UC Davis

Cardiovascular disease is the number one cause of death in the world. Vessel replacement with tissue engineered vascular graft (TEVG) is an available treatment for this type of diseases. Currently TEVGs are still under extensive investigation in terms of scaffold material selection and processing, graft maturating and recellularization strategies, and validation of graft functionality post implantation. The conventional measurements of TEVG properties are destructive, causing the studies of TEVG manufacturing to be expensive and time-consuming. In this dissertation, we built and examined a set of optical imaging tools for non-destructively monitoring TEVG properties to facilitate the development of TEVG.In the first part, we report a multi-spectral fluorescence lifetime imaging (FLIm) device that measures the tissue autofluorescence (e.g., collagen, elastin). We investigated the potential of using this device to non-destructively monitor the biochemical and biomechanical properties of the biomaterials used to develop TEVGs. This study has shown a strong correlation between the fluorescence parameters (lifetime, spectral ratio) and the results of conventional measurement (collagen content, Young’s Modulus, ultimate tensile strength), and has demonstrated the capability of FLIm to help inform about scaffold material selection and processing. In the second part, we report the design and engineering of a bioreactor where the TEVG can be cultured in situ under a controlled environment and pulsatile flow that simulates physiological conditions. In this study, we adopted the FLIm device for in situ imaging of the intraluminal surface of TEVG when cultured inside the bioreactor. In addition, an exogenous continuous wave (cw) fluorescence imaging modality was also incorporated in the FLIm device. To demonstrate its capability of in situ imaging inside the bioreactor, a TEVG was seeded with enhanced green fluorescence protein (eGFP) labeled human mesenchymal stem cells (hMSC) and mounted inside the bioreactor. The TEVG was then scanned with this FLIm and exogenous cw fluorescence imaging system. The presence of cells was captured by the FLIm image with cell seeded regions showing lower lifetime value, validated by the co-registered eGFP fluorescence image acquired simultaneously by our single system. In the third part, we report the design and engineering of an intravascular multi-modal imaging approach combining FLIm and optical coherence tomography (OCT). The addition of OCT modality can provide a high-resolution 3D structural image of the TEVG. We demonstrated the system performance by imaging an antigen removed saphenous vein (SV) and successfully acquired both FLIm and OCT images of the intraluminal surface of SV, allowing a comprehensive assessment of graft biochemical and structural properties. In summary, here we describe and discuss the three optical systems designed for non-destructive monitoring of the TEVG properties. Current findings show the potential of these optical systems as valuable tools to optimize and improve the manufacturing of TEVG.