Molecular engineering of HA-based lubricants for articular cartilage

用于关节软骨的 HA 基润滑剂的分子工程

• 批准号: 10712721
• 负责人: Shyni Varghese
• 金额: $ 61.19万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-21 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10712721
• 关键词: Acute; Adhesions; Adhesives; Animal Model; Architecture; Atomic Force Microscopy; Bone Tissue; Cartilage; Cartilage injury; Charge; Clinic; Clinical; Degenerative polyarthritis; Deterioration; Development; Electrostatics; Engineering; Ensure; Exhibits; Extracellular Matrix; Family suidae; Formulation; Friction; Goals; Histologic; Hyaluronic Acid; Image; Individual; Injury; Intervention; Intra-Articular Injections; Joints; Liquid substance; Lubricants; Lubrication; Lysine; Measurement; Mechanics; Modeling; Molecular; Molecular Weight; Monitor; Movement; Operative Surgical Procedures; Outcome; Pain; Property; Pyrimidinones; Research; Role; Saline; Slide; Surface; Synovial Fluid; Synovial Membrane; Time; Tissues; Trauma; Traumatic Arthropathy; United States; Weight-Bearing state; anterior cruciate ligament injury; anterior cruciate ligament reconstruction; articular cartilage; cartilage degradation; chondroprotection; design; healing; improved; improved outcome; in vivo; inflammatory marker; joint injury; lubricin; novel; novel therapeutic intervention; prevent; repaired; success

ABSTRACT Altered lubrication of articular cartilage following joint injury increases friction between the sliding cartilage surfaces, leads to deterioration of cartilage, and hastens the development of osteoarthritis (OA). OA due to joint injury, termed as post-traumatic osteoarthritis (PTOA), is estimated to account for at least 12% of all OA cases in the United States and approximately half of the individuals with an anterior cruciate ligament (ACL) injury develop PTOA regardless of the ACL reconstruction. Replenishing the synovial fluid and thereby restoring the articular cartilage lubrication has been demonstrated to benefit the joint. The overarching goal of the proposed study is to investigate the potential of cartilage-adhering, self-healing hyaluronic acid molecules to prevent or delay the degeneration of articular cartilage, and thereby osteoarthritis, following injury or trauma. The molecularly engineered HA-based lubricants are designed to integrate the function of both hyaluronic acid and lubricin, two key components of the synovial fluid, while exhibiting self-repairing ability. The self-healing properties are incorporated to ensure both long-term retention and adaptability of the lubricant within the mechanically active joint, while the cartilage adhering properties are expected to improve boundary lubrication. We hypothesize that the dynamic cartilage-adhering molecules that integrate the molecular features of HA and lubricin and simultaneously exhibit self-healing properties will protect the articular cartilage and prevent or slow down the progression of PTOA. Towards this, we will: (i) develop cartilage-adhering, self-healing HA molecules and determine the effect of molecular architecture-lubrication function relationship, (ii) determine the effect of the molecular architecture of the proposed novel HA-based lubricants on chondroprotection by using a joint-on-chip platform, and (iii) determine the effect of these lubricants on mitigating the development of post-traumatic osteoarthrits. The proposed studies will enable a new paradigm in which intra-articular injection of self-healing HA-bottle brush molecules could be an important treatment following acute injury to ameliorate or delay PTOA, or they could be used as an adjunct after surgical repair to improve the outcome.

抽象的 关节损伤后关节软骨的润滑改变会增加滑动软骨之间的摩擦 表面，导致软骨恶化，并加快骨关节炎（OA）的发展。 OA由于关节 据估计，受伤被称为创伤后骨关节炎（PTOA），估计占所有OA病例的12％ 在美国和大约一半的患有前交叉韧带（ACL）损伤的个体 开发PTOA，无论ACL重建如何。补充滑液，从而恢复 已证明关节软骨润滑有益于关节。拟议的总体目标 研究是为了研究软骨粘附的自我修复透明质酸分子的潜力，以预防或 受伤或创伤后，延迟关节软骨的变性，从而延迟骨关节炎。这 分子设计的基于HA的润滑剂旨在整合透明质酸和 润滑剂是滑液的两个关键成分，同时表现出自我修复能力。自我修复 合并性能以确保润滑剂在 机械活动的关节，而软骨粘附特性则有望改善边界润滑。 我们假设动态软骨粘附的分子整合了HA和HA的分子特征 润滑剂和同时表现出自我修复特性将保护关节软骨并预防或缓慢 向下PTOA的进展。在此方面，我们将：（i）发展软骨粘附的，自我修复的HA分子 并确定分子结构润滑功能关系的影响，（ii）确定 拟议的新型基于HA的润滑剂的分子结构是在软骨保护方面，通过使用片上的关节芯片 平台和（iii）确定这些润滑剂对缓解创伤后发展的影响 骨关节炎。拟议的研究将实现一个新的范式，其中关节内注射自我修复 HA瓶刷分子可能是急性损伤以改善或延迟PTOA后的重要治疗方法， 否则它们可以在手术修复后用作辅助手段以改善结果。