Elucidating the structural and functional properties of poly(acrylonitrile-vinylchloride) phase-inversion membranes and their influence in cell encapsulation.

摘要

Poly(acrylonitrile-vinylchloride) (PAN-PVC) cell encapsulation membranes have been repeatedly found to allow sufficient exchange of soluble factors to maintain extended cell viability in a variety of tissues. However, characterization of the hollow fiber membranes' (HFM) transport has been limited to properties important to filtration and rarely extended to the membrane's diffusivity. In addition, PAN-PVC HFM have historically been viewed as having similar characteristics though a wide variety of formulations have been employed. To progress, a better understanding of the relationship between membrane diffusive permeability and the biology of the encapsulated cells is required. The central hypothesis of this Ph.D. thesis was that the magnitude of the sustained release of cell-derived soluble factors from a HFM-based cell encapsulation device is a function of the diffusive permeability of the encapsulation membrane. Two major aspects of PAN-PVC HFM were explored: an examination of the structural and transport properties of PAN-PVC HFM and the role transport plays in various encapsulated cell properties. The first study examined how different precipitation conditions affected the phase-inversion membrane's dense selective surface. It was found that the surface consisted of nodular elements whose size depended on the precipitation conditions used and could be related to the measured transport properties. The second study examined the role of various polymer solution formulations used in PAN-PVC HFM fabrication found in the cell encapsulation literature. The HFM were examined and found to exhibit a wide range of cross-sectional and dense selective surface architectures. In addition, the membranes demonstrated a range of transport properties extending over several orders of magnitude. PC12 cells were encapsulated in the HFM to examine cell mass viability. Independent of membrane permeability, the cell mass viability ranged between 82 and 90%. The third study extended this investigation to examine other biological parameters of the encapsulated cells. The encapsulated cell mass size, proliferative capacity, and secreted cell product release all correlated strongly to diffusive characterization (convective sieving characterization was weakly correlated). In the future, the findings of these studies will lead to improved cell encapsulation devices due to better defined starting specifications and will encourage better characterization of cell encapsulation devices.