Laser Treatment Modality for Strengthening Osteoarthritic Cartilage

强化骨关节炎软骨的激光治疗方式

• 批准号: 10321592
• 负责人: GERARD A. ATESHIAN
• 金额: $ 27.72万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-10 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10321592
• 关键词: Ablation; Activities of Daily Living; Age; American; Animals; Back; Biological; Biomechanics; Biomedical Engineering; Bovine Cartilage; Cartilage; Cartilage Diseases; Cattle; Cell Survival; Chemical Agents; Chondrocytes; Clinical; Collagen; Data; Debridement; Defect; Degenerative Disorder; Degenerative polyarthritis; Development; Disease; Disease Progression; Effectiveness; Ensure; Exhibits; Extracellular Matrix; Female; Fiber Optics; Friction; Future; Health; Hip Osteoarthritis; Homeostasis; Hour; Human; Hydration status; Implant; In Situ; In Vitro; Individual; Joints; Knee Osteoarthritis; Lasers; Longevity; Mainstreaming; Methodology; Modality; Modification; Modulus; Morphology; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Nude Mice; Operative Surgical Procedures; Optics; Organ; Pain; Pathologic; Patient-Focused Outcomes; Plasma; Property; Proteins; Protocols documentation; Reactive Oxygen Species; Replacement Arthroplasty; Research; Research Project Grants; Resistance; Safety; Shock; Side; Surface; Synovial Fluid; System; Technology; Testing; Thermal Ablation Therapy; Thick; Tissue Viability; Tissues; Translating; Visual; Water; Weight-Bearing state; Work; articular cartilage; base; bone; clinically relevant; crosslink; density; design; effectiveness evaluation; human male; improved; in vivo; ionization; irradiation; joint function; male; mechanical properties; novel; pre-clinical; programs; repaired; response; safety assessment; subchondral bone; tool

Project Summary Osteoarthritis (OA) is a debilitating degenerative disease that afflicts an estimated 27 million Americans age 25 and older. This disease leads to the progressive degradation of the articular layers of diarthrodial joints, significantly compromising the main function of cartilage as a load bearing material, leading to pain and limiting activities of daily living. To this day, there are very limited treatment options for slowing down the progression of OA in its early stages. Most therapies, such as highly invasive partial and total joint replacement surgeries are performed at the late stage of the disease. Introducing treatment options to earlier stages of OA presents the potential to retard or slow down disease progression and thus significantly improve patient outcomes. The primary function of articular cartilage is to transmit loads across the joint surfaces while simultaneously minimizing friction and wear. This application describes the development of an ultrafast laser-based treatment tool which has the ability to induce crosslinks into the cartilage collagen network without the addition of a chemical agent, while simultaneously avoiding damaging effects of optical breakdown and ablation. Preliminary data show that laser-induced crosslinks increase compressive stiffness and wear resistance, without compromising cell viability, which may be expected to slow down progression of OA. The overall aim of this application is to develop a range of effective and safe laser operating parameters that enhance cartilage mechanical properties and wear resistance, enabling us to produce a clinically relevant protocol. We also aim to assess the influence of laser-induced short-lived bursts of reactive oxygen species onto the long-term response of cartilage during in vitro and in vivo culture. To translate this technology to future animal and human studies, we will develop and test a laser-based clinical tool for arthroscopic treatment of cartilage in situ. In specific aim 1, we will optimize a framework for structural, morphological and functional modification of the cartilage extracellular matrix subject to femtosecond laser irradiation, using devitalized bovine and human OA cartilage explants. In specific aim 2, we will narrow this range of operating parameters by testing short-term and long-term viability of laser-treated live bovine and human OA (male & female) cartilage explants against untreated controls, using in vitro culture up to 4 weeks. In specific aim 3, we will verify that laser-treated live human OA cartilage explants exhibit comparable viability and health as untreated controls when implanted for up to 8 weeks in the back of nude mice. We will also fabricate a fiber optic-based laser system and validate its effectiveness in simulated in situ arthroscopic applications in OA knee joints. Upon completion of these studies, we will have established effective and safe operating parameters for this novel laser treatment modality, and created a practical tool to test this methodology in situ, first in large animals, then in humans.

项目概要 骨关节炎 (OA) 是一种使人衰弱的退行性疾病，估计有 2700 万 25 岁美国人受到影响 和年纪大了。这种疾病导致关节关节的关节层进行性退化， 严重损害软骨作为承载材料的主要功能，导致疼痛和限制 日常生活活动。迄今为止，减缓病情进展的治疗选择非常有限 OA 还处于早期阶段。大多数疗法，例如高侵入性部分和全关节置换手术 是在疾病晚期进行的。向 OA 早期阶段介绍治疗方案 延缓或减缓疾病进展的潜力，从而显着改善患者的治疗结果。这 关节软骨的主要功能是在关节表面传递载荷，同时 最大限度地减少摩擦和磨损。该应用描述了基于超快激光的治疗的开发 该工具能够诱导软骨胶原蛋白网络交联，而无需添加 化学剂，同时避免光学击穿和烧蚀的破坏性影响。初步的 数据表明，激光诱导交联可提高抗压刚度和耐磨性，且无需 损害细胞活力，这可能会减缓 OA 的进展。此次活动的总体目标是 应用程序是开发一系列有效且安全的激光操作参数，以增强软骨 机械性能和耐磨性，使我们能够制定临床相关的方案。我们也瞄准 评估激光诱导的活性氧的短寿命爆发对长期的影响 体外和体内培养期间软骨的反应。将这项技术转化为未来的动物和 人体研究，我们将开发和测试基于激光的临床工具，用于关节镜软骨治疗 现场。在具体目标1中，我们将优化结构、形态和功能修饰的框架 使用失活的牛和人，对软骨细胞外基质进行飞秒激光照射 OA 软骨外植体。在具体目标 2 中，我们将通过测试短期来缩小操作参数范围 激光处理的活牛和人类 OA（男性和女性）软骨外植体的长期活力 未经处理的对照，使用体外培养长达 4 周。在具体目标 3 中，我们将验证激光处理的活体 人类 OA 软骨外植体在植入后表现出与未经处理的对照相当的活力和健康状况 在裸鼠背部长达8周。我们还将制造基于光纤的激光系统并验证其 模拟原位关节镜在 OA 膝关节中应用的有效性。完成这些后 研究，我们将为这种新型激光治疗建立有效且安全的操作参数 模态，并创建了一个实用工具来现场测试这种方法，首先在大型动物中，然后在人类中。