A novel composite scaffold for cardiac tissue engineering

  • Hyoungshin Park
  • Milica Radisic
  • Jeong Ok Lim
  • Bong Hyun Chang
  • Gordana Vunjak-Novakovic
Articles Biotechnology

Summary

One approach to the engineering of functional cardiac tissue for basic studies and potential clinical use involves bioreactor cultivation of dissociated cells on a biomaterial scaffold. Our objective was to develop a scaffold that is (1) highly porous with large intereconnected pores (to facilitate mass transport), (2) hydrophilic (to enhance cell attachment), (3) structurally stable (to withstand the shearing forces during bioreactor cultivation), (4) degradable (to provide ultimate biocompatibility of the tissue graft), and (5) elastic (to enable transmission of contractile forces). The scaffold of choice was made as a composite of poly(Dl-lactide-co-caprolactone), poly(Dl-lactide-co-glycolide) (PLGA), and type I collagen, with open interconnected pores and the average void volume of 80±5%. Neonatal rat heart cells suspended in Matrigel were seeded into the scaffold at a physiologically high density (1.35×108 cells/cm3) and cultivated for 8 d in cartridges perfused with culture medium or in orbitally mixed dishes (25 rpm); collagen sponge (Ultrafoam⋆m) and PLGA sponge served as controls. Construct cellularity, presence of cardiac markers, and contractile properties were markedly improved in composite scaffolds as compared with both controls.

Key words

cardiac myocyte collagen caprolactone PLGA biocompatibility perfusion 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Agrawal, C. M.; Gabriele, P. E.; Niederauer, G.; Athanasiou, K. A. Fabrication and characterization of pla-pga orthopedic implants. Tissue Eng. 1:241–252; 1995.CrossRefGoogle Scholar
  2. Akins, R. E. Can tissue engineering mend broken hearts? Circ. Res. 90:120–122; 2002.PubMedGoogle Scholar
  3. Bader, A.; Schilling, T.; Teebken, O. E.; Brandes, G.; Herden, T.; Steinhoff, G.; Haverich, A. Tissue engineering of heart valves—human endothelial cell seeding of detergent acellularized porcine valves. Eur. J. Cardiothorac. Surg. 14:279–284; 1998.PubMedCrossRefGoogle Scholar
  4. Bursac, N.; Papadaki, M.; Cohen, R. J.; Schoen, F. J.; Eisenberg, S. R.; Carrier, R.; Vunjak-Novakovic, G.; Freed, L. E. Cardiac muscle tissue engineering: toward an in vitro model for electrophysiological studies. Am. J. Physiol. Heart Circ. Physiol. 277:H433-H444; 1999.Google Scholar
  5. Carrier, R. L.; Papadaki, M.; Rupnick, M.; Schoen, F. J.; Bursac, N.; Langer, R.; Freed, L. E.; Vunjak-Novakovic, G. Cardiac tissue engineering: cell seeding, cultivation parameters and tissue construct characterization. Biotechnol. Bioeng. 64:580–589; 1999.PubMedCrossRefGoogle Scholar
  6. Cima, L. G.; Vacanti, J. P.; Vacanti, C.; Ingber, D.; Mooney, D.; Langer, R. Tissue engineering by cell transplantation using degradable polymer substrates. J. Biomech. Eng. 113:143–151; 1991.PubMedGoogle Scholar
  7. Dai, N. T.; Williamson, M. R.; Khammo, N.; Adams, E. F.; Coombes, A. G. Composite cell support membranes based on collagen and polycaprolactone for tissue engineering of skin. Biomaterials 25:4263–4271; 2004.PubMedCrossRefGoogle Scholar
  8. Dohmen, P. M.; Lembcke A.; Hots, H.; Kivelitz, D.; Konertz, W. F.: Ross operation with a tissue engineered heart valve. Ann. Thorac. Surg. 74:1438–1442; 2002.PubMedCrossRefGoogle Scholar
  9. Freed, L. E.; Vunjak-Novakovic, G. Culture of organized cell communities. Adv. Drug Deliv. Rev. 33:15–30; 1998.PubMedCrossRefGoogle Scholar
  10. Freed, L. E.; Vunjak-Novakovic, G.: Tissue engineering bioreactors. In: Lanza, R. P.; Langer, R.; Vacanti, J., ed. Principles of tissue engineering, 2nd ed. San Diego, CA: Academic Press; 2000:143–156.Google Scholar
  11. Hua, F. J.; Kim, G. E.; Lee, J. D.; Son, Y. K.; Lee, D. S. Macroporous poly(llactide) scaffold 1. Preparation of macroporous scaffold by liquidliquid phase separation of a PLLA-dioxane-water system. J. Biomed. Mater. Res. 63:161–167; 2002.PubMedCrossRefGoogle Scholar
  12. Ishaug-Riley, S. L.; Crane, G. M.; Gurlek, A.; Miller, M. J.; Yasko, A. W.; Yaszemski, M. J.; Mikos, A. G. Ectopic bone formation by marrow stromal osteoblast transplantation using poly(Dl-lactic-co-glycolic acid) foams implanted into the rat mesentery. J. Biomed. Mater. Res. 36:1–8; 1997.PubMedCrossRefGoogle Scholar
  13. Krupnick, A. S.; Kreisel, D.; Engels, F. H.; Szeto, W. Y.; Plappert, T.; Popmaa, S. H. Flake, A. W.; Rosengard, B. R. A novel small animal model of left ventricular tissue engineering. J. Heart Lung Transplant. 21:233–243; 2002.PubMedCrossRefGoogle Scholar
  14. Lee, C. H.; Singla, A.; Lee, Y. Biomedical application of collagen. Int. J. Pharm. 221:1–22; 2001.PubMedCrossRefGoogle Scholar
  15. Leor, J.; Aboulafia-Etzion, S.; Dar, A.; Shapiro, L.; Barbash, I. M.; Battler, A.; Granot, Y.; Cohen, S. Bioengineered cardiac grafts: a new approach to repair the infarcted myocardium? Circulation 102:III56-III61; 2000.PubMedGoogle Scholar
  16. Orlic, D.; Kajstura, J.; Chimenti, S., et al. Bone marrow cells regenerate infarcted myocardium. Nature 410:701–705; 2001.PubMedCrossRefGoogle Scholar
  17. Ozawa, T.; Mickle, D. A.; Weisel, R. D.; Koyama, N.; Ozawa, S.; Li, R. K. Optimal biomaterial for creation of autologous cardiac grafts. Circulation 106:1176–1182; 2002.CrossRefGoogle Scholar
  18. Papadaki, M.; Bursac, N.; Langer, R.; Merok, J.; Vunjak-Novakovic, G.; Freed, L. E. Tissue engineering of functional cardiac muscle: molecular, structural and electrophysiological studies. Am. J. Physiol. Heart Circ. Physiol. 280:H168-H178; 2001.PubMedGoogle Scholar
  19. Radisic, M.; Euloth, M.; Yang, L.; Langer, R.; Freed, L. E.; Vunjak-Novakovic, G. High density seeding of myocyte cells for tissue engineering. Biotechnol. Bioeng. 82:403–414; 2003.PubMedCrossRefGoogle Scholar
  20. Radisic, M.; Park, H.; Shing, H.; Consi, T.; Schoen, F. J.; Langer, R.; Freed, L. E.; Vunjak-Novakovic, G. Functional assembly of engineered myocardium by electrical stimulation of cardiac myocytes cultured on scaffolds. Proc. Natl. Acad. Sci. USA 101:18129–18134, 2004a.PubMedCrossRefGoogle Scholar
  21. Radisic, M.; Yang, L.; Boublik, J.; Cohen, R. J.; Langer, R.; Freed, L. E.; Vunjak-Novakovic, G. Medium perfusion enables engineering of compact and contractile cardiac tissue. Am. J. Physiol. Heart Circ. Physiol. 286:H507-H516; 2004b.PubMedCrossRefGoogle Scholar
  22. Radisic, M.; Obradovic, B.; Vunjak-Novakovic, G. Functional tissue engineering of cartilage and myocardium: bioreactor aspects. In: Ma, P. X.; Eliseeff, J., ed. Scaffolding in tissue engineering. Marcel Dekker; pp 491–520, 2005.Google Scholar
  23. Shinoka, T.; Breuer, C. K.; Tanel, R. E., et al. Tissue engineering heart valves: valve leaflet replacement study in a lamb model. Ann. Thorac. Surg. 60:S513-S516; 1995.PubMedCrossRefGoogle Scholar
  24. Shirota, T.; Yasui, H.; Shimokawa, H.; Matsuda, T. Fabrication of endothelial progenitor cell (EPC)-seeded intravascular stent devices and in vitro endothelialization on hybrid vascular tissue. Biomaterials 24:2295–2302; 2003.PubMedCrossRefGoogle Scholar
  25. Sodian, R.; Hoerstrup, S. P.; Sperling, J. S.; Daebritz, S. H.; Martin, D. P.; Schoen, F. J.; Vacanti, J. P.; Mayer, J. E. Tissue engineering of heart valves: in vitro experiences. Ann. Thorac. Surg. 70:140–144; 2000.PubMedCrossRefGoogle Scholar
  26. Woodward, S. C.; Brewer, P. S.; Moatamed, F.; Schindler, A.; Pitt, C. G. The intracellular degradation of poly(epsilon-caprolactone). J. Biomed. Mater. Res. 19:437–444; 1985.PubMedCrossRefGoogle Scholar
  27. Zimmermann, W. H.; Eschenhagen, T. Cardiac tissue engineering for replacement therapy. Heart Fail. Rev. 8:259–269; 2003.PubMedCrossRefGoogle Scholar

Copyright information

© Society for In Vitro Biology 2005

Authors and Affiliations

  • Hyoungshin Park
    • 1
  • Milica Radisic
    • 1
  • Jeong Ok Lim
    • 2
    • 3
  • Bong Hyun Chang
    • 4
  • Gordana Vunjak-Novakovic
    • 1
  1. 1.Harvard-MIT Division of Health Sciences and TechnologyMassachusetts Institute of TechnologyCambridge
  2. 2.Medical Research InstituteKyungpook National UniversityDaeguKorea
  3. 3.Institute for Regenerative MedicineWake Forest School of MedicineWinston Salem
  4. 4.Department of Thoracic and cardiovascular SurgeryKyungpook National University, School of MedicineDaeguKorea

Personalised recommendations