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Tissue Engineering I pp 1–46Cite as

Tissue Assembly Guided via Substrate Biophysics: Applications to Hepatocellular Engineering

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Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 102))

Abstract

The biophysical nature of the cellular microenvironment, in combination with its biochemical properties, can critically modulate the outcome of three-dimensional (3-D) multicellular morphogenesis. This phenomenon is particularly relevant for the design of materials suitable for supporting hepatocellular cultures, where cellular morphology is known to be intimately linked to the functional output of the cells. This review summarizes recent work describing biophysical regulation of hepatocellular morphogenesis and function and focuses on the manner by which biochemical cues can concomitantly augment this responsiveness. In particular, two distinct design parameters of the substrate biophysics are examined – microtopography and mechanical compliance. Substrate microtopography, introduced in the form of increasing pore size on collagen sponges and poly(glycolic acid) (PGLA) foams, was demonstrated to restrict the evolution of cellular morphogenesis to two dimensions (subcellular and cellular void sizes) or induce 3-D cellular assembly (supercellular void size). These patterns of morphogenesis were additionally governed by the biochemical nature of the substrate and were highly correlated to resultant levels of cell function. Substrate mechanical compliance, introduced via increased chemical crosslinking of the basement membrane, Matrigel, and polyacrylamide gel substrates, also was shown to be able to induce active two-dimensional (2-D, rigid substrates) or 3-D (malleable substrates) cellular reorganization. The extent of morphogenesis and the ensuing levels of cell function were highly dependent on the biochemical nature of the cellular microenvironment, including the presence of increasing extracellular matrix (ECM) ligand and growth-factor concentrations. Collectively, these studies highlight not only the ability of substrate biophysics to control hepatocellular morphogenesis but also the ability of biochemical cues to further enhance these effects. In particular, results of these studies reveal novel means by which hepatocellular morphogenesis and assembly can be rationally manipulated leading to the strategic control of the expression of liver-specific functions for hepatic tissue-engineering applications.

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Abbreviations

GF:

Growth Factor

EGF:

Epidermal Growth Factor

HGF:

Hepatocyte Growth Factor

FN:

Fibronectin

PBS:

Phosphate-buffered Saline

DMEM:

Dulbecco's Modified Eagle Medium

BISAAm:

methylenebisacrylamide

AAm:

acrylamide

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Acknowledgments

This work was supported in part by: NIH NIBIB P41 grant (EB000922-01), NSF CAREER grant (BES9733007); Merck Exploratory Research Award; Johnson & Johnson Discovery Award; the Rutgers SROA Award; and the NIH-sponsored Rutgers UMDNJ Biotechnology Training Program. Technical help from Perry Lancin, Thomas Brieva, and Anouska Dasgupta, and laboratory access by Professor Frederick Kauffman are gratefully acknowledged.

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  1. Department of Biomedical Engineering, Department of Chemical and Biochemical Engineering, C230 Engineering, 98 Brett Road, 08854, Piscataway, NJ, USA

    Eric J. Semler, Colette S. Ranucci & Prabhas V. Moghe

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  1. Eric J. Semler
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  2. Colette S. Ranucci
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  3. Prabhas V. Moghe
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Correspondence to Prabhas V. Moghe .

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Kyongbum Lee David Kaplan

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Semler, E.J., Ranucci, C.S., Moghe, P.V. (2006). Tissue Assembly Guided via Substrate Biophysics: Applications to Hepatocellular Engineering. In: Lee, K., Kaplan, D. (eds) Tissue Engineering I. Advances in Biochemical Engineering/Biotechnology, vol 102. Springer, Berlin, Heidelberg . https://doi.org/10.1007/10_012

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