Joe Tien Group at Boston University

The Tien Group

Boston University

Department of Biomedical Engineering

44 Cummington Street

Boston, MA 02215

We are an interdisciplinary group of researchers who invent new types of biomaterials, for uses that range from basic studies of quantitative physiology to clinical applications in regenerative medicine. Of particular interest are microfluidic materials whose internal geometries mimic the organization of native vascular networks. With these materials, we seek to solve one of the long-standing challenges in tissue engineering: how to form clinically relevant volumes of tissue that are nourished and drained by functional microvessels. We are currently in our twelfth year at Boston University.

Questions of current interest include:

· How can one synthesize and vascularize three-dimensional (3D) microfluidic materials?

· What quantitative principles govern functional vascularization of biomaterials? Can one distill these principles into a computer algorithm for rational scaffold design?

· How does one scale up vascularized materials to clinically relevant sizes? How do such materials behave when grafted in vivo?

To address these questions, we develop unconventional methods to organize vascular and non-vascular cells and extracellular components into perfused, micropatterned tissues. We use traditional techniques of microvascular physiology (along with a healthy mixture of ideas from vascular cell biology, transport phenomena, biomechanics, and numerical modeling) to analyze, predict, and control the behavior of these tissues.

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: We are located on the 7th floor of the Engineering Research Building (44 Cummington St.), in rooms 713, 715, and 717. [Map]

Phone: (617) 358-3055 [Joe’s office—ERB 717]

(617) 358-2831 [Lab and lounge—ERB 715 & 713]

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 [BME page] [CV] [Google Scholar]	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"
Aimal Khankhel	kaimal10 \| bu_edu	Undergraduate researcher
Rebecca Thompson	rthomp \| bu_edu	Undergraduate researcher
Brent Coisman	bcoisman \| bu_edu	Undergraduate researcher
Keith Wong (2007-2012)	kwong18 \| partners_org whk.keith \| gmail_com	Ph.D. thesis: "Normalization of Microvascular Physiology in Engineered Microvessels via Cyclic Adenosine Monophosphate Supplementation and Artificial Lymphatic Drainage" Postdoctoral fellow with Mehmet Toner (Center for Engineering in Medicine, MGH/Harvard)
Kelvin Chan (2011-2012)	lordkelvin \| gmail_com	M.S. thesis: "Genipin Crosslinked Collagen Microfluidic Scaffolds Form Stable Microvessels In Vitro Using Human Endothelial Cells" Medical student, Albert Einstein College of Medicine
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, LeMaitre Vascular
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)	min.tang-schomer \| tufts_edu	Ph.D. thesis: "In Vitro Engineering of a Microvascular Network" Postdoctoral fellow with David Kaplan (Tufts University, Department of Biomedical Engineering)
Ben Cohen (2012)		Undergraduate in biomedical engineering, Boston University
Jason Pui (2011-2012)		Undergraduate in biomedical engineering, Boston University
Alex Leung (2009-2011)		Medical student, Boston University
Chitrangada Acharya (2010)		Postdoctoral fellow with Dominik Haudenschild (UC Davis, Department of Orthopaedic Surgery)
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
Cate 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

45. Wong, K.H.K., Truslow, J.G., Khankhel, A.H. & Tien, J. Biophysical mechanisms that govern the vascularization of microfluidic scaffolds. in Vascularization: Regenerative Medicine and Tissue Engineering (ed. Brey, E.M.), in press (CRC Press, Boca Raton, FL).

44. Wong, K.H.K., Truslow, J.G., Khankhel, A.H., Chan, K.L.S. & Tien, J., Artificial lymphatic drainage systems for vascularized microfluidic scaffolds. J. Biomed. Mater. Res. A, in press. [Early View]

43. Tien, J., Truslow, J.G. & Nelson, C.M., Modulation of invasive phenotype by interstitial pressure-driven convection in aggregates of human breast cancer cells. PLoS One 2012, 7, e45191. [Corrected PDF + Supporting Information]

42. Leung, A.D., Wong, K.H.K. & Tien, J., Plasma expanders stabilize human microvessels in microfluidic scaffolds. J. Biomed. Mater. Res. A 2012, 100, 1815–1822. [PDF]

41. Wong, K.H.K., Chan, J.M., Kamm, R.D. & Tien, J., Microfluidic models of vascular functions. Annu. Rev. Biomed. Eng. 2012, 14, 205–230. [PDF]

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.), pp. 205-221 (Elsevier, Oxford, U.K., 2012). [PDF]

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 + Supporting Information] [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

Collaborators:

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

Jerome Mertz, Department of Biomedical Engineering, Boston University

Databases and analytical software:

PubMed

ISI Web of Knowledge (here, for BU users)

Horst Ibelgaufts’ COPE (giant cytokine index)