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

• 批准号: 10503641
• 负责人: Michael B Albro
• 金额: $ 58.4万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 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/10503641
• 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; Degenerative polyarthritis; 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; Randomized Clinical Trials; Reader; Regression Analysis; Replacement Arthroplasty; Residual state; Sample Size; Sheep; Site; Specimen; Standardization; Stifle joint; Structure; Sulfate; Surface; Synovial Membrane; System; Techniques; Testing; Time; Tissue Engineering; Tissues; Translations; Trauma; Traumatic injury; Visualization; Water; articular cartilage; base; cartilage degradation; cartilage transplantation; 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; reconstruction; repaired; response; response to injury; tissue culture; tissue regeneration; tissue repair; tool; treatment research; treatment response; vibration

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.

关节镜下拉曼检测软骨中软骨素含量用于PTOA诊断和软骨再生 治疗反应 PTOA是一种常见的，失能的，慢性疾病的个人谁遭受创伤性关节损伤。 目前，即使在“成功”的创伤引起的病理解剖手术重建，补充 通过软骨再生干预，软骨退化继续发展。改善疗法 PTOA临床结果正在开发中，包括软骨保护性疾病修饰药物， 或逆转软骨病变的退化和软骨再生组织工程平台， 概括健康透明软骨的组成和结构。然而，评估疗效的能力 保留和/或再生软骨的PTOA治疗的负担是缺乏标准化的诊断， 生物标志物，可以客观地评估PTOA治疗的疗效。对于临床诊断，关节镜检查- 基于宏观软骨分级系统（Outerbridge，ICRS）和软骨组成的MRI描述 最多只能与软骨成分和材料的定量评估适度相关 与再生组织的机械完整性和功能性能相关的性质。拉曼 光谱学是一种反射单个分子振动键的非弹性光散射技术， 对应于关键软骨成分的特定生物化学构建块：GAG、胶原蛋白和水。 我们建议开发一个全面的拉曼平台，用于监测软骨成分生物标志物 在用于软骨治疗研究的模型系统的层级上，包括：1）临床拉曼- 基于关节镜探头，可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）组织培养兼容的拉曼光谱接口板读数器，用于快速，非 离体活软骨外植体的破坏性重复测量分析。我们假设推导出的拉曼光谱 生物标志物可以预测软骨的组成、形态和材料特性， 软骨保护和/或软骨再生治疗比基于MRI和关节镜的治疗更准确 宏观软骨分级系统（Outerbridge，ICRS）。我们检查这个假设的层次结构， PTOA治疗-发育模型系统，包括体外系统-接受PTOA治疗的绵羊软骨外植体 损伤和用软骨保护药物治疗，经过生理+超- 生理负荷导致炎性细胞因子和来自尸检和关节成形术的人软骨外植体 供体和体内系统--羊后膝关节PTOA损伤、手术修复和药物治疗 治疗。通过客观评估新兴软骨疗法的疗效， 研发模型系统-离体、体内、临床-拉曼光谱评估可以推动下一个 将PTOA干预措施引入临床。将基于拉曼的关节镜手术转化为安全， 有效的医疗平台可以为临床实践带来变革，能够快速有效地识别 常规关节镜检查中PTOA软骨损伤和新软骨再生的监测。