Novel Intra-Tissue Perfusion System for Culturing Thick Liver Tissue

Abstract

Innovative scaffold fabrication, angiogenesis promotion, and dynamic tissue culture techniques have been utilized to improve delivery of media into the core of large tissue constructs in tissue engineering. We have developed here an intra-tissue perfusion (ITP) system, which incorporates an array of seven micron-sized needles as a delivery conduit, to improve mass transfer into the core of thick liver tissues slices (>>300 microm mass transport limit). The ITP system improves the uniformity and distribution of media throughout the tissue, resulting in improved cell viability over the static-cultured controls. The ITP-cultured thick liver slices also exhibit improved phase I and phase II metabolic functions and albumin and urea synthetic functions after 3-day culture, which is the minimal period required by the U.S. Food and Drug Administration (FDA) for studying drug-drug interaction. This ITP system can also be used for culturing other thick tissue constructs of larger dimensions for various in vitro and in vivo applications, including bridging integration of the in vitro cultured constructs into living host tissues.