Arthroscopic Raman Monitoring of Cartilage Content for PTOA Diagnosis and Chondroregenerative Treatment Response

关节镜拉曼监测软骨含量用于 PTOA 诊断和软骨再生治疗反应

基本信息

批准号：
10675759
负责人：
Michael B Albro
金额：
$ 50.27万
依托单位：
BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-02 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10675759
关键词：
Amides Animals Anisotropy Arthroscopy Autopsy Biochemical Biochemistry Biological Markers Biological Models Biopsy Bioreactors Carboxylic Acids Cartilage Chronic Clinic Clinical Clinical Trials Coculture Techniques Collagen Computer software Contusions Development Diagnosis Disease Effectiveness Engineering Evaluation Extracellular Matrix Fingerprint Functional disorder GAG Gene Health Histopathologic Grade Human Hyaline Cartilage Hydroxyl Radical Image In Vitro Individual Inflammation Inflammatory Injury Intervention Investigation Joints Lasers Least-Squares Analysis Lesion Light Magnetic Resonance Imaging Measurement Measures Mechanics Medical Methods Modeling Molecular Monitor Morphology Natural regeneration Operative Surgical Procedures Optical Biopsy Optics Organ Culture Techniques Outcome Patients Performance Pharmaceutical Preparations Pharmacotherapy Photons Physiological Polymers Property Raman Spectrum Analysis Reader Reconstructive Surgical Procedures Regression Analysis Replacement Arthroplasty Residual state Sample Size Sheep Site Specimen Standardization Stifle joint Structure Sulfate Surface Synovial Membrane System Techniques Technology Testing Time Tissue Engineering Tissues Translations Trauma Traumatic Arthropathy Traumatic injury Visualization Water articular cartilage cartilage degradation cartilage regeneration cartilage repair cartilage transplantation chondroprotection clinical diagnostics clinical practice cohort cytokine deep learning diagnostic biomarker diagnostic platform effectiveness evaluation efficacy evaluation evidence base experience image guided improved in vivo in vivo imaging innovation instrumentation joint function joint injury lens light scattering model development next generation novel pre-clinical preservation preventive intervention randomized, clinical trials repaired response response to injury tissue culture tissue regeneration tissue repair tool treatment research treatment response

项目摘要

Arthroscopic Raman Monitoring of Cartilage Content for PTOA Diagnosis and Chondroregenerative Treatment Response PTOA is a common, incapacitating, chronic condition among individuals who sustain traumatic joint injuries. Currently, even after “successful” surgical reconstruction of the trauma-induced pathoanatomy, supplemented with chondroregenerative interventions, cartilage degeneration continues to progress. Therapies to improve PTOA clinical outcomes are being developed, including chondroprotective disease modifying drugs that mitigate or reverse degeneration of cartilage lesions and chondroregenerative tissue engineering platforms that better recapitulate the composition and structure of healthy hyaline cartilage. However, the ability to assess the efficacy of PTOA treatments that preserve and/or regenerate cartilage is burdened by a lack of standardized diagnostic biomarkers that can objectively evaluate the efficacy of PTOA treatments. For clinical diagnostics, arthroscopic- based macroscopic cartilage grading systems (Outerbridge, ICRS) and MRI portrayals of cartilage composition are, at best, only moderately correlated with quantitative assessments of cartilage composition and material properties relevant to the mechanical integrity and functional performance of the regenerate tissue. Raman spectroscopy is an inelastic light scattering technique that reflects individual molecular vibrational bonds, corresponding to specific biochemical building blocks of key cartilage constituents: GAG, collagen, and water. We propose developing a comprehensive Raman platform for monitoring cartilage compositional biomarkers over the hierarchy of model systems employed for cartilage treatment research, including: 1) a clinical Raman- based arthroscopic probe that achieves real-time analysis of cartilage in in vivo animal studies and patient clinical trials, and 2) a tissue-culture compatible Raman-spectroscopy-interfaced plate reader for the rapid, non- destructive, repeated-measure analysis of live cartilage explants ex vivo. We hypothesize that derived Raman biomarkers can predict the composition, morphology, and material properties of cartilage in response to chondroprotective and/or chondroregenerative treatments more accurately than MRI and arthroscopic-based macroscopic cartilage grading systems (Outerbridge, ICRS). We examine this hypothesis over the hierarchy of PTOA therapy-development model systems including in vitro systems—Ovine cartilage explants subjected to injury and treatment with chondroprotective drugs, engineered cartilage grafts subjected to physiologic + supra- physiologic loading  inflammatory cytokines, and human cartilage explants from autopsy and arthroplasty donors—and an in vivo system-- an ovine stifle joint subjected to PTOA injury, surgical repair, and drug treatments. Through objective assessments of the efficacy of emerging cartilage therapies over the hierarchy of R+D model systems—ex vivo, in vivo, clinical—Raman spectroscopy assessments can advance the next generation of PTOA interventions into the clinic. The translation of Raman-based arthroscopy into a safe, effective medical platform can be transformative for clinical practice, enabling rapid and efficient identification of PTOA cartilage lesions and monitoring of neocartilage regeneration during routine arthroscopy.

关节镜的拉曼监测软骨含量用于PTOA诊断和软骨增生治疗反应 PTOA是维持创伤性关节损伤的个体中常见，无能为力的慢性病。目前，即使在创伤引起的病原体的“成功”手术重建后，随着软骨增长的干预措施，软骨变性继续进行。改进的疗法正在开发PTOA临床结果，包括减轻缓解药物的软骨保护疾病或软骨病变和软骨生成组织工程平台的反向变性概括健康透明软骨的组成和结构。但是，评估效率的能力由于缺乏标准化的诊断，保存和/或再生软骨保存和/或再生软骨的PTOA治疗可以客观地评估PTOA治疗有效性的生物标志物。对于临床诊断，关节镜 - 基于宏观软骨分级系统（Outerbridge，ICR）和软骨组成的MRI刻画充其量仅与软骨组成和材料的定量评估相关与再生组织的机械完整性和功能性能相关的特性。拉曼光谱法是一种无弹性散射技术，反映了个体的分子振动键，对应于特定的生物化学构建基块，构成：堵嘴，胶原蛋白和水。我们建议开发一个全面的拉曼平台，以监视软骨复合生物标志物在软骨治疗研究的模型系统的层次结构上，包括：1）临床拉曼 - 基于关节镜探测器在体内动物研究和患者临床中实现软骨的实时分析试验和2）兼容拉曼 - 谱透镜读板读取器的组织文化，以快速，非 - 现场活软骨的破坏性，重复测量分析。我们假设那个衍生的拉曼生物标志物可以预测软骨的组成，形态和物质特性。比MRI和基于关节镜的，软骨保护和/或软骨增生治疗更准确宏观软骨分级系统（Outerbridge，ICRS）。我们研究了有关层次结构的这一假设 PTOA疗法开发模型系统，包括体外系统 - 抗原软骨外植体用软骨保护药物的损伤和治疗，经过生理 +上的工程软骨移植物生理负荷炎症细胞因子以及尸检和关节置换术的人体软骨外植体供体 - 一个体内系统 - 受PTOA损伤，手术修复和药物的卵子窒息关节治疗。通过客观评估新兴软骨疗法的效率 R+D模型系统 - Ex Vivo，体内，临床 - Raman光谱评估可以推进下一个 PTOA干预措施进入诊所。将基于拉曼的关节镜翻译成安全的有效的医疗平台可以对临床实践进行变革，从而快速有效地识别常规射击过程中的PTOA软骨病变和对新生儿病再生的监测。