| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
,
,
,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:
|
|
 |
|
  Y. Du, E. Lo, S. Ali, and A. Khademhosseini Directed assembly of cell-laden microgels for fabrication of 3D tissue constructs PNAS, July 15, 2008; 105(28): 9522 - 9527. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Lockery, K. J. Lawton, J. C. Doll, S. Faumont, S. M. Coulthard, T. R. Thiele, N. Chronis, K. E. McCormick, M. B. Goodman, and B. L. Pruitt Artificial Dirt: Microfluidic Substrates for Nematode Neurobiology and Behavior J Neurophysiol, June 1, 2008; 99(6): 3136 - 3143. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
