Enhancement of Nutrient Transport and Energy Production of the Intervertebral Disc by the Implantation of Polyurethane Mass Transfer Device

摘要

Low back pain is a common problem that most people experience at some point in their life. Intervertebral disc (IVD) degeneration has been considered closely associated with low back pain. Since the IVD is the largest avascular tissue in the human body, insufficient nutrient supply has been suggested to be one of the etiologies for IVD degeneration. Therefore, enhancing the nutrient transport into the IVD could be a potential treatment strategy for disc degeneration. Mass transfer devices have been used for the purpose of drug delivery and hemodialysis, and similar concept could be applied to the IVD. A porous material with high transport properties implanted in the annulus fibrosus (AF) could be designed to facilitate transport of nutrients from the edge of AF into the nucleus pulposus (NP) region. For most cellular activities in the IVD (e.g., cell proliferation and extracellular matrix production), the adenosine-5'-triphosphate (ATP) is utilized as main energy currency. ATP also serves as an important role in the formation of proteoglycan (PG) and an extracellular signaling molecule. Therefore, the overall objective of this study was to investigate the relationship between porosity and mass transport and mechanical properties of porous polyurethane (PU) scaffolds, as well as the enhancement of nutrient transport and ATP production in the IVD by the implantation of porous PU scaffolds in the AF as mass transfer devices.;The mechanical and mass transport properties of porous PU scaffolds fabricated by the combination of phase inversion and salt leaching method were systematically characterized, and its relationships with porosity were investigated. The results demonstrated that porosity could be utilized to govern both mass transport and mechanical properties of porous scaffolds. The relationships could facilitate the porous PU scaffolds fabrication with specific mass transport and mechanical properties. The effect of implantation of PU mass transfer devices in the IVD was studied. The results demonstrated that compressive stiffness and the height of the IVD could be preserved with the implantation of the devices. The level of ATP, lactate and PG was also found to be increased in the device group. The results indicated that implantation of the PU mass transfer devices could promote nutrient transport and enhance energy production without compromising the mechanical and cellular functions in the IVD. In the last section, the theoretical model of mechano-electrochemical mixture theory was validated using the organ culture of porcine IVD, and different designs of mass transfer device were also theoretically analyzed. The results demonstrated good agreement between experimental and theoretical glucose distribution. In addition, the larger size of the mass transfer device and device with impermeable AF portion could also enhance the glucose concentration and consumption rate at the NP region. The findings of this dissertation contribute to further understanding the effect of implantation of PU mass transfer device in the IVD, and the results could help the development of novel treatment strategies for IVD degeneration and low back pain.