Li R H, Altreuter D H, Gentile F T
CytoTherapeutics, Inc., 2 Richmond Square, Providence, Rhode Island 02906.
Biotechnol Bioeng. 1996 May 20;50(4):365-73. doi: 10.1002/(SICI)1097-0290(19960520)50:4<365::AID-BIT3>3.0.CO;2-J.
Current membrane-based bioartificial organs consist of three basic components: (1) a synthetic membrane, (2) cells that secrete the product of interest, and (3) an encapsulated matrix material. Alginate and agarose have been widely used to encapsulate cells for artificial organ applications. It is important to understand the degree of transport resistance imparted by these matrices in cell encapsulation to determine if adequate nutrient and product fluxes can be obtained. For artificial organs in xenogeneic applications, it may also be important to determine the extent of immunoprotection offered by the matrix material. In this study, diffusion coefficients were measured for relevant solutes [ranging in size from oxygen to immunoglobulin G (IgG)] into and out of agarose and alginate gels. Alginate gels were produced by an extrusion/ionic crosslinking process using calcium while agarose gels were thermally gelled. The effect of varying crosslinking condition, polymer concentration, and direction of diffusion on transport was investigated. In general, 2-4% agarose gels offered little transport resistance for solutes up to 150 kD, while 1.5-3% alginate gels offered significant transport resistance for solutes in the molecular weight range 44-155 kD-lowering their diffusion rates from 10- to 100-fold as compared to their diffusion in water. Doubling the alginate concentration had a more significant effect on hindering diffusion of larger molecular weight species than did doubling the agarose concentration. Average pore diameters of approximately 170 and 147 A for 1.5 and 3% alginate gels, respectively, and 480 and 360 A for 2 and 4% agarose gels, respectively, were estimated using a semiempirical correlation based on diffusional transport of different-size solutes. The method developed for measuring diffusion in these gels is highly reproducible and useful for gels crosslinked in the cylindrical geometry, relevant for studying transport through matrices used in cell immobilization in the hollow fiber configuration. (c) 1996 John Wiley & Sons, Inc.
（1）合成膜，（2）分泌目标产物的细胞，以及（3）包封的基质材料。海藻酸盐和琼脂糖已被广泛用于人工器官应用中细胞的包封。了解这些基质在细胞包封中所带来的传输阻力程度对于确定能否获得足够的营养物质和产物通量非常重要。对于异种应用中的人工器官，确定基质材料提供的免疫保护程度可能也很重要。在本研究中，测量了相关溶质（大小从氧气到免疫球蛋白G（IgG））进出琼脂糖和海藻酸盐凝胶的扩散系数。海藻酸盐凝胶通过使用钙的挤出/离子交联过程制备，而琼脂糖凝胶则通过热凝胶化制备。研究了交联条件、聚合物浓度和扩散方向变化对传输的影响。一般来说，2 - 4%的琼脂糖凝胶对分子量高达150 kD的溶质几乎没有传输阻力，而1.5 - 3%的海藻酸盐凝胶对分子量在44 - 155 kD范围内的溶质具有显著的传输阻力——与它们在水中的扩散相比，其扩散速率降低了10到100倍。将海藻酸盐浓度加倍对阻碍较大分子量物质扩散的影响比将琼脂糖浓度加倍更为显著。分别基于不同大小溶质的扩散传输，使用半经验相关性估计1.5%和3%海藻酸盐凝胶的平均孔径约为170 Å和147 Å，2%和4%琼脂糖凝胶的平均孔径分别为480 Å和360 Å。所开发的用于测量这些凝胶中扩散的方法具有高度可重复性，并且对于在圆柱形几何形状中交联的凝胶很有用，这与研究通过中空纤维配置中用于细胞固定化的基质的传输相关。（c）1996约翰威立父子公司
