Abstract
Two different cryogels composed of copolymer of acrylonitrile (AN) and N-vinyl-2-pyrrolidone (NVP) (poly(AN-co-NVP)) and interpenetrated polymer networks (IPN) of chitosan and poly(N-isopropylacrylamide) (poly(NiPAAm)-chitosan) were fabricated by gelation at sub-zero temperatures. The two cryogels possess an interconnected network of macropores of size 20–100μm and efficient transport properties as determined by physiochemical analysis. Both cryogels support in vitro growth and function of fibroblasts (COS-7) and human liver hepatocarcinoma cells (HepG2). The cryogels are hemocompatible as demonstrated by low albumin adsorption and platelet adherence. Furthermore, in vivo implantation of poly(NiPAAm)-chitosan cryogel in mice shows its biocompatibility with the surrounding tissue. Primary rat hepatocytes grown on poly(NiPAAm)-chitosan cryogel for 96h formed cellular aggregates and maintained their functions in terms of, ammonia removal, ureagenesis and drug detoxification. Cryogel-based closed continuous bioreactor systems could maintain HepG2 cells at high density for 7 days. Off-line clinical evaluation of these cryogel-based bioreactors showed the ability of immobilized cells to detoxify circulating plasma obtained from patients with acute on chronic liver failure (ACLF). Altogether, the presented data suggests cryogels as a potential bioreactor matrix for bio-artificial liver support system.
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