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Laser Treatment Modality for Strengthening Osteoarthritic Cartilage

强化骨关节炎软骨的激光治疗方式

基本信息

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
项目类别：
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

项目摘要

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.

项目总结