Annals of Biomedical Engineering

, Volume 35, Issue 8, pp 1357–1367 | Cite as

In Vitro Characterization of a Compliant Biodegradable Scaffold with a Novel Bioreactor System

  • Antonio R. Webb
  • Bryan D. Macrie
  • Ananda S. Ray
  • Jack E. Russo
  • Andrew M. Siegel
  • Matthew R. Glucksberg
  • Guillermo A. Ameer


The influence of scaffold compliance on blood vessel tissue engineering remains unclear and compliance mismatch issues are important to an in vivo tissue-engineering approach. We have designed and constructed a modular bioreactor system that is capable of imparting pulsatile fluid flow while simultaneously measuring vessel distension with fluid pressure changes in real time. The setup uses a pneumatic PID control system to generate variable fluid pressure profiles via LabVIEW and an LED micrometer to monitor vessel distension to an accuracy of ±2 μm. The bioreactor was used to measure the compliance of elastomeric poly(1,8-octanediol citrate) (POC) scaffolds over physiologically relevant pressure ranges. The compliance of POC scaffolds could be adjusted by changing polymerization conditions resulting in scaffolds with compliance values that ranged from 3.8 ± 0.2 to 15.6 ± 4.6%/mmHg × 10−2, depending on the distension pressures applied. Furthermore, scaffolds that were incubated in phosphate-buffered saline for 4 weeks exhibited a linear increase in compliance (2.6 ± 0.9 to 7.7 ± 1.2%/mmHg × 10−2) and were able to withstand normal physiological blood pressure without bursting. The ability to tailor scaffold compliance and easily measure vessel compliance in real time in vitro will improve our understanding of the role of scaffold compliance on vascular cell processes.


Tissue engineering Blood vessels Bypass grafts Bioreactor Pulsatile pressure Cardiovascular Compliance measurement 


  1. 1.
    Abbott W. M., J. Megerman, J. E. Hasson, G. L’Italien, D. F. Warnock 1987 Effect of compliance mismatch on vascular graft patency. J. Vasc. Surg. 5:376–382PubMedCrossRefGoogle Scholar
  2. 2.
    Ballyk P. D., C. Walsh, J. Butany, M. Ojha 1998 Compliance mismatch may promote graft-artery intimal hyperplasia by altering suture-line stresses. J. Biomech. 31:229–237PubMedCrossRefGoogle Scholar
  3. 3.
    Barron V., E. Lyons, C. Stenson-Cox, P. E. McHugh, A. Pandit 2003 Bioreactors for cardiovascular cell and tissue growth: A review. Ann. Biomed. Eng. 31:1017–1030PubMedCrossRefGoogle Scholar
  4. 4.
    Bilodeau K., F. Couet, F. Boccafoschi, D. Mantovani 2005 Design of a perfusion bioreactor specific to the regeneration of vascular tissues under mechanical stresses. Artif. Organs. 29:906–912PubMedCrossRefGoogle Scholar
  5. 5.
    Carnagey J., D. Hern-Anderson, J. Ranieri, C. E. Schmidt 2003 Rapid endothelialization of photofix natural biomaterial vascular grafts. J. Biomed. Mater. Res. B. 65B:171–179CrossRefGoogle Scholar
  6. 6.
    Chamiot-Clerc P., X. Copie, J. F. Renaud, M. Safar, X. Girerd 1998 Comparative reactivity and mechanical properties of human isolated internal mammary and radial arteries. Cardiovasc. Res. 37:811–819PubMedCrossRefGoogle Scholar
  7. 7.
    Dobrin P. B. 1984 Mechanical behavior of vascular smooth muscle in cylindrical segments of arteries in vitro. Ann. Biomed. Eng. 12:497–510PubMedCrossRefGoogle Scholar
  8. 8.
    Girerd X. J., C. Acar, J. J. Mourad, P. Boutouyrie, M. E. Safar, S. Laurent 1992 Incompressibility of the human arterial wall: An in vitro ultrasound study. J. Hypertens. Suppl. 10:S111–114PubMedGoogle Scholar
  9. 9.
    Greisler H. P., K. A. Joyce, D. U. Kim, S. M. Pham, S. A. Berceli, H. S. Borovetz 1992 Spatial and temporal changes in compliance following implantation of bioresorbable vascular grafts. J. Biomed. Mater. Res. 26:1449–1461PubMedCrossRefGoogle Scholar
  10. 10.
    Hahn M. S., M. K. McHale, E. Wang, R. H. Schmedlen, J. L. West 2007 Physiologic pulsatile flow bioreactor conditioning of poly(ethylene glycol)-based tissue engineered vascular grafts. Ann. Biomed. Eng. 35:190–200PubMedCrossRefGoogle Scholar
  11. 11.
    Kim B. S., J. Nikolovski, J. Bonadio, D. J. Mooney 1999 Cyclic mechanical strain regulates the development of engineered smooth muscle tissue. Nat. Biotechnol. 17:979–983PubMedCrossRefGoogle Scholar
  12. 12.
    L’Heureux N., N. Dusserre, G. Konig, B. Victor, P. Keire, T. N. Wight, N. A. Chronos, A. E. Kyles, C. R. Gregory, G. Hoyt, R. C. Robbins, T. N. McAllister 2006 Human tissue-engineered blood vessels for adult arterial revascularization. Nat. Med. 12:361–365PubMedCrossRefGoogle Scholar
  13. 13.
    Li D. Y., B. Brooke, E. C. Davis, R. P. Mecham, L. K. Sorensen, B. B. Boak, E. Eichwald, M. T. Keating 1998 Elastin is an essential determinant of arterial morphogenesis. Nature. 393:276–280PubMedCrossRefGoogle Scholar
  14. 14.
    Li S., W. N. McDicken, P. R. Hoskins 1993 Blood vessel diameter measurement by ultrasound. Physiol. Meas. 14:291–297PubMedCrossRefGoogle Scholar
  15. 15.
    McCulloch A. D., A. B. Harris, C. E. Sarraf, M. Eastwood 2004 New multi-cue bioreactor for tissue engineering of tubular cardiovascular samples under physiological conditions. Tissue Eng. 10:565–573PubMedCrossRefGoogle Scholar
  16. 16.
    Mironov V., V. Kasyanov, K. McAllister, S. Oliver, J. Sistino, R. Markwald 2003 Perfusion bioreactor for vascular tissue engineering with capacities for longitudinal stretch. J. Craniofac. Surg. 14:340–347PubMedCrossRefGoogle Scholar
  17. 17.
    Motlagh, D., J. Allen, R. Hoshi, J. Yang, K. Lui, and G. A. Ameer. Hemocompatibility evaluation of poly(diol citrate) in vitro for vascular tissue engineering. J. Biomed. Mat. Res. A. Accepted, 2007, doi 10.1002/jbm.a.31211.Google Scholar
  18. 18.
    Narita Y., K. Hata, H. Kagami, A. Usui, M. Ueda, Y. Ueda 2004 Novel pulse duplicating bioreactor system for tissue-engineered vascular construct. Tissue Eng. 10:1224–1233PubMedGoogle Scholar
  19. 19.
    Niklason L. E., W. Abbott, J. Gao, B. Klagges, K. Hirschi, K. Ulubayram, N. Conroy, R. Jones, A. Vasanwala, S. Sanzgiri, R. Langer 2001 Morphologic and mechanical characteristics of engineered bovine arteries. J. Vasc. Surg. 33:628–638PubMedCrossRefGoogle Scholar
  20. 20.
    Niklason L. E., J. Gao, W. M. Abbott, K. K. Hirschi, S. Houser, R. Marini, R. Langer 1999 Functional arteries grown in vitro. Science 284:489–493PubMedCrossRefGoogle Scholar
  21. 21.
    Ojha M. 1994 Wall shear stress temporal gradient and anastomotic intimal hyperplasia. Circ. Res. 74:1227–1231PubMedGoogle Scholar
  22. 22.
    Olbrich T., A. Murray 2004 Assessment of a technique to determine the mechanical properties of coronary arteries using mock arteries. Physiol. Meas. 25:997–1011PubMedCrossRefGoogle Scholar
  23. 23.
    Seliktar D., R. A. Black, R. Vito, R. M. Nerem 2000 Dynamic mechanical conditioning of collagen-gel blood vessel constructs induces remodeling in vitro. Ann. Biomed. Eng. 28:351–362PubMedCrossRefGoogle Scholar
  24. 24.
    Seliktar D., R. M. Nerem, Z. S. Galis 2001 The role of matrix metalloproteinase-2 in the remodeling of cell-seeded vascular constructs subjected to cyclic strain. Ann. Biomed. Eng. 29:923–934PubMedCrossRefGoogle Scholar
  25. 25.
    Sodian R., T. Lemke, C. Fritsche, S. P. Hoerstrup, P. Fu, E. V. Potapov, H. Hausmann, R. Hetzer 2002 Tissue-engineering bioreactors: A new combined cell-seeding and perfusion system for vascular tissue engineering. Tissue Eng. 8:863–870PubMedCrossRefGoogle Scholar
  26. 26.
    Sonoda H., K. Takamizawa, Y. Nakayama, H. Yasui, T. Matsuda 2001 Small-diameter compliant arterial graft prosthesis: Design concept of coaxial double tubular graft and its fabrication. J. Biomed. Mater. Res. 55:266–276PubMedCrossRefGoogle Scholar
  27. 27.
    Sonoda H., S. Urayama, K. Takamizawa, Y. Nakayama, C. Uyama, H. Yasui, T. Matsuda 2002 Compliant design of artificial graft: Compliance determination by new digital x-ray imaging system-based method. J. Biomed. Mater. Res. 60:191–195PubMedCrossRefGoogle Scholar
  28. 28.
    Stewart S. F., D. J. Lyman 1992 Effects of a vascular graft/natural artery compliance mismatch on pulsatile flow. J. Biomech. 25:297–310PubMedCrossRefGoogle Scholar
  29. 29.
    Tai N. R., H. J. Salacinski, A. Edwards, G. Hamilton, A. M. Seifalian 2000 Compliance properties of conduits used in vascular reconstruction. Brit. J. Surg. 87:1516–1524PubMedCrossRefGoogle Scholar
  30. 30.
    Thompson W. 2002 Reflection of the pathogenesis of abdominal aortic aneurysms. Cardiovasc. Surg. 10:389–394PubMedCrossRefGoogle Scholar
  31. 31.
    Tiwari A., H. Salacinski, A. M. Seifalian, G. Hamilton 2002 New prostheses for use in bypass grafts with special emphasis on polyurethanes. Cardiovasc Surg. 10:191–197PubMedCrossRefGoogle Scholar
  32. 32.
    Wasef B., B. Baxter, R. Chisholm, R. Dalman, M. Fillinger, J. Heinecke, J. Humphrey, H. Kuivaniemi, W. Parks, W. Pearce, C. Platsoucas, G. Sukhova, R. Thompson, D. Tilson, C. Zarins 2001 Pathogenesis of abdominal aortic aneurysms: A multidisciplinary research program supported by the national heart, lung, and blood institute. J. Vasc. Surg. 34:730–738CrossRefGoogle Scholar
  33. 33.
    Yang J., D. Motlagh, J. B. Allen, A. R. Webb, M. R. Kibbe, O. Aalami, M. Kapadia, T. J. Carroll, G. A. Ameer 2006 Modulating expanded polytetrafluoroethylene vascular graft host response via citric acid-based biodegradable elastomers. Adv. Mater. 18:1493–1498CrossRefGoogle Scholar
  34. 34.
    Yang J., D. Motlagh, A. Webb, G. A. Ameer 2005 A novel biphasic elastomeric scaffold for small-diameter blood vessel tissue engineering. Tissue Eng. 11:1876–1886PubMedCrossRefGoogle Scholar
  35. 35.
    Yang J., A. Webb, G. Ameer 2004 Novel citric acid-based biodegradable elastomers for tissue engineering. Adv. Mater. 16:511–516CrossRefGoogle Scholar
  36. 36.
    Yang J., A. Webb, S. Pickerill, G. Hageman, G. A. Ameer 2006 Synthesis and evaluation of novel biodegradable elastomeric polyesters. Biomaterials 27:1889–1898PubMedCrossRefGoogle Scholar
  37. 37.
    Zhuang Y. J., T. M. Singh, C. K. Zarins, H. Masuda 1998 Sequential increases and decreases in blood flow stimulates progressive intimal thickening. Eur. J. Vasc. Endovasc. 16:301–310CrossRefGoogle Scholar

Copyright information

© Biomedical Engineering Society 2007

Authors and Affiliations

  • Antonio R. Webb
    • 1
  • Bryan D. Macrie
    • 1
  • Ananda S. Ray
    • 1
  • Jack E. Russo
    • 1
  • Andrew M. Siegel
    • 1
  • Matthew R. Glucksberg
    • 1
  • Guillermo A. Ameer
    • 1
  1. 1.Biomedical Engineering DepartmentNorthwestern UniversityEvanstonUSA

Personalised recommendations