Joe Tien Group at Boston University

The Tien Group

We are a non-profit research organization that studies the quantitative physiology of engineered tissues. Our efforts are focused on one of the long-standing challenges in tissue engineering: how to form functional microvessels that can nourish clinically relevant volumes of tissue. We are currently in our 11^th year at Boston University.

Questions of particular interest include:

· How can one synthesize and vascularize three-dimensional (3D) microfluidic networks within native extracellular matrix scaffolds?

· Which signals—mechanical, chemical, geometric, and/or genetic—are required to induce and retain microvascular function?

· Are the 3D structures of native microvascular networks optimal for engineered tissues? How can the design of networks be improved?

· How can one seamlessly graft vascularized scaffolds in vivo without loss of their function?

To address these questions, we develop unconventional methods to organize cells and extracellular components in vitro into structures that can mimic the 3D histology of native tissues in vivo. We use traditional techniques of microvascular physiology (along with a healthy mixture of ideas from vascular cell biology, chemical engineering, biomechanics, and numerical modeling) to analyze, predict, and control the behavior of engineered microvascular networks.

Below, we invite you to read about the group and its research interests, publications, and resources. For further information, please contact us directly.

GROUP INFORMATION

Principal Investigator: Joe Tien

Address: Boston University

Department of Biomedical Engineering

44 Cummington Street, Room 715

Boston, MA 02215

[map]

Phone: (617) 358-3055 [Joe’s office]

(617) 358-2831 [Lab and lounge]

Fax: (617) 353-6766

RESEARCH INTERESTS

Quantitative physiology of engineered microvessels

Price, G.M., Wong, K.H.K., Truslow, J.G., Leung, A.D., Acharya, C. & Tien, J. Biomaterials 2010, 31, 6182-6189.

Wong, K.H.K., Truslow, J.G. & Tien, J. Biomaterials 2010, 31, 4706-4714.

Truslow, J.G., Price, G.M. & Tien, J. Biomaterials 2009, 30, 4435-4443.

Price, G.M., Chrobak, K.M. & Tien, J. Microvasc. Res. 2008, 76, 46-51.

Nelson, C.M. & Tien, J. Curr. Opin. Biotechnol. 2006, 17, 518-523.

Chrobak, K.M., Potter, D.R. & Tien, J. Microvasc. Res. 2006, 71, 185-196.

Tien, J., Golden, A.P. & Tang, M.D. in Microvascular Research: Biology and Pathology, pp. 1087-1093 (2006).

Techniques for patterning biological materials

Price, G.M., Chu, K.K., Truslow, J.G., Tang-Schomer, M.D., Golden, A.P., Mertz, J. & Tien, J., J. Am. Chem. Soc. 2008, 130, 6664-6665.

Golden, A.P. & Tien, J. Lab Chip 2007, 7, 720-725.

Nelson, C.M. & Tien, J. Curr. Opin. Biotechnol. 2006, 17, 518-523.

Tang, M.D., Golden, A.P. & Tien, J. Adv. Mater. 2004, 16, 1345-1348.

Tang, M.D., Golden, A.P. & Tien, J. J. Am. Chem. Soc. 2003, 125, 12988-12989.

Tien, J., Nelson, C.M. & Chen, C.S. Proc. Natl. Acad. Sci. USA 2002, 99, 1758-1762.

MEMBERS (Current in bold)

Joe Tien

[biosketch]

[BME page]

[CV]

jtien | bu_edu

Principal investigator

James Truslow

[CV]

jtruslow | bu_edu

Postdoctoral fellow

Ph.D. thesis: "Design and Analysis of Engineered Microvasculature via Computational Methods"

M.S. thesis: "Drainage Systems That Maintain Transmural Pressure in Engineered Microvascular Tissue"

Keith Wong

[CV]

keithwhk | bu_edu

Ph.D. student

Kelvin Chan

[resume]

klchan | bu_edu

Master's student

Alex Leung

[resume]

adl29 | bu_edu

M.D. student

Jason Pui

jasonpui | bu_edu

Undergraduate researcher

Aimal Khankhel

kaimal10 | bu_edu

Undergraduate researcher

Gavrielle Price

(2004-2009)

gaviprice | gmail_com

Ph.D. thesis: "Mechanical and Chemical Control of Barrier in Engineered Microvessels"

Postdoctoral fellow with Martin Yarmush (Center for Engineering in Medicine, MGH/Harvard)

Andrew Golden

(2002-2008)

agolden | daktaridx_com

Ph.D. thesis: "Microfluidic Hydrogels for Microvascular Tissue Engineering"

Research scientist, Daktari Diagnostics

Kenneth Chrobak

(2003-2007)

kchrobak | alum_bu_edu

Ph.D. thesis: "Formation of Perfused Microvessels In Vitro, and Their Use as Models of Barrier Function"

Research scientist, Baxter Healthcare

Min Tang

(2002-2005)

mintang | med_upenn_edu

Ph.D. thesis: "In Vitro Engineering of a Microvascular Network"

Postdoctoral fellow with Douglas Smith (University of Pennsylvania, Department of Neurosurgery, Center for Brain Injury and Repair)

Chitrangada Acharya

(2010)

Postdoctoral fellow, UC Davis

Stephanie Steichen

(2008)

Doctoral student in biomedical engineering, UT Austin

Kim Waller

(2007-2008)

Doctoral student in biomedical engineering, Brown University

Russell Condie

(2006)

Doctoral student in biomedical engineering, University of Utah

Hillary Eggert

(2004)

Carthage College, Biology

Caitlyn McCullough

(2003)

M.S., bioengineering, Stanford University (2007)

Wajd Al-Holou

(2002)

M.D., University of Michigan (2009)

Brandon Markway

(2002)

Ph.D., biomedical engineering, Oregon Health and Science University (2010)

PUBLICATIONS

41. Wong, K.H.K., Chan, J.M., Kamm, R.D. & Tien, J., Microfluidic models of vascular functions. Annu. Rev. Biomed. Eng., in press.

40. Tien, J., Wong, K.H.K. & Truslow, J.G. Vascularization of microfluidic hydrogels. in Microfluidic Cell Culture Systems (eds. Bettinger, C.J., Borenstein, J.T. & Tao, S.L.), in press (Elsevier).

39. Truslow, J.G. & Tien, J., Perfusion systems that minimize vascular volume fraction in engineered tissues. Biomicrofluidics 2011, 5, 022201. [PDF]

38. Price, G.M. & Tien, J. Methods for forming human microvascular tubes in vitro and measuring their macromolecular permeability. in Biological Microarrays (Methods in Molecular Biology, vol. 671) (eds. Khademhosseini, A., Suh, K.-Y. & Zourob, M.), pp. 281-293 (Humana Press, Totowa, NJ, 2011). [PDF]

37. Price, G.M., Wong, K.H.K., Truslow, J.G., Leung, A.D., Acharya, C. & Tien, J., Effect of mechanical factors on the function of engineered human blood microvessels in microfluidic collagen gels. Biomaterials 2010, 31, 6182-6189. [PDF]

36. Wong, K.H.K., Truslow, J.G. & Tien, J., The role of cyclic AMP in normalizing the function of engineered human blood microvessels in microfluidic collagen gels. Biomaterials 2010, 31, 4706-4714. [PDF] [Movie]

35. Truslow, J.G., Price, G.M. & Tien, J., Computational design of drainage systems for vascularized scaffolds. Biomaterials 2009, 30, 4435-4443. [PDF]

34. Price, G.M. & Tien, J. Subtractive methods for forming microfluidic gels of extracellular matrix proteins. in Microdevices in Biology and Engineering (eds. Bhatia, S.N. & Nahmias, Y.), pp. 235-248 (Artech House, Boston, MA, 2009). [PDF]

33. Price, G.M., Chu, K.K., Truslow, J.G., Tang-Schomer, M.D., Golden, A.P., Mertz, J. & Tien, J., Bonding of macromolecular hydrogels using perturbants. J. Am. Chem. Soc. 2008, 130, 6664-6665. [PDF] [Methods and Movies]

32. Price, G.M., Chrobak, K.M. & Tien, J., Effect of cyclic AMP on barrier function of human lymphatic microvascular tubes. Microvasc. Res. 2008, 76, 46-51. [PDF]

31. Golden, A.P. & Tien, J., Fabrication of microfluidic hydrogels using molded gelatin as a sacrificial element. Lab Chip 2007, 17, 720-725. [PDF]

30. Nelson, C.M. & Tien, J., Microstructured extracellular matrices in tissue engineering and development. Curr. Opin. Biotechnol. 2006, 17, 518-523. [PDF]

29. Chrobak, K.M., Potter, D.R. & Tien, J., Formation of perfused, functional microvascular tubes in vitro. Microvasc. Res. 2006, 71, 185-196. [PDF] [Movies]

28. Tien, J., Golden, A.P. & Tang, M.D. Engineering of blood vessels. in Microvascular Research: Biology and Pathology, Vol. 2 (eds. Shepro, D. & D'Amore, P.A.), pp. 1087-1093 (Elsevier Academic Press, San Diego, CA, 2006). [PDF]

27. Tang, M.D., Golden, A.P. & Tien, J., Fabrication of collagen gels that contain patterned, micrometer-scale cavities. Adv. Mater. 2004, 16, 1345-1348. [PDF]

26. Gray, D.S., Tien, J. & Chen, C.S., High conductivity elastomeric electronics. Adv. Mater. 2004, 16, 393-397. [PDF]

25. Chen, C.S., Tan, J.L. & Tien, J., Mechanotransduction at cell-matrix and cell-cell contacts. Annu. Rev. Biomed. Eng. 2004, 6, 275-302. [PDF]

24. Tang, M.D., Golden, A.P. & Tien, J., Molding of three-dimensional microstructures of gels. J. Am. Chem. Soc. 2003, 125, 12988-12989. [PDF]

23. Gray, D.S., Tien, J. & Chen, C.S., Repositioning of cells by mechanotaxis on surfaces with micropatterned Young's modulus. J. Biomed. Mater. Res. 2003, 66A, 605-614. [PDF]

22. Tan, J.L., Tien, J., Pirone, D.M., Gray, D.S., Bhadriraju, K. & Chen, C.S., Cells lying on a bed of microneedles: an approach to isolate mechanical force. Proc. Natl. Acad. Sci. USA 2003, 100, 1484-1489. [PDF]

21. Clark, T.D., Ferigno, R., Tien, J., Paul, K.E. & Whitesides, G.M., Template-directed self-assembly of 10-μm-sized hexagonal plates. J. Am. Chem. Soc. 2002, 124, 5419-5426. [PDF]

20. Tien, J., Nelson, C.M. & Chen, C.S., Fabrication of aligned microstructures with a single elastomeric stamp. Proc. Natl. Acad. Sci. USA 2002, 99, 1758-1762. [PDF]

19. Tien, J. & Chen, C.S., Patterning the cellular microenvironment. IEEE Eng. Med. Biol. 2002, 21, 95-98. [PDF]

18. Tan, J.L., Tien, J. & Chen, C.S., Microcontact printing of proteins on mixed self-assembled monolayers. Langmuir 2002, 18, 519-523. [PDF]

17. Tien, J. & Chen, C.S. Microarrays of cells. in Methods of Tissue Engineering (eds. Atala, A. & Lanza, R.), pp. 113-120 (Academic Press, San Diego, CA, 2001).

16. Bowden, N., Tien, J., Huck, W.T.S. & Whitesides, G.M. Mesoscale self-assembly: the assembly of micron- and millimeter-sized objects using capillary forces. in Supramolecular Organization and Materials Design (eds. Jones, W. & Rao, C.N.R.), pp. 103-145 (Cambridge University Press, New York, NY, 2001).

15. Clark, T.D., Tien, J., Duffy, D.C., Paul, K.E. & Whitesides, G.M., Self-assembly of 10-μm-sized objects into ordered three-dimensional arrays. J. Am. Chem. Soc. 2001, 123, 7677-7682. [PDF]

14. Gracias, D.H., Tien, J., Breen, T.L., Hsu, C. & Whitesides, G.M., Forming electrical networks in three dimensions by self-assembly. Science 2000, 289, 1170-1172. [PDF]

13. Dike, L.E., Chen, C.S., Mrksich, M., Tien, J., Whitesides, G.M. & Ingber, D.E., Geometric control of switching between growth, apoptosis, and differentiation during angiogenesis using micropatterned substrates. In Vitro Cell. Dev. Biol. Anim. 1999, 35, 441-448. [PDF]

12. Deng, T., Tien, J., Xu, B. & Whitesides, G.M., Using patterns in microfiche as photomasks in 10-μm-scale microfabrication. Langmuir 1999, 15, 6575-6581. [PDF]

11. Breen, T.L., Tien, J., Oliver, S.R.J., Hadzic, T. & Whitesides, G.M., Design and self-assembly of open, regular, 3D mesostructures. Science 1999, 284, 948-951. [PDF]

10. Lahiri, J., Isaacs, L., Tien, J. & Whitesides, G.M., A strategy for the generation of surfaces presenting ligands for studies of binding based on an active ester as a common reactive intermediate. Anal. Chem. 1999, 71, 777-790. [PDF]

9. Tien, J., Breen, T.L. & Whitesides, G.M., Crystallization of millimeter-scale objects with use of capillary forces. J. Am. Chem. Soc. 1998, 120, 12670-12671. [PDF]

8. Huck, W.T.S., Tien, J. & Whitesides, G.M., Three-dimensional mesoscale self-assembly. J. Am. Chem. Soc. 1998, 120, 8267-8268. [PDF]

7. Marzolin, C., Terfort, A., Tien, J. & Whitesides, G.M., Patterning of a polysiloxane precursor to silicate glasses by microcontact printing. Thin Solid Films 1998, 315, 9-12. [PDF]

6. Tien, J., Xia, Y. & Whitesides, G.M. Microcontact printing of SAMs. in Self-Assembled Monolayers of Thiols (Thin Films, vol. 24) (ed. Ulman, A.), pp. 227-250 (Academic Press, San Diego, CA, 1998).

5. Xia, Y., Venkateswaran, N., Qin, D., Tien, J. & Whitesides, G.M., Use of electroless silver as the substrate in microcontact printing of alkanethiols and its application in microfabrication. Langmuir 1998, 14, 363-371. [PDF]

4. Mrksich, M., Dike, L.E., Tien, J., Ingber, D.E. & Whitesides, G.M., Using microcontact printing to pattern the attachment of mammalian cells to self-assembled monolayers of alkanethiolates on transparent films of gold and silver. Exp. Cell Res. 1997, 235, 305-313. [PDF]

3. Tien, J., Terfort, A. & Whitesides, G.M., Microfabrication through electrostatic self-assembly. Langmuir 1997, 13, 5349-5355. [PDF]

2. Xia, Y., Tien, J., Qin, D. & Whitesides, G.M., Non-photolithographic methods for fabrication of elastomeric stamps for use in microcontact printing. Langmuir 1996, 12, 4033-4038. [PDF]

1. Shaw, G.L. & Tien, J., Energy levels of quark atoms. Phys. Rev. D 1993, 47, 5075-5078. [PDF]

FUNDING

Effect of Interstitial Pressure on Epithelial Invasion from Human Mammary Ducts (DoD/Army W81XWH-09-1-0565)

Engineering Functional Lymphatic Networks In Vitro (NIH/NHLBI R21 HL092335)

Synthesis and Characterization of Patterned Microvascular Networks (NIH/NIBIB R01 EB005792)

Self-Assembly of Mesostructured Biomaterials (NIH/NIBIB R21 EB003157)

In Vitro Synthesis of a Microvascular Network (NIH/NIBIB R21 EB002228)

Use of Microfabrication and Self-Assembly in Tissue Engineering (Whitaker Foundation RG-02-0344)

Dynamic Substrates for Cell Culture (BU Special Program for Research Initiation Grants)

Self-Assembly of Gels (BU Provost’s Innovation Fund)

Response of Endothelial Cells to Cell-Cell Contact (NIH/NHLBI F32 HL010486)

LINKS

How to join our research program:

· Postdoctoral fellows:

Interested postdoctoral candidates should send us a detailed cover letter, CV, and a list of three professional references. We look for candidates with a robust track record of publication and innovation.

· Graduate students:

Graduate students must apply through one of the doctoral programs listed below—we are especially interested in applicants with a strong quantitative background and excellent technical skills:

Department of Biomedical Engineering

NIH Training Program in Quantitative Biology and Physiology (for BME program)

Program in Molecular Biology, Cell Biology, and Biochemistry

Division of Materials Science and Engineering

Late Entry Accelerated Program (LEAP) in Biomedical Engineering

MD/PhD program at Boston University School of Medicine

· Undergraduate students:

Undergraduate students should send us a brief explanatory letter, transcript, and description of any prior research experience. We seek students who learn quickly, work hard, and have impeccable ethics.

Resources at BU:

Core facilities (lithography, imaging, and materials characterization) in the Department of Biomedical Engineering

Core facilities (flow cytometry, microarrays, transgenics, etc.) at the Medical Center

Core facilities (lithography, SEM) in the Photonics Center

Library catalog

Science and Engineering Library

Alumni Medical Library

Collaborators:

Celeste M. Nelson, Department of Chemical Engineering, Princeton University

Jerome Mertz, Department of Biomedical Engineering, Boston University

Databases and analytical software:

PubMed