Laser Treatment Modality for Strengthening Osteoarthritic Cartilage

项目摘要 骨关节炎(OA)是一种衰弱的退行性疾病，估计有2700万25岁的美国人患有这种疾病。 而且年纪也更大。这种疾病导致腹股沟关节的关节层进行性退化， 严重损害作为承重材料的软骨的主要功能，导致疼痛和限制 日常生活活动。到目前为止，延缓病情发展的治疗选择非常有限。 办公自动化的早期阶段。大多数治疗方法，如高度侵入性的部分和全部关节置换手术 都是在疾病晚期进行的。向早期骨性关节炎患者介绍治疗方案 有可能延缓或减缓疾病的进展，从而显著改善患者的预后。这个 关节软骨的主要功能是同时在关节表面传递载荷 最大限度地减少摩擦和磨损。本申请描述了一种基于超快激光的治疗方法的发展 该工具能够诱导交联剂进入软骨胶原网络，而不需要添加 化学试剂，同时避免光学击穿和烧蚀的破坏性影响。初步 数据表明，激光诱导的交联会增加压缩硬度和耐磨性，而不是 细胞活性受损，可能会减缓骨性关节炎的进展。这样做的总体目标是 应用是开发一系列有效和安全的激光操作参数，以增强软骨 机械性能和耐磨性，使我们能够生产出临床相关的方案。我们还瞄准了 评估激光诱导的短暂的活性氧爆发对长期的影响 软骨在体外和体内培养过程中的反应。将这项技术转化为未来的动物和 在人体研究中，我们将开发和测试一种基于激光的临床工具，用于关节镜下的软骨治疗 SITE。在具体目标1中，我们将优化结构、形态和功能修饰的框架 灭活牛和人经飞秒激光照射后的软骨细胞外基质 骨性关节炎软骨移植。在具体目标2中，我们将通过测试短期运行参数来缩小这一范围 激光处理的活牛和人骨关节炎(男性和女性)软骨移植的长期生存能力 未经处理的对照组，采用体外培养，最长达4周。在具体目标3中，我们将验证激光治疗的活体 人骨关节炎软骨移植的活性和健康状况与未经处理的对照组相当 在裸鼠背部最多8周。我们还将制作一个基于光纤的激光系统，并验证其 模拟关节镜在膝关节骨性关节炎中的应用效果。在完成这些任务后 通过研究，我们将为这种新型的激光治疗建立有效和安全的操作参数 并创造了一种实用的工具来在现场测试这一方法，首先在大型动物中，然后在人类中。

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.