Engineering Lubrication in Tissue Engineered Cartilage

组织工程软骨中的工程润滑

• 批准号: 8163394
• 负责人: Kyriacos A Athanasiou
• 金额: $ 33.93万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8163394
• 关键词: Adult; Affect; Animal Model; Animals; Arthritis; Biochemical; Biological; Biomechanics; Biomedical Engineering; Cartilage; Cartilage Diseases; Cartilage injury; Chondrocytes; Clinical; Collaborations; Degenerative polyarthritis; Engineering; Environment; Friction; Future; Goals; Growth Factor; Head; Healed; Health Care Costs; Homeostasis; Hydrostatic Pressure; Implant; In Vitro; Inflammation; Interdisciplinary Study; Investigation; Joints; Kinetics; Knee; Knowledge; Lead; Lubricants; Lubrication; Measures; Mechanical Stimulation; Mechanics; Mediating; Mission; Modeling; Mus; Natural regeneration; Orthopedic Surgery procedures; Orthopedics; Pain; Pathway interactions; Patients; Phase; Physiology; Production; Property; Protein Biosynthesis; Proteins; Regimen; Regulation; Research Personnel; SCID Mice; Shapes; Signal Pathway; Signal Transduction; Site; Solid; Staging; Surface; Surgeon; System; Therapeutic; Tissue Engineering; Tissues; Translations; Validation; Weight-Bearing state; articular cartilage; bone; design; disability; healing; improved; in vivo; joint mobilization; mRNA Expression; mouse model; protein expression; research study; scaffold; self assembly; shear stress; subcutaneous; success; treatment strategy

DESCRIPTION (provided by applicant): Articular cartilage is a long-lasting, durable tissue that lubricates and redistributes compressive loading in joints. Both of these functions are compromised in cartilage diseases and injuries such as osteoarthritis (OA). A key component of articular cartilage lubrication is superficial zone protein (SZP), which displays altered levels in animal models of early- and late-stage OA. SZP synthesis is mechanically regulated in vivo, and through mechanical stimulation its expression has been manipulated successfully in vitro. Combining these findings with previous successes in manipulating the mechanical properties of engineered cartilage, the long- term mission of the investigators is the complete regeneration of articular cartilage in the joint to restore both the lubrication and mechanical functionality of this tissue. Toward this goal, the hypothesis of this proposal is that cartilage engineered with boundary lubrication and mechanical properties using a combination of growth factors, cytoskeletal modulation, and mechanical signaling can restore articular cartilage in a murine model by maintaining its biological homeostasis and structural integrity. Three specific aims are proposed: 1) to determine the influence and the mechanism of the biomechanical signaling of hydrostatic pressure on SZP mRNA and protein expression in articular cartilage tissue explants, 2) to engineer lubrication into tissue engineered cartilage using a combination of growth factors, cytoskeletal modulation, and mechanical signaling, and 3) to determine the integrity and stability of lubricated, tissue engineered cartilage in vivo utilizing a SCID mouse model. The successful validation of lubricated, tissue engineered construct functionality the mouse model would lead to larger animal studies and potential clinical translation. PUBLIC HEALTH RELEVANCE: By providing a low friction surface and by distributing load, healthy articular cartilage is responsible for the smooth movement of joints. Cartilage injuries and degeneration result in increased friction and shear stresses being applied directly to bone, leading to inflammation, pain, and disability. Degenerative joint disease and osteoarthritis (OA) affects over 26 million adults in the U.S., and health care costs for treatment of OA in the knee alone are $14 billion per year. Uncovering the mechanisms of joint lubrication will aid in the understanding of degenerative joint disease or osteoarthritis. Engineering new cartilage with lubrication and mechanical properties would result in a functional tissue that could potentially be used to treat damaged and arthritic joints.

描述（由申请人提供）：关节软骨是一种持久的耐用组织，可在关节中润滑和重新分布压缩负荷。这两种功能都在软骨疾病和骨关节炎（OA）等伤害中受到损害。关节软骨润滑的关键组成部分是浅层区蛋白（SZP），它显示出早期和晚期OA动物模型中的水平改变。 SZP合成在体内受到机械调节，通过机械刺激，其表达在体外成功地操纵。将这些发现与以前在操纵工程软骨的机械性能方面取得的成功相结合，研究人员的长期任务是关节中关节软骨的完全再生，以恢复该组织的润滑和机械功能。为了实现这一目标，该提案的假设是使用生长因子组合，细胞骨架调制和机械信号传导结合使用边界润滑和机械性能设计的软骨，可以通过维持其生物稳态和结构完整性来恢复鼠模型中的关节软骨。提出了三个具体目的：1）确定液压压力对SZP mRNA的生物力学信号传导和关节软骨组织外植体中蛋白质表达的影响和机制，2）使用生长因子的结合，并确定cytosketical Signaligation ins in in Integrigity in in Insporting and Integrigity in Syfterigation and Integrigation in Synecriatient in toshiste intery intery ofister intery intery of组织工程软骨。使用SCID鼠标模型的体内。润滑，组织工程构建功能的成功验证小鼠模型将导致更大的动物研究和潜在的临床翻译。 公共卫生相关性：通过提供低摩擦表面并通过分配负载，健康关节软骨负责关节的平稳运动。软骨损伤和变性会导致摩擦和剪切应力直接施加到骨骼上，从而导致炎症，疼痛和残疾。退化性关节疾病和骨关节炎（OA）在美国影响超过2600万成年人，仅膝盖治疗OA的医疗保健费用每年为140亿美元。发现关节润滑的机制将有助于理解退化性关节疾病或骨关节炎。具有润滑和机械性能的工程新软骨将导致功能性组织，该组织有可能用于治疗受损和关节的关节。