结果最终将使我们能够设计实验以预测工程组织的体内维修性能。公共卫生相关性：随着在临床实践中实现了工程软骨移植物的越来越多的希望，重要的是要了解工程组织移植物在培养中的机械预处理对组织修复和临床结果的影响。此外，骨科医生将需要特定的指南，以使用工程软骨来指导他们以较低的组织特性的重复策略来指导他们。从翻译证据中得出的临床相关算法是指导有关当前和未来软骨修复策略指示的决策，这对外科医生来说是无价的。