Development of BRET detection systems: tools for functional proteomics and drug discovery

关节软骨的内部结构对其生物力学功能至关重要。软骨是体内最复杂和最难检查的组织之一。其功能特征的维持在很大程度上取决于组织的内部微观结构，而传统的关节镜只能给出表面的视图，而不能提供内部结构的信息。活检检查也会破坏组织的完整性，使其无法同时检查组织的结构和功能。因此，结构-功能关系对软骨疾病的研究和临床治疗技术的进步至关重要。骨关节炎的特点是严重破坏软骨基质。自体软骨细胞植入（ACI）治疗作为一种修复软骨缺损的方法的出现，进一步增加了对软骨结构和功能检查的临床技术的兴趣。共聚焦显微镜的发展首次促进了对负载组织的内部检查，使直接检查组织结构和功能之间的关系成为可能。为了便于软骨结构的临床检查，研制了一种原型共聚焦关节镜。这反过来又可以推断出组织的功能特征。软骨几乎没有内在修复，因此不需要活检。因此，特别是对软骨而言，发达的技术有望使检查达到以前不可能达到的详细水平。目前的关节镜原型已经证明了一个真正的临床仪器的可行性。这项拨款申请寻求资金进行初步临床试验，以获得足够的实际反馈，使设计和建造临床就绪的系统成为可能。

The internal structure of articular cartilage is critical to its biomechanical function. Cartilage is one of the most intricate and difficult tissues to examine in-vivo. Maintenance of its functional characteristics depends heavily of the internal microstructure of the tissue, while conventional arthroscopy can only give a view of the surface and provides no information on the internal structure. Biopsy examination can also destroy the integrity of the tissue, making it impossible to concurrently examine the structure and function of the tissue. The structure-function relationship is thus critical to the study and the advancement of clinical treatment techniques for cartilage disorders. Osteoarthritis is characterized by severe disruption to the cartilage matrix. The emergence of autologous chondrocyte implant (ACI) therapy as a method for repairing cartilage defects has further increased interest in clinical techniques for the examination of cartilage structure and function. The development of confocal microscopy facilitates internal examination of loaded tissue for the first time, enabling direct examination of the association between structure and function of the tissue. A prototype confocal arthroscope has been developed to facilitate clinical examination of cartilage structure. This, in turn, allows the functional characteristics of the tissue to be deduced. Cartilage exhibits little intrinsic repair making biopsies undesirable. Thus, with respect to cartilage in particular, the developed technologies promise to enable examination to a level of detail which was previously impossible. The current prototype arthroscope has demonstrated the feasibility of a genuine clinical instrument. This grant application seeks funds to conduct initial clinical trials in order to gain sufficient practical feedback to enable design and construction of a clinically ready system.