Kostadinova Aneliya, Seifert Barbara, Albrecht Wolfgang, Malsch Guenter, Groth Thomas, Lendlein Andreas, Altankov George
Institute of Biophysics, Bulgarian Academy of Science, Akad. G. Bonchev Str. Bl. 21, 1113 Sofia, Bulgaria.
J Biomater Sci Polym Ed. 2009;20(5-6):821-39. doi: 10.1163/156856209X427005.
It was found previously that membranes based on co-polymers of acrylonitrile (AN) and 2-acrylamido-2-methyl-propansulfonic acid (AMPS) greatly stimulated the functionality and survival of primary hepatocytes. In those studies, however, the pure AN-AMPS co-polymer had poor membrane-forming properties, resulting in quite dense rubber-like membranes. Hence, membranes with required permeability and optimal biocompatibility were obtained by blending the AN-AMPS co-polymer with poly(acrylonitrile) homopolymer (PAN). The amount of PAN (P) and AN-AMPS (A) in the blend was varied from pure PAN (P/A-100/0) over P/A-75/25 and P/A-50/50 to pure AN-AMPS co-polymer (P/A-0/100). A gradual decrease of molecular cut-off of membranes with increase of AMPS concentration was found, which allows tailoring membrane permeability as necessary. C3A hepatoblastoma cells were applied as a widely accepted cellular model for assessment of hepatocyte behaviour by attachment, viability, growth and metabolic activity. It was found that the blend P/A-50/50, which possessed an optimal permeability for biohybrid liver systems, supported also the attachment, growth and function of C3A cells in terms of fibronectin synthesis and P-450 isoenzyme activity. Hence, blend membranes based on a one to one mixture of PAN and AN-AMPS combine sufficient permeability with the desired cellular compatibility for application in bioreactors for liver replacement.
先前发现，基于丙烯腈（AN）和2-丙烯酰胺基-2-甲基丙烷磺酸（AMPS）共聚物的膜极大地刺激了原代肝细胞的功能和存活。然而，在那些研究中，纯AN-AMPS共聚物的成膜性能较差，导致形成相当致密的橡胶状膜。因此，通过将AN-AMPS共聚物与聚丙烯腈均聚物（PAN）共混，获得了具有所需渗透性和最佳生物相容性的膜。共混物中PAN（P）和AN-AMPS（A）的量从纯PAN（P/A-100/0）到P/A-75/25、P/A-50/50，再到纯AN-AMPS共聚物（P/A-0/100）变化。发现随着AMPS浓度的增加，膜的分子截留值逐渐降低，这使得可以根据需要调整膜的渗透性。C3A肝母细胞瘤细胞被用作一种广泛接受的细胞模型，通过附着、活力、生长和代谢活性来评估肝细胞行为。发现对于生物杂交肝系统具有最佳渗透性的P/A-50/50共混物，在纤连蛋白合成和P-450同工酶活性方面也支持C3A细胞的附着、生长和功能。因此，基于PAN和AN-AMPS 1:1混合物的共混膜结合了足够的渗透性和所需的细胞相容性，可用于肝脏替代生物反应器。
