Enhanced Oxygen Availability Improves Liver‐specific Functions of the AMC Bioartificial Liver
ABSTRACT Long-term culturing of primary porcine hepatocytes (PPH) inside the Academic Medical Center (AMC)-bioartificial liver is characterized by increased anaerobic glycolysis. Recommendations to increase oxygen availability were proposed in a previous numerical study and were experimentally evaluated in this study. Original bioreactors as well as new configuration bioreactors with 2.2-fold thinner nonwoven matrix and 2-fold more capillaries were loaded with PPHs and oxygenated with different gas oxygen pressures resulting in medium pO2 (pO2-med) of either 135-150 mm Hg or 235-250 mm Hg. After 6 days culturing, new configuration bioreactors with pO2-med of 250 mm Hg showed significantly reduced anaerobic glycolysis, 60% higher liver-specific functions, and increased transcript levels of five liver-specific genes compared to the standard bioreactor cultures. Changed bioreactor configuration and increasing pO2-med contributed equally to these improvements. Histological examination demonstrated small differences in cell organization. In conclusion, higher metabolic stability and liver-specific functionality was achieved by enhanced oxygen availability based on a prior modeling concept.
Article: An Emerging Paradigm in Tissue Engineering: From Chemical Engineering to Developmental Engineering for Bioartificial Tissue Formation through a Series of Unit Operations that Simulate the In Vivo Successive Developmental Stages†[show abstract] [hide abstract]
ABSTRACT: The field of Tissue Engineering is in a critical stage, with the need to replace the trial-and-error methods (which, so far, are the most-often used) with rational methodologies. The opinions of several research groups expressed in the literature, as well as recent research efforts, seem to converge on a change of direction toward in vitro recapitulation of the in vivo process of tissue formation (biomimetic processes), replacing the three-dimensional (3D) cell growth and differentiation paradigm that is currently practiced. However, what the fundamental principles for the ex vivo creation of a biological implant are and how these could be translated to process design criteria for biomimetic processes is still unclear. Chemical Engineering has already offered to Tissue Engineering various tools, such as biomaterials and bioreactors, but its contribution to the development of a scientific basis for Tissue Engineering for the design of biomimetic process now has become critical. The intellectual core of chemical engineering in process design, based on the synthesis of processes from the assembly of unit operations, can provide a methodological framework suitable for the development of a rational biomimetic methodology in Tissue Engineering, with the unit operations recapitulating the successive stages of in vivo tissue development. In this article, we describe (i) why and how biomimetic processes should be designed to synchronize the evolution of variables that describe the biological transformations during the tissue development, (ii) how information from developmental biology can be used for the design of biomimetic processes, and (iii) from where the scientific and technical feasibility of designing such processes arises.01/2011;