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Inflammatory Response Assessment of a Hybrid Tissue-Engineered Heart Valve Leaflet

Abstract

Despite substantial research in the past few decades, only slight progress has been made toward developing biocompatible, tissue-engineered scaffolds for heart valve leaflets that can withstand the dynamic pressure inside the heart. Recent progress on the development of hybrid scaffolds, which are composed of a thin metal mesh enclosed by multi-layered tissue, appear to be promising for heart valve engineering. This approach retains all the advantages of biological scaffolds while developing a strong extracellular matrix backbone to withstand dynamic loading. This study aims to test the inflammatory response of hybrid tissue-engineered leaflets based on characterizing the activation of macrophage cells cultured on the surfaces of the tissue construct. The results indicate that integration of biological layers around a metal mesh core—regardless of its type—may reduce the evoked inflammatory responses by THP-1 monocyte-like cells. This observation implies that masking a metal implant within a tissue construct prior to implantation can hide it from the immune system and may improve the implant’s biocompatibility.

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Notes

  1. EPI: end per inch; PPI: pick per inch.

References

  1. Alavi, S. H., and A. Kheradvar. Metal mesh scaffold for tissue engineering of membranes. Tissue Eng. Part C Methods 18:293–301, 2011.

    PubMed  Article  Google Scholar 

  2. Anderson, J. M. Inflammatory response to implants. ASAIO J. 34:101, 1988.

    Article  CAS  Google Scholar 

  3. Anderson, J. M., A. Rodriguez, and D. T. Chang. Foreign body reaction to biomaterials. Semin. Immunol. 20:86–100, 2008.

    PubMed  Article  CAS  Google Scholar 

  4. Apte, S. S., A. Paul, S. Prakash, and D. Shum-Tim. Current developments in the tissue engineering of autologous heart valves: moving towards clinical use. Futur. Cardiol. 7:77–97, 2011.

    Article  Google Scholar 

  5. Auwerx, J. The human leukemia cell line, THP-1: a multifacetted model for the study of monocyte-macrophage differentiation. Cell. Mol. Life Sci. 47:22–31, 1991.

    Article  CAS  Google Scholar 

  6. Boontheekul, T., and D. J. Mooney. Protein-based signaling systems in tissue engineering. Curr. Opin. Biotechnol. 14:559–565, 2003.

    PubMed  Article  CAS  Google Scholar 

  7. Breuer, C. K., B. A. Mettler, T. Anthony, V. L. Sales, F. J. Schoen, and J. E. Mayer. Application of tissue-engineering principles toward the development of a semilunar heart valve substitute. Tissue Eng. 10:1725–1736, 2004.

    PubMed  Article  CAS  Google Scholar 

  8. Butcher, J. T., and R. M. Nerem. Porcine aortic valve interstitial cells in three-dimensional culture: comparison of phenotype with aortic smooth muscle cells. J. Heart Valve Dis. 13:478–486, 2004.

    PubMed  Google Scholar 

  9. Butcher, J. T., A. M. Penrod, A. J. García, and R. M. Nerem. Unique morphology and focal adhesion development of valvular endothelial cells in static and fluid flow environments. Arterioscler. Thromb. Vasc. Biol. 24:1429–1434, 2004.

    PubMed  Article  CAS  Google Scholar 

  10. Chester, A. H., and P. M. Taylor. Molecular and functional characteristics of heart-valve interstitial cells. Philos. Trans. R. Soc. B: Biol. Sci. 362:1437–1443, 2007.

    Article  CAS  Google Scholar 

  11. Filip, D., A. Radu, and M. Simionescu. Interstitial cells of the heart valves possess characteristics similar to smooth muscle cells. Circ. Res. 59:310–320, 1986.

    PubMed  Article  CAS  Google Scholar 

  12. Flanagan, T. C., and A. Pandit. Living artificial heart valve alternatives: a review. Eur. Cell Mater. 6:28–45, 2003.

    PubMed  CAS  Google Scholar 

  13. Frankenberger, M., A. Pforte, T. Sternsdorf, B. Passlick, P. Baeuerle, and H. Ziegler-Heitbrock. Constitutive nuclear NF-kappa B in cells of the monocyte lineage. Biochem. J. 304:87, 1994.

    PubMed  CAS  Google Scholar 

  14. Grande-Allen, K., and J. Liao. The heterogeneous biomechanics and mechanobiology of the mitral valve: implications for tissue engineering. Curr. Cardiol. Rep. 13:113–120.

  15. Hammermeister, K. E., G. K. Sethi, W. G. Henderson, C. Oprian, T. Kim, and S. Rahimtoola. A comparison of outcomes in men 11 years after heart-valve replacement with a mechanical valve or bioprosthesis. N. Engl. J. Med. 328:1289–1296, 1993.

    PubMed  Article  CAS  Google Scholar 

  16. Heil, T., K. Volkmann, J. Wataha, and P. Lockwood. Human peripheral blood monocytes versus THP-1 monocytes for in vitro biocompatibility testing of dental material components. J. Oral Rehabil. 29:401–407, 2002.

    PubMed  Article  CAS  Google Scholar 

  17. Hoerstrup, S. P., R. Sodian, S. Daebritz, J. Wang, E. A. Bacha, D. P. Martin, A. M. Moran, K. J. Guleserian, J. S. Sperling, S. Kaushal, J. P. Vacanti, F. J. Schoen, and J. E. Mayer, Jr. Functional living trileaflet heart valves grown in vitro. Circulation 102(III):44–49, 2000.

    Google Scholar 

  18. Klinger, A., D. Steinberg, D. Kohavi, and M. Sela. Mechanism of adsorption of human albumin to titanium in vitro. J. Biomed. Mater. Res. 36:387–392, 1997.

    PubMed  Article  CAS  Google Scholar 

  19. Lee, S., F. Brennan, J. Jacobs, R. Urban, D. Ragasa, and T. Glant. Human monocyte/macrophage response to cobalt-chromium corrosion products and titanium particles in patients with total joint replacements. J. Orthop. Res. 15:40–49, 1997.

    PubMed  Article  CAS  Google Scholar 

  20. Liu, W. F., M. Ma, K. M. Bratlie, T. T. Dang, R. Langer, and D. G. Anderson. Real-time in vivo detection of biomaterial-induced reactive oxygen species. Biomaterials 32:1796–1801, 2011.

    PubMed  Article  Google Scholar 

  21. Lynn, A., I. Yannas, and W. Bonfield. Antigenicity and immunogenicity of collagen. J. Biomed. Mater. Res. B Appl. Biomater. 71:343–354, 2004.

    PubMed  Article  CAS  Google Scholar 

  22. Ma, M., W. F. Liu, P. S. Hill, K. M. Bratlie, D. J. Siegwart, J. Chin, M. Park, J. Guerreiro, and D. G. Anderson. Development of cationic polymer coatings to regulate foreign‐body responses. Adv. Mater. 2011.

  23. Mendelson, K., and F. Schoen. Heart valve tissue engineering: concepts, approaches, progress, and challenges. Ann. Biomed. Eng. 34:1799–1819, 2006.

    PubMed  Article  Google Scholar 

  24. Rabkin, E., and F. J. Schoen. Cardiovascular tissue engineering. Cardiovasc. Pathol. 11:305–317, 2002.

    PubMed  Article  Google Scholar 

  25. Rabkin-Aikawa, E., J. E. Mayer, Jr., and F. J. Schoen. Heart valve regeneration. Adv. Biochem. Eng. Biotechnol. 94:141–179, 2005.

    PubMed  Google Scholar 

  26. Ryhänen, J. Biocompatibility evaluation of nickel-titanium shape memory metal alloy. Oulun yliopisto, 1999.

  27. Sacks, M. S., F. J. Schoen, and J. E. Mayer. Bioengineering challenges for heart valve tissue engineering. Annu. Rev. Biomed. Eng. 11:289–313, 2009.

    PubMed  Article  CAS  Google Scholar 

  28. Schoen, F. J., and R. J. Levy. Tissue heart valves: current challenges and future research perspectives. J. Biomed. Mater. Res. 47:439–465, 1999.

    PubMed  Article  CAS  Google Scholar 

  29. Shah, S. R., and N. R. Vyavahare. The effect of glycosaminoglycan stabilization on tissue buckling in bioprosthetic heart valves. Biomaterials 29:1645–1653, 2008.

    PubMed  Article  CAS  Google Scholar 

  30. Shinoka, T., C. K. Breuer, R. E. Tanel, G. Zund, T. Miura, P. X. Ma, R. Langer, J. P. Vacanti, and J. E. Mayer, Jr. Tissue engineering heart valves: valve leaflet replacement study in a lamb model. Ann. Thorac. Surg. 60:S513–S516, 1995.

    PubMed  Article  CAS  Google Scholar 

  31. Shinoka, T., P. X. Ma, D. Shum-Tim, C. K. Breuer, R. A. Cusick, G. Zund, R. Langer, J. P. Vacanti, and J. E. Mayer, Jr. Tissue-engineered heart valves. Autologous valve leaflet replacement study in a lamb model. Circulation 94:164–168, 1996.

    Google Scholar 

  32. Steinhoff, G., U. Stock, N. Karim, H. Mertsching, A. Timke, R. R. Meliss, K. Pethig, A. Haverich, and A. Bader. Tissue engineering of pulmonary heart valves on allogenic acellular matrix conduits: in vivo restoration of valve tissue. Circulation 102(III):50–55, 2000.

    Google Scholar 

  33. Stephens, E. H., N. de Jonge, M. P. McNeill, C. A. Durst, and K. J. Grande-Allen. Age-related changes in material behavior of porcine mitral and aortic valves and correlation to matrix composition. Tissue Eng. Part A 16:867–878, 2009.

    Article  Google Scholar 

  34. Syedain, Z. H., and R. T. Tranquillo. Controlled cyclic stretch bioreactor for tissue-engineered heart valves. Biomaterials 30:4078–4084, 2009.

    PubMed  Article  CAS  Google Scholar 

  35. Thierry, B., M. Tabrizian, C. Trepanier, O. Savadogo, and L. H. Yahia. Effect of surface treatment and sterilization processes on the corrosion behavior of NiTi shape memory alloy. J. Biomed. Mater. Res. 51:685–693, 2000.

    PubMed  Article  CAS  Google Scholar 

  36. Tsuchiya, S., Y. Kobayashi, Y. Goto, H. Okumura, S. Nakae, T. Konno, and K. Tada. Induction of maturation in cultured human monocytic leukemia cells by a phorbol diester. Cancer Res. 42:1530, 1982.

    PubMed  CAS  Google Scholar 

  37. van Geemen, D., P. Riem Vis, S. Soekhradj-Soechit, J. Sluijter, M. de Liefde-van Beest, J. Kluin, and C. Bouten. Decreased mechanical properties of heart valve tissue constructs cultured in platelet lysate as compared to fetal bovine serum. Tissue Eng. Part C Methods 7:607–617, 2011.

    Article  Google Scholar 

  38. Vesely, I. Heart valve tissue engineering. Circ. Res. 97:743–755, 2005.

    PubMed  Article  CAS  Google Scholar 

  39. Vince, D. G., J. A. Hunt, and D. F. Williams. Quantitative assessment of the tissue response to implanted biomaterials. Biomaterials 12:731–736, 1991.

    PubMed  Article  CAS  Google Scholar 

  40. Wataha, J., P. Lockwood, M. Marek, and M. Ghazi. Ability of Ni-containing biomedical alloys to activate monocytes and endothelial cells in vitro. J. Biomed. Mater. Res. 45:251–257, 1999.

    PubMed  Article  CAS  Google Scholar 

  41. Wataha, J. C., S. Ratanasathien, C. T. Hanks, and Z. Sun. In vitro IL-1 [beta] and TNF-[alpha] release from THP-1 monocytes in response to metal ions. Dent. Mater. 12:322–327, 1996.

    PubMed  Article  CAS  Google Scholar 

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Acknowledgments

This work is partially supported by a Coulter Translational Research Award (CTRA) by the Wallace H. Coulter Foundation and a seed grant from the Edwards Lifesciences Center for Advanced Cardiovascular Technology at UC Irvine that was provided to Dr. Kheradvar.

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Correspondence to Arash Kheradvar.

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Associate Editor Jane Grande-Allen oversaw the review of this article.

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Alavi, S.H., Liu, W.F. & Kheradvar, A. Inflammatory Response Assessment of a Hybrid Tissue-Engineered Heart Valve Leaflet. Ann Biomed Eng 41, 316–326 (2013). https://doi.org/10.1007/s10439-012-0664-7

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  • DOI: https://doi.org/10.1007/s10439-012-0664-7

Keywords

  • Hybrid heart valve
  • THP-1 cell line
  • Inflammatory response
  • Metal mesh scaffold