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

关节镜下拉曼监测软骨含量在PTOA诊断和软骨再生中的应用 治疗反应 在遭受创伤性关节损伤的个体中，PTOA是一种常见的、使人丧失能力的慢性疾病。 目前，即使在成功的手术重建后的创伤诱导的病理解剖，补充 随着软骨再生的干预，软骨退变继续进展。需要改进的治疗方法 PTOA的临床结果正在制定中，包括减轻软骨保护性疾病的药物 或逆转软骨退变病变和软骨再生的组织工程平台 概述健康透明软骨的组成和结构。然而，评估疗效的能力 在保留和/或再生软骨的PTOA治疗中，存在缺乏标准化诊断的问题 能客观评价PTOA治疗效果的生物标志物。对于临床诊断，关节镜检查- 基于宏观软骨分级系统(Oterbridge，ICRS)和MRI的软骨成分描述 充其量只与软骨成分和材料的定量评估有适度的相关性 与再生组织的机械完整性和功能性能相关的特性。拉曼 光谱学是一种非弹性光散射技术，它反映单个分子的振动键， 对应于关键软骨成分的特定生化构建块：GAG、胶原蛋白和水。 我们建议开发一个全面的拉曼平台来监测软骨成分生物标志物 用于软骨治疗研究的模型系统的层级，包括：1)临床拉曼- 基于关节镜探头，在活体动物研究和患者临床中实现软骨的实时分析 试验，以及2)组织培养兼容的拉曼光谱接口平板读取器，用于快速、非 活体软骨移植的破坏性重复测量分析。我们假设拉曼衍生体 生物标志物可以预测软骨的成分、形态和材料特性 比MRI和关节镜下更准确的软骨保护和/或软骨再生治疗 宏观软骨分级系统(Oterbridge，ICRS)。我们检验了这一假设的层级结构 PTOA治疗.包括体外系统在内的发展模型系统.经 软骨损伤与软骨保护药物治疗、生理学意义上的工程化软骨移植 生理性负载炎性细胞因子，以及来自尸检和关节成形术的人软骨移植 供体和体内系统--一个遭受PTOA损伤、手术修复和药物治疗的绵羊窒息关节 治疗。通过对新出现的软骨疗法的疗效进行客观评估 研发模型系统-体外、体内、临床-拉曼光谱评估可以推动下一步 PTOA干预措施的生成进入临床。将基于拉曼的关节镜技术转化为安全的， 有效的医疗平台可以为临床实践带来变革，使快速高效地识别 常规关节镜下PTOA软骨损伤及新生骨再生监测。

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.