Simulation of oxygen carrier mediated oxygen transport to C3A hepatoma cells housed within a hollow fiber bioreactor

Sullivan, Jesse P.; Gordon, Jason; Palmer, Andre F.

doi:10.1002/bit.20673

Cited by 31 publications

(37 citation statements)

References 65 publications

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“…Also, mPEG-bRBCs could be cross-linked with gluteraldehyde to further alter the P 50 for oxygenation in bio-artificial devices (Gordon et al, 2005;Sullivan et al, 2006). Before application of this novel blood substitute, the most important concern will be the safety of the bovine blood supply.…”

Section: Discussionmentioning

confidence: 99%

Conjugation of methoxypolyethylene glycol to the surface of bovine red blood cells

Gundersen

Palmer

2006

Biotech & Bioengineering

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Methoxypolyethylene glycol (mPEG) covalently bound to the surface of human red blood cells (hRBCs) has been shown to decrease immunological recognition of hRBC surface antigens (Bradley et al., 2002). However, there is an increasing shortage of hRBC donations, thus making hRBCs scarce and expensive (Davey, 2004; Riess, 2001). The goal of this study is to similarly PEGylate the surface of bovine RBCs (bRBCs) with the aim of reducing the demand on human blood donations needed for blood transfusions. This study investigates the feasibility of modifying the surface of bRBCs with the succinimidyl ester of methoxypolyethylene glycol propionic acid (SPA-mPEG) for use as a potential blood substitute. The oxygen binding affinity of PEGylated bRBCs was moderately increased with increasing initial SPA-mPEG concentrations up to 4 mM when reacted with bRBCs at a hematocrit of 12%. Oxygen transport simulations verified that SPA-mPEG conjugated bRBCs could still transport oxygen to pancreatic islet tissues even under extreme conditions. PEGylated bRBCs reconstituted to a hematocrit of 40% exhibited viscosities on the order of approximately 3 cp, similar to hRBCs at the same hematocrit. Taken together, the results of this study demonstrate the success of PEGylating bRBCs to yield modified cells with oxygen binding, transport and flow properties similar to that of hRBCs.

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Section: Discussionmentioning

confidence: 99%

Conjugation of methoxypolyethylene glycol to the surface of bovine red blood cells

Gundersen

Palmer

2006

Biotech & Bioengineering

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“…This has been demonstrated by extensive simulation work conducted in our lab. [19][20][21][22] Recent experimental studies also showed that supplementation of bovine red blood cells (bRBCs) into the circulating cell culture medium improved O 2 transport to cultured C3A cells in a HF bioreactor. 23,24 In the presence of bRBCs, the molar ratio of lactate production to glucose consumption of hepatoma cells was remarkably reduced, while albumin synthesis increased substantially, which indicates highly efficient cellular metabolism and synthetic function.…”

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confidence: 99%

Hemoglobin Regulates the Metabolic, Synthetic, Detoxification, and Biotransformation Functions of Hepatoma Cells Cultured in a Hollow Fiber Bioreactor

Chen

Palmer

2010

Tissue Engineering Part A

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Hepatic hollow fiber (HF) bioreactors constitute one type of extracorporeal bioartificial liver assist device (BLAD). Ideally, cultured hepatocytes in a BLAD should closely mimic the in vivo oxygenation environment of the liver sinusoid to yield a device with optimal performance. However, most BLADs, including hepatic HF bioreactors, suffer from O 2 limited transport toward cultured hepatocytes, which reduces their performance. We hypothesize that supplementation of hemoglobin-based O 2 carriers into the circulating cell culture medium of hepatic HF bioreactors is a feasible and effective strategy to improve bioreactor oxygenation and performance. We examined the effect of bovine hemoglobin (BvHb) supplementation (15 g/L) in the circulating cell culture medium of hepatic HF bioreactors on hepatocyte proliferation, metabolism, and varied liver functions, including biosynthesis, detoxification, and biotransformation. It was observed that BvHb supplementation supported the maintenance of a higher cell mass in the extracapillary space, improved hepatocyte metabolic efficiency (i.e., hepatocytes consumed much less glucose), improved hepatocyte capacity for drug metabolism, and conserved both albumin synthesis and ammonia detoxification functions compared to controls (no BvHb supplementation) under the same experimental conditions.

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“…108 Besides implementing MM oxygen consumption of hepatocytes, hemoglobin model as an oxygen carrier is also included.…”

Section: Computer Fluid Dynamic "Cfd… Modeling Of Ebalmentioning

confidence: 99%

Current development of bioreactors for extracorporeal bioartificial liver (Review)

et al. 2010

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The research and development of extracorporeal bioartificial liver is gaining pace in recent years with the introduction of a myriad of optimally designed bioreactors with the ability to maintain long-term viability and liver-specific functions of hepatocytes. The design considerations for bioartificial liver are not trivial; it needs to consider factors such as the types of cell to be cultured in the bioreactor, the bioreactor configuration, the magnitude of fluid-induced shear stress, nutrients' supply, and wastes' removal, and other relevant issues before the bioreactor is ready for testing. This review discusses the exciting development of bioartificial liver devices, particularly the various types of cell used in current reactor designs, the state-of-the-art culturing and cryopreservation techniques, and the comparison among many today's bioreactor configurations. This review will also discuss in depth the importance of maintaining optimal mass transfer of nutrients and oxygen partial pressure in the bioreactor system. Finally, this review will discuss the commercially available bioreactors that are currently undergoing preclinical and clinical trials.

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Simulation of oxygen carrier mediated oxygen transport to C3A hepatoma cells housed within a hollow fiber bioreactor

Cited by 31 publications

References 65 publications

Conjugation of methoxypolyethylene glycol to the surface of bovine red blood cells

Conjugation of methoxypolyethylene glycol to the surface of bovine red blood cells

Hemoglobin Regulates the Metabolic, Synthetic, Detoxification, and Biotransformation Functions of Hepatoma Cells Cultured in a Hollow Fiber Bioreactor

Current development of bioreactors for extracorporeal bioartificial liver (Review)

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