Skip to main content
Log in

Electrospun silk fibroin–gelatin composite tubular matrices as scaffolds for small diameter blood vessel regeneration

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

Abstract

In this work an innovative method to obtain natural and biocompatible small diameter tubular structures is proposed. The biocompatibility and good mechanical properties of electrospun silk fibroin tubular matrices (SFts), extensively studied for tissue engineering applications, have been coupled with the excellent cell interaction properties of gelatin. In fact, an innovative non-cytotoxic gelatin gel, crosslinked in mild conditions via a Michael-type addition reaction, has been used to coat SFt matrices and obtain SFt/gel structures (I.D. = 6 mm). SFts/gel exhibited homogeneous gelatin coating on the electrospun fibrous tubular structure. Circumferential tensile tests performed on SFts/gel showed mechanical properties comparable to those of natural blood vessels in terms of UTS, compliance and viscoelastic behavior. Finally, SFt/gel in vitro cytocompatibility was confirmed by the good viability and spread morphology of L929 fibroblasts up to 7 days. These results demonstrated that SFt/gel is a promising off-the-shelf graft for small diameter blood vessel regeneration.

Graphical Abstract

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Catto V, Fare S, Cattaneo I, Figliuzzi M, Alessandrino A, Freddi G, Remuzzi A, Tanzi MC. Small diameter electrospun silk fibroin vascular grafts: mechanical properties, in vitro biodegradability, and in vivo biocompatibility. Mater Sci Eng C. 2015;54:101–11.

    Article  Google Scholar 

  2. Marelli B, Alessandrino A, Fare S, Freddi G, Mantovani D, Tanzi MC. Compliant electrospun silk fibroin tubes for small vessel bypass grafting. Acta Biomater. 2010;6:4019–26.

    Article  Google Scholar 

  3. Rathore A, Cleary M, Naito Y, Rocco K, Breuer C. Development of tissue engineered vascular grafts and application of nanomedicine. Wires Nanomed Nanobiotechnol. 2012;4:257–72.

    Article  Google Scholar 

  4. Catto V, Fare S, Freddi G, Tanzi MC. Vascular tissue engineering: recent advances in small diameter blood vessel regeneration. ISRN Vasc Med. 2014;2014:27

    Google Scholar 

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

    Article  Google Scholar 

  6. Lovett M, Eng G, Kluge JA, Cannizzaro C, Vunjak-Novakovic G, Kaplan DL. Tubular silk scaffolds for small diameter vascular grafts. Organogenesis. 2010;6:217–24.

    Article  Google Scholar 

  7. Wang SD, Zhang YZ, Wang HW, Yin GB, Dong ZH. Fabrication and properties of the electrospun polylactide/silk fibroin-gelatin composite tubular scaffold. Biomacromolecules. 2009;10:2240–44.

    Article  Google Scholar 

  8. Pankajakshan D, Agrawal DK. Scaffolds in tissue engineering of blood vessels. Can J Physiol Pharm. 2010;88:855–73.

    Article  Google Scholar 

  9. Marelli B, Achilli M, Alessandrino A, Freddi G, Tanzi MC, Fare S, Mantovani D. Collagen-reinforced electrospun silk fibroin tubular construct as small calibre vascular graft. Macromol Biosci. 2012;12:1566–74.

    Article  Google Scholar 

  10. Cattaneo I, Figliuzzi M, Azzollini N, Catto V, Fare S, Tanzi MC, Alessandrino A, Freddi G, Remuzzi A. In vivo regeneration of elastic lamina on fibroin biodegradable vascular scaffold. Int J Artif Organs. 2013;36:166–74.

    Article  Google Scholar 

  11. Lee KY, Mooney DJ. Hydrogels for tissue engineering. Chem Rev. 2001;101:1869–79.

    Article  Google Scholar 

  12. Hoch E, Schuh C, Hirth T, Tovar GEM, Borchers K. Stiff gelatin hydrogels can be photo-chemically synthesized from low viscous gelatin solutions using molecularly functionalized gelatin with a high degree of methacrylation. J Mater Sci. 2012;23:2607–17.

    Google Scholar 

  13. Young S, Wong M, Tabata Y, Mikos AG. Gelatin as a delivery vehicle for the controlled release of bioactive molecules. J Control Release. 2005;109:256–74.

    Article  Google Scholar 

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

    Article  Google Scholar 

  15. Wray LS, Hu X, Gallego J, Georgakoudi I, Omenetto FG, Schmidt D, Kaplan DL. Effect of processing on silk-based biomaterials: reproducibility and biocompatibility. J Biomed Mater Res B. 2011;99B:89–101.

    Article  Google Scholar 

  16. Rockwood DN, Preda RC, Yucel T, Wang XQ, Lovett ML, Kaplan DL. Materials fabrication from Bombyx mori silk fibroin. Nat Protoc. 2011;6:1612–31.

    Article  Google Scholar 

  17. Motta A, Migliaresi C, Faccioni F, Torricelli P, Fini M, Giardino R. Fibroin hydrogels for biomedical applications: preparation, characterization and in vitro cell culture studies. J Biomater Sci Polym Ed. 2004;15:851–64.

    Article  Google Scholar 

  18. Sugihara A, Sugiura K, Morita H, Ninagawa T, Tubouchi K, Tobe R, Izumiya M, Horio T, Abraham NG, Ikehara S. Promotive effects of a silk film on epidermal recovery from full-thickness skin wounds. Proc Soc Exp Biol Med. 2000;225:58–64.

    Article  Google Scholar 

  19. Meinel L, Hofmann S, Karageorgiou V, Zichner L, Langer R, Kaplan D, Vunjak-Novakovic G. Engineering cartilage-like tissue using human mesenchymal stem cells and silk protein scaffolds. Biotechnol Bioeng. 2004;88:379–91.

    Article  Google Scholar 

  20. Yeo JH, Lee KG, Kim HC, Oh YL, Kim AJ, Kim SY. The effects of PVA/Chitosan/Fibroin (PCF)-blended spongy sheets on wound healing in rats. Biol Pharm Bull. 2000;23:1220–23.

    Article  Google Scholar 

  21. Fischer RL, McCoy MG, Grant SA. Electrospinning collagen and hyaluronic acid nanofiber meshes. J Mater Sci. 2012;23:1645–54.

    Google Scholar 

  22. Soffer L, Wang XY, Zhang XH, Kluge J, Dorfmann L, Kaplan DL, Leisk G. Silk-based electrospun tubular scaffolds for tissue-engineered vascular grafts. J Biomater Sci Polym Ed. 2008;19:653–664.

    Article  Google Scholar 

  23. Salacinski HJ, Goldner S, Giudiceandrea A, Hamilton G, Seifalian AM, Edwards A, Carson RJ. The mechanical behavior of vascular grafts: a review. J Biomater Appl. 2001;15:241–78.

    Article  Google Scholar 

  24. Kannan RY, Salacinski HJ, Butler PE, Hamilton G, Seifalian AM. Current status of prosthetic bypass grafts: a review. J Biomed Mater Res B. 2005;74B:570–81.

    Article  Google Scholar 

  25. Mizelle S. W., Gupta B. S., Kasyanov V. A. (1995) Compliance of small-diameter vascular grafts as a determinant of patency. Proceedings of the 1995 Fourteenth Southern Biomedical Engineering Conference 1995. 7–9 April 1995, pp. 30–33.

  26. Konig G, McAllister TN, Dusserre N, Garrido SA, Iyican C, Marini A, Fiorillo A, Avila H, Wystrychowski W, Zagalski K, Maruszewski M, Jones AL, Cierpka L, de la Fuente LM, L’Heureux N. Mechanical properties of completely autologous human tissue engineered blood vessels compared to human saphenous vein and mammary artery. Biomaterials. 2009;30:1542–50.

    Article  Google Scholar 

  27. Enomoto S, Sumi M, Kajimoto K, Nakazawa Y, Takahashi R, Takabayashi C, Asakura T, Sata M. Long-term patency of small-diameter vascular graft made from fibroin, a silk-based biodegradable material. J Vasc Surg. 2010;51:155–64.

    Article  Google Scholar 

  28. Siess W. Molecular mechanism of platelet activation. Fortschr Med. 1985;103:937

    Google Scholar 

  29. Madaghiele M, Piccinno A, Saponaro M, Maffezzoli A, Sannino A. Collagen- and gelatine-based films sealing vascular prostheses: evaluation of the degree of crosslinking for optimal blood impermeability. J Mater Sci. 2009;20:1979–89.

    Google Scholar 

  30. Kretlow JD, Klouda L, Mikos AG. Injectable matrices and scaffolds for drug delivery in tissue engineering. Adv Drug Deliv Rev. 2007;59:263–73.

    Article  Google Scholar 

  31. Kuijpers AJ, Engbers GHM, Krijgsveld J, Zaat SAJ, Dankert J, Feijen J. Cross-linking and characterisation of gelatin matrices for biomedical applications. J Biomater Sci Polym Ed. 2000;11:225–43.

    Article  Google Scholar 

  32. Wang SD, Zhang YZ, Yin GB, Wang HW, Dong ZH. Fabrication of a composite vascular scaffold using electrospinning technology. Mater Sci Eng C. 2010;30:670–76.

    Article  Google Scholar 

  33. Okhawilai M, Rangkupan R, Kanokpanont S, Damrongsakkul S. Preparation of Thai silk fibroin/gelatin electrospun fiber mats for controlled release applications. Int J Biol Macromol. 2010;46:544–50.

    Article  Google Scholar 

  34. Somvipart S, Kanokpanont S, Rangkupan R, Ratanavaraporn J, Damrongsakkul S. Development of electrospun beaded fibers from Thai silk fibroin and gelatin for controlled release application. Int J Biol Macromol. 2013;55:176–84.

    Article  Google Scholar 

  35. Gui-bo Y, You-zhu Z, Wei-wei B, Jialin W, De-bing S, Zhi-hui D, Wei-guo F. Study on the properties of the electrospun silk fibroin/gelatin blend nanofibers for scaffolds. J Appl Polym Sci. 2009;111:1471–77.

    Article  Google Scholar 

  36. Tanzi MC, Fare’ S, Gerges I. Crosslinked gelatin hydrogels. PCT/EP2012/060277. 2012

  37. Achilli M, Meghezi S, Mantovani D. On the viscoelastic properties of collagen-gel-based lattices under cyclic loading: applications for vascular tissue engineering. Macromol Mater Eng. 2012;297:724–34.

    Article  Google Scholar 

  38. Sato M, Nakazawa Y, Takahashi R, Tanaka K, Sata M, Aytemiz D, Asakura T. Small-diameter vascular grafts of Bombyx mori silk fibroin prepared by a combination of electrospinning and sponge coating. Mater Lett. 2010;64:1786–88.

    Article  Google Scholar 

  39. Chen KY, Dong GC, Hsu CY, Chen YS, Yao CH. Autologous bone marrow stromal cells loaded onto porous gelatin scaffolds containing Drynaria fortunei extract for bone repair. J Biomed Mater Res A. 2013;101:954–62.

    Article  Google Scholar 

  40. Liang HC, Chang WH, Liang HF, Lee MH, Sung HW. Crosslinking structures of gelatin hydrogels crosslinked with genipin or a water-soluble carbodiimide. J Appl Polym Sci. 2004;91:4017–26.

    Article  Google Scholar 

  41. Yao L, Liu JY, Andreadis ST. Composite fibrin scaffolds increase mechanical strength and preserve contractility of tissue engineered blood vessels. Pharm Res. 2008;25:1212–21.

    Article  Google Scholar 

  42. McKenna KA, Hinds MT, Sarao RC, Wu PC, Maslen CL, Glanville RW, Babcock D, Gregory KW. Mechanical property characterization of electrospun recombinant human tropoelastin for vascular graft biomaterials. Acta Biomater. 2012;8:225–33.

    Article  Google Scholar 

  43. Tillman BW, Yazdani SK, Lee SJ, Geary RL, Atala A, Yoo JJ. The in vivo stability of electrospun polycaprolactone-collagen scaffolds in vascular reconstruction. Biomaterials. 2009;30:583–588.

    Article  Google Scholar 

  44. Wu W, Allen RA, Wang YD. Fast-degrading elastomer enables rapid remodeling of a cell-free synthetic graft into a neoartery. Nat Med. 2012;18:1148

    Article  Google Scholar 

  45. He W, Ma ZW, Teo WE, Dong YX, Robless PA, Lim TC, Ramakrishna S. Tubular nanofiber scaffolds for tissue engineered small-diameter vascular grafts. J Biomed Mater Res A. 2009;90A:205–16.

    Article  Google Scholar 

  46. Uchida T, Ikeda S, Oura H, Tada M, Nakano T, Fukuda T, Matsuda T, Negoro M, Arai F. Development of biodegradable scaffolds based on patient-specific arterial configuration. J Biotechnol. 2008;133:213–18.

    Article  Google Scholar 

  47. Wise SG, Byrom MJ, Waterhouse A, Bannon PG, Weiss AS, Ng MKC. A multilayered synthetic human elastin/polycaprolactone hybrid vascular graft with tailored mechanical properties. Acta Biomater. 2011;7:1429

    Article  Google Scholar 

  48. Wang C, Cen L, Yin S, Liu QH, Liu W, Cao YL, Cui L. A small diameter elastic blood vessel wall prepared under pulsatile conditions from polyglycolic acid mesh and smooth muscle cells differentiated from adipose-derived stem cells. Biomaterials. 2010;31:621–30.

    Article  Google Scholar 

  49. de Valence S, Tille JC, Giliberto JP, Mrowczynski W, Gurny R, Walpoth BH, Moller M. Advantages of bilayered vascular grafts for surgical applicability and tissue regeneration. Acta Biomater. 2012;8:3914–20.

    Article  Google Scholar 

  50. de Valence S, Tille JC, Mugnai D, Mrowczynski W, Gurny R, Moller M, Walpoth BH. Long term performance of polycaprolactone vascular grafts in a rat abdominal aorta replacement model. Biomaterials. 2012;33:38–47.

    Article  Google Scholar 

  51. Roh JD, Nelson GN, Brennan MP, Mirensky TL, Yi T, Hazlett TF, Tellides G, Sinusas AJ, Pober JS, Saltzman WM, Kyriakides TR, Breuer CK. Small-diameter biodegradable scaffolds for functional vascular tissue engineering in the mouse model. Biomaterials. 2008;29:1454–63.

    Article  Google Scholar 

  52. McClure MJ, Sell SA, Simpson DG, Walpoth BH, Bowlin GL. A three-layered electrospun matrix to mimic native arterial architecture using polycaprolactone, elastin, and collagen: a preliminary study. Acta Biomater. 2010;6:2422–33.

    Article  Google Scholar 

  53. Lee SJ, Liu J, Oh SH, Soker S, Atala A, Yoo JJ. Development of a composite vascular scaffolding system that withstands physiological vascular conditions. Biomaterials. 2008;29:2891–98.

    Article  Google Scholar 

  54. Berglund JD, Nerem RM, Sambanis A. Viscoelastic testing methodologies for tissue engineered blood vessels. J Biomech Eng. 2005;127:1176–84.

    Article  Google Scholar 

  55. Manju S, Muraleedharan CV, Rajeev A, Jayakrishnan A, Joseph R. Evaluation of alginate dialdehyde cross-linked gelatin hydrogel as a biodegradable sealant for polyester vascular graft. J Biomed Mater Res B. 2011;98B:139–49.

    Article  Google Scholar 

  56. Lu WD, Zhang M, Wu ZS, Hu TH. Decellularized and photooxidatively crosslinked bovine jugular veins as potential tissue engineering scaffolds. Interact Cardiovasc Thorac Surg. 2009;8:301–5.

    Article  Google Scholar 

  57. Assmann A, Delfs C, Munakata H, Schiffer F, Horstkotter K, Huynh K, Barth M, Stoldt VR, Kamiya H, Boeken U, Lichtenberg A, Akhyari P. Acceleration of autologous in vivo recellularization of decellularized aortic conduits by fibronectin surface coating. Biomaterials. 2013;34:6015–26.

    Article  Google Scholar 

  58. Jordan SW, Haller CA, Sallach RE, Apkarian RP, Hanson SR, Chaikof EL. The effect of a recombinant elastin-mimetic coating of an ePTFE prosthesis on acute thrombogenicity in a baboon arteriovenous shunt. Biomaterials. 2007;28:1191–97.

    Article  Google Scholar 

  59. Koch S, Flanagan TC, Sachweh JS, Tanios F, Schnoering H, Deichmann T, Ella V, Kellomaki M, Gronloh N, Gries T, Tolba R, Schmitz-Rode T, Jockenhoevel S. Fibrin-polylactide-based tissue-engineered vascular graft in the arterial circulation. Biomaterials. 2010;31:4731–39.

    Article  Google Scholar 

  60. Deutsch M, Meinhart J, Zilla P, Howanietz N, Gorlitzer M, Froeschl A, Stuempflen A, Bezuidenhout D, Grabenwoeger M. Long-term experience in autologous in vitro endothelialization of infrainguinal ePTFE grafts. J Vasc Surg. 2009;49:352–62.

    Article  Google Scholar 

  61. Woodhouse KA, Klement P, Chen V, Gorbet MB, Keeley FW, Stahl R, Fromstein JD, Bellingham CM. Investigation of recombinant human elastin polypeptides as non-thrombogenic coatings. Biomaterials. 2004;25:4543–53.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Silvia Faré.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Marcolin, C., Draghi, L., Tanzi, M. et al. Electrospun silk fibroin–gelatin composite tubular matrices as scaffolds for small diameter blood vessel regeneration. J Mater Sci: Mater Med 28, 80 (2017). https://doi.org/10.1007/s10856-017-5884-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10856-017-5884-9

Navigation