Skip to main content
SpringerLink
Log in

Silk fibroin-Pellethane® cardiovascular patches: Effect of silk fibroin concentration on vascular remodeling in rat model

  • Tissue Engineering Constructs and Cell Substrates
  • Original Research
  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

Life-threatening cardiovascular anomalies require surgery for structural repair with cardiovascular patches. The biomaterial patch, derived from Bombyx mori silk fibroin (SF), is used as an alternative material due to its excellent tissue affinity and biocompatibility. However, SF lacks the elastomeric characteristics required for a cardiovascular patch. In order to overcome this shortcoming, we combined the thermoplastic polyurethane, Pellethane® (PU) with SF to develop an elastic biocompatible patch. Therefore, the purpose of this study was to investigate the feasibility of the blended SF/PU patch in a vascular model. Additionally, we focused on the effects of different SF concentrations in the SF/PU patch on its biological and physical properties. Three patches of different compositions (SF, SF7PU3 and SF4PU6) were created using an electrospinning method. Each patch type (n = 18) was implanted into rat abdominal aorta and histopathology was assessed at 1, 3, and 6 months post-implantation. The results showed that with increasing SF content the tensile strength and elasticity decreased. Histological evaluation revealed that inflammation gradually decreased in the SF7PU3 and SF patches throughout the study period. At 6 months post-implantation, the SF7PU3 patch demonstrated progressive remodeling, including significantly higher tissue infiltration, elastogenesis and endothelialization compared with SF4PU6. In conclusion, an increase of SF concentration in the SF/PU patch had effects on vascular remodeling and physical properties. Moreover, our blended patch might be an attractive alternative material that could induce the growth of a neo-artery composed of tissue present in native artery.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Kazuro L, Fujimoto MD, Jianjun G, Hideki O, Tetsuro S, William RW. In vivo evaluation of a porous, elastic, biodegradable patch for reconstructive cardiac procedures. Ann Thorac Surg. 2007;83:648–54.

    Article  Google Scholar 

  2. Igor T, Sava K, Tanja M, Omke T, Christoph B, Andres H, Axel H, Serghei C. Viable vascularized autologous patch for transmural myocardial reconstruction. Eur J Cardio Thorac Surg. 2009;36:306–11.

    Article  Google Scholar 

  3. David K, Emile B. New Technologies for surgery of the congenital cardiac defect. Rambam Maimonides Med J. 2013;4:1–14.

    Google Scholar 

  4. Seokwon P, Jeffrey GJ. Biomaterials advances in patches for congenital heart defect repair. J. of Cardiovasc. Trans. Res. 2011;4:646–54.

    Article  Google Scholar 

  5. Sakai T, Li RK, Weisel RD, Mickle DA, Kim ETJ, Jia ZQ, Yau TM. The fate of a tissue engineered cardiac graft in the right ventricular outflow tract of the rat. J Thorac Cardiovasc Surg. 2001;121:932–42.

    Article  Google Scholar 

  6. Charu V, David LK. Silk as biomaterial. Prog. Polym. Sci. 2007;32:991–1007.

    Article  Google Scholar 

  7. Altman GH, Diaz F, Jakuba C, Calabro T, Horan RL, Chen J, Lu H, Richmond J, Kaplan DL. Silk-based biomaterials. Biomaterials. 2003;24:401–16.

    Article  Google Scholar 

  8. Banani K, Rangam R, Subhas CK, Xungai W. Silk fibroin biomaterials for tissue regenerations. Adv Drug Deliv Rev. 2013;65:457–70.

    Article  Google Scholar 

  9. Meinel L, Kaplan D. Silk constructs for delivery of musculoskeletal therapeutics. Adv Drug Deliv Rev. 2012;12:1111–22.

    Article  Google Scholar 

  10. Omenetto FG, Kaplan DL. New opportunities for ancient material. Science. 2010;329:528–31.

    Article  Google Scholar 

  11. Yang M, Yamauchi K, Kurokawa M, Asakura T. Design of silk-like biomaterials inspired by mussel-adhesive protein. Tissue Eng. 2007;13:2941–7.

    Article  Google Scholar 

  12. Higa K, Takeshima N, Moro F, Kawakita T, Kawashima M, Demura M, Shimazaki J, Asakura T, Tsubota K, Shimmura S. Porous silk fibroin film as a transparent carrier for cultivated corneal epithelial sheets. J Biomater Sci Polym Ed. 2011;22:2261–76.

    Article  Google Scholar 

  13. Nagano A, Tanioka Y, Sakurai N, Sezutsu H, Kuboyama N, Kiba H, Tanimoto Y, Nishiyama N, Asakura T. Regeneration of the femoral epicondyle on calcium-binding silk scaffolds developed using transgenic silk fibroin produced by transgenic silkworm. Acta Biomater. 2011;7:1192–201.

    Article  Google Scholar 

  14. Zhang X, Baughman CB, Kaplan DL. In vitro evaluation of electrospun silk fibroin scaffolds for vascular cell growth. Biomaterials 2008;29:2217–27.

    Article  Google Scholar 

  15. Handschel J, Meyer T, Wiesmann HP. Fundamentals of tissue engineering and regenerative medicine. New York: Springer; 2009.

    Google Scholar 

  16. Huang FH, Sun LZ, Zheng J. In vitro and in vivo characterization of a silk fibroin-coated polyester vascular prosthesis. Artif Organs. 2008;32:932–41.

    Article  Google Scholar 

  17. The Lubrizol Corporation (2017). Pellethane® TPU. (online) https://www.lubrizol.com/en/Life-Sciences/Products?Prllethane-TPU (Accessed 27 Aug 2017).

  18. Pinchuk L. A review of the biostability and carcinogenicity of polyurethanes in medicine and the new generation of biostable polyurethanes. J Biomater Sci Polymer Edn. 1994;6:225–67.

    Article  Google Scholar 

  19. Gunatillake PA, Adhikari R. Biodegradable synthetic polymers for tissue engineering. Eur Cell Mater. 2003;5:1–16.

    Article  Google Scholar 

  20. Stokes K, Mc Venes R, Anderson JM. Polyurethane elastomer biostability. J Biomater Appl. 1995;9(4):321–54.

    Article  Google Scholar 

  21. Jimenez G, Asai S, Shishido A, Sumita M. Effect of the soft segment on the fatique behavior of segmented polyurethanes. Eur Polym J. 2000;36(9):2039–50.

    Article  Google Scholar 

  22. Chen JH, Wei J, Chang C, Laiw RF, Lee YD. Studies on segmented polyurethane for biomedical application: Effects of composition and hard-segment content on biocompatibility. J Biomed Mater Res A. 1998;41(4):633–48.

    Article  Google Scholar 

  23. Bergmeister H, Schreiber C, Grasl C, Walter I, Plasenzotti R, Stoiber M, Schima H. Healing characteristics of electrospun polyurethane grafts with various porosities. Acta Biomater. 2013;9(4):6032–40.

    Article  Google Scholar 

  24. Chiarini A, Petrini P, Bozzini S, Pra ID, Armato U. Silk fibroin/poly(carbonate)-urethane as a substrate for cell growth: in vitro interactions with human cells. Biomaterials. 2003;24:789–99.

    Article  Google Scholar 

  25. Park HS, Gong MS, Park JH, Moon SI, Wall IB, Kim HW, Lee JH, Jonathan CK. Silk fibroin–polyurethane blends: Physical properties and effect of silk fibroin content on viscoelasticity, biocompatibility and myoblast differentiation. Acta Biomater. 2013;9:8962–71.

    Article  Google Scholar 

  26. Scott SM, Gaddy LR, Sahmel R, Hoffman H. A collagen coated vascular prosthesis. J Cardiovasc Surg. 1987;28:498–504.

    Google Scholar 

  27. Fukayama T, Takagi K, Tanaka R, Hatakeyama Y, Aytemiz D, Suzuki Y, Asakura T. Biological reaction to small-diameter vascular grafts made of silk fibroin implanted in the abdominal aortae of rats. Ann Vasc Surg. 2015;29:341–52.

    Article  Google Scholar 

  28. Soldani G, Losi P, Bernabei M, Burchielli S, Chiappino D, Kull S, Briganti E, Spiller D. Long term performance of small-diameter vascular grafts made of a poly(ether)urethane-polydimethylsiloxane semiinterpenetrating polymeric network. Biomaterials. 2010;31:2592–605.

    Article  Google Scholar 

  29. Wu HC, Wang TW, Kang PL, Tsuang YH, Sun JS, Lin FH. Coculture of endothelial and smooth muscle cells on a collagen membrane in the development of a small-diameter vascular graft. Biomaterials. 2007;28:1385–92.

    Article  Google Scholar 

  30. Ahmed M, Ramos TA, Damanik F, Le BQ, Wieringa P, Bennink M, Blitterswijk CV, Boer J, Moroni L. A combinatorial approach towards the design of nanofibrous scaffolds for chondrogenesis. Sci Rep. 2014;5:14804.

    Article  Google Scholar 

  31. Assoul N, Flaud P, Chaouat M, Letourneur D, Bataille I. Mechanical properties of rat thoracic and abdominal aortas. J Biomech. 2008;41(10):2227–36.

    Article  Google Scholar 

  32. Akhtar R, Sherratt MJ, Cruickshank JK, Derby B. Characterizing the elastic properties of tissue. Mater Today. 2011;14(3):96–105.

    Article  Google Scholar 

  33. Abé H, Hayashi K. Data book on mechanical properties of living cells, tissues, and organs. Tokyo: Springer; 1996.

    Book  Google Scholar 

  34. García-Herrera CM, Atienza JM, Rojo FJ, Claes E, Guinea GV, Celentano DJ, Burgos RL. Mechanical behaviour and rupture of normal and pathological human ascending aortic wall. Med Biol Eng Comput. 2012;50(6):559–66.

    Article  Google Scholar 

  35. Renna NF, de las Heras N, Miatello RM. Pathophysiology of vascular remodeling in hypertension. Int J Hyper. 2013;2013:1–7.

  36. Lamba NM, Woodhouse KA, Cooper SL. Polyurethanes Biomed Appl. CRC Press;1997. pp. 132–135.

  37. Rhodes NP, Bellón JM, Buján MJ, Soldani G, Hunt JA. Inflammatory response to a novel series of siloxane-crosslinked polyurethane elastomers having controlled biodegradation. J Mater Sci Mater Med. 2005;16:1207–11.

    Article  Google Scholar 

  38. Lemson MS, Tordoir JHM, Daemen MJAP, Kitslaar PJEHM. Intimal hyperplasia in vascular grafts. Eur J Vasc Endovasc Surg. 2000;19:336–50.

    Article  Google Scholar 

  39. Fukayama T, Ozai Y, Shimokawadoko H, Aytemiz D, Tanaka R, Machida N, Asakura T. Effect of fibroin sponge coating on in vivo performance of knitted silk small diameter vascular grafts. Organogenesis. 2015;11:137–151.

    Article  Google Scholar 

  40. Ombrellaro MP, Stevens SL, Sciarrotta J, Freeman MB, Goldman MH. Effect of endoluminal PTFE graft placement on cell proliferation, PDGF secretion, and intimal hyperplasia. J Surg Res. 1996;63:110–114.

    Article  Google Scholar 

  41. Fukunishi T, Best CA, Sugiura T, Shoji T, Yi T, Udelsman B, Ohst D, Ong CS, Zhang H, Shinoka T, Breuer CK, Johnson J, Hibino N. Tissue-Engineered Small Diameter Arterial Vascular Grafts from Cell-Free Nanofiber PCL/Chitosan Scaffolds in a Sheep Model. PloS ONE. 2016;11:e0158555.

    Article  Google Scholar 

  42. Danenberg HD, Welt FG, Walker M, Seifert P, Toegel GS, Edelman ER. Systemic inflammation induced by lipopolysaccharide increases neointimal formation after balloon and stent injury in rabbits. Circulation. 2002;105:2917–22.

    Article  Google Scholar 

  43. Patel A, Fine B, Sandig M, Mequanint K. Elastin biosynthesis: the missing link in tissue-engineered blood vessels. Cardiovasc Res. 2006;71:40–9.

    Article  Google Scholar 

  44. Faury G. Function–structure relationship of elastic arteries in evolution: from microfibrils to elastin and elastic fibres. Pathol Biol. 2001;49:310–25.

    Article  Google Scholar 

  45. Long JL, Tranquillo RT. Elastic fiber production in cardiovascular tissue-equivalents. Matrix Biol. 2003;22:339–50.

    Article  Google Scholar 

  46. Anidjar S, Dobrin PB, Eichorst M, Graham GP, Chejfec G. Correlation of inflammatory infiltrate with the enlargement of experimental aortic aneurysms. J Vasc Surg. 1992;16:139–47.

    Article  Google Scholar 

  47. ZENA Werb, Banda, Jones MJ. PA. Degradation of connective tissue matrices by macrophages. J Exp Med. 1980;152:1537–53.

    Article  Google Scholar 

  48. Pearson JD. Endothelial cell function and thrombosis. Bailieres Best Pract Res Clin Haematol. 1999;12:329–41.

    Article  Google Scholar 

  49. Narayan D, Venkatraman SS. Effect of pore size and interpore distance on endothelial cell growth on polymers. J Biomed Mater Res A. 2008;87:710–8.

    Article  Google Scholar 

  50. Noishiki Y, Tomizawa Y, Yamane Y, Matsumoto A. Autocrine angiogenic vascular prosthesis with bone marrow transplantation. Nat Med. 1996;2:90–3.

    Article  Google Scholar 

  51. Khan OF, Sefton MV. Endothelialized biomaterials for tissue engineering applications in vivo. Trend Biotechnol. 2011;29:379–87.

    Article  Google Scholar 

  52. Hayabuchi Y, Mori K, Kitagawa T, Sakata M, Kagami S. Polytetrafluoroethylene graft calcification in patients with surgically repaired congenital heart disease: evaluation using multidetector-row computed tomography. Am Heart J. 2007;153(806):e1–e8.

    Google Scholar 

  53. Park JC, Song MJ, Hwang YS, Suh H. Calcification comparison of polymers for vascular graft. Yonsei Med J. 2001;42:304–10.

    Article  Google Scholar 

  54. Soldani G, Panol G, Sasken HF, Goddard MB, Galletti PM. Small diameter polyurethane-polydimethylsiloxane vascular prostheses made by a spraying, phase-inversion process. J Mater Sci Mater Med. 1992;3:106–13.

    Article  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Professor Dr. Noboru Machida and Professor Dr. Tetsuo Asakura for providing us with the histological facility and the imaging analysis system. We are also grateful to Dr. Tsunenori Kameda and Dr. Taiyo Yoshioka for providing us with the tensile testing machine. This project is entrusted to us by MAFF as part of Scientific technique research promotion program of agriculture, forestry, fishers and food industry (26051A). And, some of achievements were result from supports of grant, KAKENHI, from Grant-in-Aid for Scientific Research (15H03020) by Ministry of Education, Culture, Sports, Science and Technology Japan.

Author information

Authors and Affiliations

  1. Department of Veterinary Surgery, Tokyo University of Agriculture and Technology, Fuchu, 183-8509, Tokyo, Japan

    Pinkarn Chantawong, Takashi Tanaka, Akiko Uemura, Kazumi Shimada & Ryou Tanaka

  2. Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Koganei, 184-8588, Tokyo, Japan

    Akira Higuchi, Hirokazu Tajiri, Kohta Sakura & Yasumoto Nakazawa

  3. Department of Veterinary Toxicology, Tokyo University of Agriculture and Technology, Fuchu, 183-8509, Tokyo, Japan

    Tomoaki Murakami

Authors
  1. Pinkarn Chantawong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takashi Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Akiko Uemura
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kazumi Shimada
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Akira Higuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hirokazu Tajiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kohta Sakura
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tomoaki Murakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yasumoto Nakazawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ryou Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yasumoto Nakazawa or Ryou Tanaka.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chantawong, P., Tanaka, T., Uemura, A. et al. Silk fibroin-Pellethane® cardiovascular patches: Effect of silk fibroin concentration on vascular remodeling in rat model. J Mater Sci: Mater Med 28, 191 (2017). https://doi.org/10.1007/s10856-017-5999-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10856-017-5999-z

Search

Navigation