HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: fj.06-7117comv1 21/3/790    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tsang, V. L. Articles by Bhatia, S. N. Search for Related Content PubMed PubMed Citation Articles by Tsang, V. L. Articles by Bhatia, S. N.

Fabrication of 3D hepatic tissues by additive photopatterning of cellular hydrogels

Valerie Liu Tsang^*, Alice A. Chen, Lisa M. Cho^*, Kyle D. Jadin^*, Robert L. Sah^*, Solitaire DeLong^||, Jennifer L. West^|| and Sangeeta N. Bhatia^*,,,,1

^* Department of Bioengineering, University of California, San Diego, La Jolla, California, USA;

Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, and

Department of Electrical Engineering and Computer Science,

Division of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA; Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; and

^|| Department of Bioengineering, Rice University, Houston, Texas, USA

¹Correspondence: Massachusetts Institute of Technology, 77 Massachusetts Ave., E19–502D, Cambridge, MA 02139, USA. E-mail: sbhatia{at}mit.edu

We have fabricated a hepatic tissue construct using a multilayer photopatterning platform for embedding cells in hydrogels of complex architecture. We first explored the potential of established hepatocyte culture models to stabilize isolated hepatocytes for photoencapsulation (e.g., double gel, Matrigel, cocultivation with nonparenchymal cells). Using photopolymerizable PEG hydrogels, we then tailored both the chemistry and architecture of the hydrogels to further support hepatocyte survival and liver-specific function. Specifically, we incorporated adhesive peptides to ligate key integrins on these adhesion-dependent cells. To identify the appropriate peptides for incorporation, the integrin expression of cultured hepatocytes was monitored by flow cytometry and their functional role in cell adhesion was assessed on full-length extracellular matrix (ECM) molecules and their adhesive peptide domains. In addition, we modified the hydrogel architecture to minimize barriers to nutrient transport for these highly metabolic cells. Viability of encapsulated cells was improved in photopatterned hydrogels with structural features of 500 µm in width over unpatterned, bulk hydrogels. Based on these findings, we fabricated a multilayer photopatterned PEG hydrogel structure containing the adhesive RGD peptide sequence to ligate the ₅ß₁ integrin of cocultured hepatocytes. Three-dimensional photopatterned constructs were visualized by digital volumetric imaging and cultured in a continuous flow bioreactor for 12 d where they performed favorably in comparison to unpatterned, unperfused constructs. These studies will have impact in the field of liver biology as well as provide enabling tools for tissue engineering of other organs.—Liu Tsang, V., Chen, A. A., Cho, L. M., Jadin, K. D., Sah, R. L., DeLong, S., West, J. L., Bhatia, S. N. Fabrication of 3D hepatic tissues by additive photopatterning of cellular hydrogels.

Key Words: tissue engineering • liver • hepatic • PEG • microscale

This article has been cited by other articles:

				M. Dvir-Ginzberg, T. Elkayam, and S. Cohen Induced differentiation and maturation of newborn liver cells into functional hepatic tissue in macroporous alginate scaffolds FASEB J, May 1, 2008; 22(5): 1440 - 1449. [Abstract] [Full Text] [PDF]