Transport characterization of membranes for immunoisolation.

This study relates to the diffusive transport characterization of hollow fibre membranes used in implantable bio-hybrid organs and other immunoisolatory devices. Techniques were developed to accurately determine the mass transfer coefficients for diffusing species in the 10(2)-10(5) MW range, validated and then used to study one membrane type known to effectively immunoisolate both allografts and xenografts in vivo. Low-molecular-weight diffusing markers included glucose, vitamin B12 and cytochrome C; higher-molecular-weight molecules were bovine serum albumin, immunoglobulin G, apoferritin and a range of fluorescein-tagged dextrans. Overall and fractional mass transfer coefficients through the hollow fibres were determined using a resistance-in-series model for transport. A flowing dialysis-type apparatus was used for the small-molecular-weight diffusants, whereas a static diffusion chamber was used for large-molecular-weight markers. For diffusion measurements of small-molecular-weight solutes, convective artefacts were minimized and the effect of boundary layers on both sides of the membrane were accounted for in the model. In measuring diffusion coefficients of large-molecular-weight species, boundary layer effects were shown to be negligible. Results showed that for small-molecular-weight species (< 13,000 MW) the diffusion coefficient in the membrane was reduced relative to diffusion in water by two to four times. The diffusion rate of large-molecular-weight species was hindered by several thousand-fold over their rate of diffusion in water.

In vivo biostability of a polymeric hollow fibre membrane for cell encapsulation.

The biostability of poly(acrylonitrile-co-vinyl chloride) (P(AN/VC)) hollow fibre membranes was assessed in the rat peritoneal cavity over a 12 month period. The mechanical and chemical stabilities of the hollow fibre membrane (HFM) were characterized by measuring its tensile strength and molecular weight (by gel permeation chromatography) pre-implantation and post-explantation. The stability of the HFM transport properties was determined by molecular weight cut-off (MWCO) and hydraulic permeability (HP). Explanted HFMs were treated with 4 M NaOH to remove adsorbed protein before measuring mechanical, chemical and transport properties. The HFM was stable in vivo for at least 12 months: (i) weight average molecular weight (Mw) at t = 0 was 143,000 g mol-1 (with a polydispersity index (PDI) of 2.3) and at t = 12 months it was 128,000 g mol-1 (with a PDI of 2.8); and (ii) tensile strength at t = 0, 52 +/- 2 mdyne, did not change significantly over time and was 46 +/- 7 mdyne at t = 15 months (P > 0.05 by a two-tailed Student's t-test); and (iii) no significant differences, with respect to standard deviation, were observed in the transport properties: HP was 7.4 +/- 1.5 ml min-1 m-2 mmHg-1 at t = 0 and 7.5 +/- 1.5 ml min-1 m-2 mmHg-1 at t = 12 months, while MWCO (at 90% rejection) was initially 40,000 +/- 8000 g mol-1 and then 54,000 +/- 10,000 g mol-1 at t = 12 months.