UC Davis

Articular cartilage, the near-frictionless tissue allowing smooth movement of joints, has a poor intrinsic healing capacity and can degenerate to osteoarthritis due to disease, trauma, or age. Clinical osteoarthritis is a late-stage condition for which disease-modifying opportunities are limited. Therefore, early detection of osteoarthritis is critical to support a paradigm shift from palliation of late disease towards prevention. Unfortunately, early diagnosis of OA is still a challenging, unmet clinical need that must be addressed. On the other hand, cartilage tissue engineering is an emerging strategy at the threshold of clinical translation, holding immense potential to deliver effective curative therapies for osteoarthritis. However, tissue engineers currently depend predominantly on time-consuming, expensive, and destructive techniques to monitor the maturation of engineered tissue, which can be inappropriate or impractical for large-scale biomanufacturing. Therefore, there is also an immediate need to develop nondestructive tools to monitor tissue-engineered cartilage products for both research and clinical applications.Optical techniques such as fluorescence lifetime imaging (FLIm) and optical coherence tomography (OCT) have great potential to address these unmet needs due to their capacity to probe tissue composition and structure spatially and temporally in a nondestructive and noninvasive manner. In this dissertation, the feasibility of using FLIm and OCT for early detection of osteoarthritis and nondestructive monitoring of engineered cartilage is demonstrated, a novel solid-state multispectral FLIm system with improved performance is developed, addressing the limitations of current FLIm instrumentation for clinical and tissue engineering applications. Chapter two describes the basics principle and instrumentation of FLIm and OCT as well as the rationale for their application to cartilage research. In chapter three, the fluorescence properties of native cartilage are studied and the feasibility of using FLIm for the early detection of osteoarthritis is demonstrated. Chapter four demonstrates the potential of bimodal FLIm-OCT as a nondestructive quality control technique for monitoring the growth of tissue-engineered cartilage in a pre-clinical animal model. Chapter five reports the design, development, and characterization of a novel multispectral FLIm system with four-times faster imaging speed, five-times lower measurement variability, and automated gain control for each spectral channel utilizing state-of-art solid-state detectors, addressing the limitation in imaging speed and signal-to-noise ratio of the current FLIm instrument for clinical and tissue engineering applications.