UC Riverside

In the first part of this dissertation, the development of an osmotic transport device (OTD) for the treatment of severe spinal cord injury is presented. Herein, an osmotic transport device was designed for the reduction of edema in spinal cord injury, in which many different limitations and issues needed to be addressed including chemical, physiological, and manufacturing. This design was analyzed by a finite element method to determine device parameter effects on extraction rate, and shown, with later in-vivo parameters, to have an extraction rate exceeding the volume required to reduce tissue water levels to uninjured levels. While this rate was almost an order of magnitude greater than the volume needed to be removed, calculations of physiological restrictions on device effectiveness showed there is a lowest tissue water content that the device could achieve was above uninjured levels.

Fabrication of the device was made with materials that would be biocompatible for the time course of edema. Following fabrication, the extraction rate of the device was analyzed via a densimitry method. Evaluation, with later in-vivo parameters, showed good agreement with the extraction rate obtained from finite element analysis. Finally, testing was done in-vivo to determine the device’s effect on the water content of an injured spinal cord and shown to significantly reduce water content in injured tissue.

The second part of this dissertation focuses on furthering the understanding of crowded protein osmotic pressure. Herein, a concentrating osmometer was developed and shown to provide concentrated osmotic pressure results similar to literature values in less time and requiring less protein. Additionally, the free-solvent based model was developed for ion hydration and for the determination of association values in protein-protein complexes.

Analysis was done of concentrated osmotic pressure for various sodium salts and showed large variations in osmotic pressure. Also, that smaller ion with large charge densities, like F-, and Cl-, bound to proteins in greater numbers and developed systems with higher protein hydrations. Conversely, larger ions with weaker charge densities, like I- and SCN-, had lower ion binding and systems with lower protein hydrations.