Advertisement

Ultrafine fibrous gelatin scaffolds with deep cell infiltration mimicking 3D ECMs for soft tissue repair

  • Qiuran Jiang
  • Helan Xu
  • Shaobo Cai
  • Yiqi YangEmail author
Article

Abstract

In this research, ultrafine fibrous scaffolds with deep cell infiltration and sufficient water stability have been developed from gelatin, aiming to mimic the extracellular matrices (ECMs) as three dimensional (3D) stromas for soft tissue repair. The ultrafine fibrous scaffolds produced from the current technologies of electrospinning and phase separation are either lack of 3D oriented fibrous structure or too compact to be penetrated by cells. Whilst electrospun scaffolds are able to emulate two dimensional (2D) ECMs, they cannot mimic the 3D ECM stroma. In this work, ultralow concentration phase separation (ULCPS) has been developed to fabricate gelatin scaffolds with 3D randomly oriented ultrafine fibers and loose structures. Besides, a non-toxic citric acid crosslinking system has been established for the ULCPS method. This system could endow the scaffolds with sufficient water stability, while maintain the fibrous structures of scaffolds. Comparing with electrospun scaffolds, the ULCPS scaffolds showed improved cytocompatibility and more importantly, cell infiltration. This research has proved the possibility of using gelatin ULCPS scaffolds as the substitutes of 3D ECMs.

Keywords

Citric Acid Gelatin Gelatin Solution Gelatin Film Citric Acid Concentration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This research was financially supported by Agricultural Research Division at the University of Nebraska-Lincoln, USDA Hatch Act, Multistate Research Project S-1054 (NEB 37-037) and AATCC student research grant. The authors thank the Agricultural Research Division Advisory Committee and the Director of IAPC at the University of Nebraska-Lincoln for the John and Louise Skala Fellowship to Qiuran Jiang and Helan Xu. The authors would also like to acknowledge Prof. Angela Pannier and Prof. Blair D.Siegfried for providing cells and equipment for this research.

References

  1. 1..
    Dvir T, Timko BP, Kohane DS, Langer R. Nanotechnological strategies for engineering complex tissues. Nat Nanotechnol. 2011;6(1):13–22.CrossRefGoogle Scholar
  2. 2.
    Sun T, Norton D, McKean RJ, Haycock JW, Ryan AJ, MacNeil S. Development of a 3D cell culture system for investigating cell interactions with electrospun fibers. Biotechnol Bioeng. 2007;97(5):1318–28.CrossRefGoogle Scholar
  3. 3.
    Gavenis K, Schmidt-Rohlfing B, Mueller-Rath R, Andereya S, Schneider U. In vitro comparison of six different matrix systems for the cultivation of human chondrocytes. In Vitro Cell Dev Biol Anim. 2006;42(5–6):159–67.CrossRefGoogle Scholar
  4. 4.
    Annabi N, Mithieux SM, Weiss AS, Dehghani F. The fabrication of elastin-based hydrogels using high pressure CO2. Biomaterials. 2009;30(1):1–7.CrossRefGoogle Scholar
  5. 5.
    Wang HJ, Fu JX, Wang JY. Effect of water vapor on the surface characteristics and cell compatibility of zein films. Colloid Surf B. 2009;69(1):109–15.CrossRefGoogle Scholar
  6. 6.
    Papenburg BJ, Bolhuis-Versteeg LAM, Grijpma DW, Feijen J, Wessling M, Stamatialis D. A facile method to fabricate poly (l-lactide) nano-fibrous morphologies by phase inversion. Acta Biomater. 2010;6(7):2477–83.CrossRefGoogle Scholar
  7. 7.
    Wei GB, Ma PX. Nanostructured Biomaterials for Regeneration. Adv Funct Mater. 2008;18(22):3568–82.CrossRefGoogle Scholar
  8. 8.
    Kim GM, Le KHT, Giannitelli SM, Lee YJ, Rainer A, Trombetta M. Electrospinning of PCL/PVP blends for tissue engineering scaffolds. J Mater Sci Mater Med. 2013;24(6):1425–42.CrossRefGoogle Scholar
  9. 9.
    Fischer RL, McCoy MG, Grant SA. Electrospinning collagen and hyaluronic acid nanofiber meshes. J Mater Sci Mater Med. 2012;23(7):1645–54.CrossRefGoogle Scholar
  10. 10.
    Tamayol A, Akbari M, Annabi N, Paul A, Khademhosseini A, Juncker D. Fiber-based tissue engineering: progress, challenges, and opportunities. Biotechnol Adv. 2013;31(5):669–87.CrossRefGoogle Scholar
  11. 11.
    Bosworth LA, Alam N, Wong JK, Downes S. Investigation of 2D and 3D electrospun scaffolds intended for tendon repair. J Mater Sci Mater Med. 2013;24(6):1605–14.CrossRefGoogle Scholar
  12. 12.
    Yokoyama Y, Hattori S, Yoshikawa C, Yasuda Y, Koyama H, Takato T, et al. Novel wet electrospinning system for fabrication of spongiform nanofiber 3-dimensional fabric. Mater Lett. 2009;63(9–10):754–6.CrossRefGoogle Scholar
  13. 13.
    Moroni L, Schotel R, Hamann D, de Wijn JR, van Blitterswijk CA. 3D fiber-deposited electrospun integrated scaffolds enhance cartilage tissue formation. Adv Funct Mater. 2008;18(1):53–60.CrossRefGoogle Scholar
  14. 14.
    Simonet M, Schneider OD, Neuenschwander P, Stark WJ. Ultraporous 3D polymer meshes by low-temperature electrospinning: use of ice crystals as a removable void template. Polym Eng Sci. 2007;47(12):2020–6.CrossRefGoogle Scholar
  15. 15.
    Cai S, Xu H, Jiang Q, Yang Y. Novel 3D electrospun scaffolds with fibers oriented randomly and evenly in three dimensions to closely mimic the unique architectures of extracellular matrices in soft tissues: fabrication and mechanism study. Langmuir ACS J Surf Colloids. 2013;29(7):2311–8.CrossRefGoogle Scholar
  16. 16.
    Brown JL, Peach MS, Nair LS, Kumbar SG, Laurencin CT. Composite scaffolds: bridging nanofiber and microsphere architectures to improve bioactivity of mechanically competent constructs. J Biomed Mater Res A. 2010;95(4):1150–8.CrossRefGoogle Scholar
  17. 17.
    Liu XH, Ma PX. Phase separation, pore structure, and properties of nanofibrous gelatin scaffolds. Biomaterials. 2009;30(25):4094–103.CrossRefGoogle Scholar
  18. 18.
    Wang J, Liu XH, Jin XB, Ma HY, Hu JA, Ni LX, et al. The odontogenic differentiation of human dental pulp stem cells on nanofibrous poly(l-lactic acid) scaffolds in vitro and in vivo. Acta Biomater. 2010;6(10):3856–63.CrossRefGoogle Scholar
  19. 19.
    Nam YS, Park TG. Porous biodegradable polymeric scaffolds prepared by thermally induced phase separation. J Biomed Mater Res. 1999;47(1):8–17.CrossRefGoogle Scholar
  20. 20.
    Liu XH, Smith L, Wei GB, Won YJ, Ma PX. Surface engineering of nano-fibrous poly(l-lactic acid) scaffolds via self-assembly technique for bone tissue engineering. J Biomed Nanotechnol. 2005;1(1):54–60.CrossRefGoogle Scholar
  21. 21.
    Liu X, Smith LA, Hu J, Ma PX. Biomimetic nanofibrous gelatin/apatite composite scaffolds for bone tissue engineering. Biomaterials. 2009;30(12):2252–8.CrossRefGoogle Scholar
  22. 22.
    Guan J, Fujimoto KL, Sacks MS, Wagner WR. Preparation and characterization of highly porous, biodegradable polyurethane scaffolds for soft tissue applications. Biomaterials. 2005;26(18):3961–71.CrossRefGoogle Scholar
  23. 23.
    Cen L, Liu W, Cui L, Zhang WJ, Cao YL. Collagen tissue engineering: development of novel biomaterials and applications. Pediatr Res. 2008;63(5):492–6.CrossRefGoogle Scholar
  24. 24.
    Barnes CP, Pemble CW, Brand DD, Simpson DG, Bowlin GL. Cross-linking electrospun type II collagen tissue engineering scaffolds with carbodiimide in ethanol. Tissue Eng. 2007;13(7):1593–605.CrossRefGoogle Scholar
  25. 25.
    Sisson K, Zhang C, Farach-Carson MC, Chase DB, Rabolt JF. Evaluation of cross-linking methods for electrospun gelatin on cell growth and viability. Biomacromolecules. 2009;10(7):1675–80.CrossRefGoogle Scholar
  26. 26.
    Saito Y, Nishio K, Yoshida Y, Niki E. Cytotoxic effect of formaldehyde with free radicals via increment of cellular reactive oxygen species. Toxicology. 2005;210(2–3):235–45.CrossRefGoogle Scholar
  27. 27.
    Verma V, Verma P, Kar S, Ray P, Ray AR. Fabrication of agar–gelatin hybrid scaffolds using a novel entrapment method for in vitro tissue engineering applications. Biotechnol Bioeng. 2007;96(2):392–400.CrossRefGoogle Scholar
  28. 28.
    Jiang Q, Reddy N, Zhang S, Roscioli N, Yang Y. Water-stable electrospun collagen fibers from a nontoxic solvent and crosslinking system. J Biomed Mater Res A. 2012;101:1237–47.Google Scholar
  29. 29.
    Yao C, Li XS, Song TY. Electrospinning and crosslinking of zein nanofiber mats. J Appl Polym Sci. 2007;103:380–5.CrossRefGoogle Scholar
  30. 30.
    Jiang QR, Reddy N, Yang YQ. Cytocompatible cross-linking of electrospun zein fibers for the development of water-stable tissue engineering scaffolds. Acta Biomater. 2010;6(10):4042–51.CrossRefGoogle Scholar
  31. 31.
    Gu SY, Wang ZM, Ren J, Zhang CY. Electrospinning of gelatin and gelatin/poly (l-lactide) blend and its characteristics for wound dressing. Mat Sci Eng C Mater. 2009;29(6):1822–8.CrossRefGoogle Scholar
  32. 32.
    Jiang QR, Yang YQ. Water-stable electrospun zein fibers for potential drug delivery. J Biomater Sci Polym Ed. 2011;22(10):1393–408.CrossRefGoogle Scholar
  33. 33.
    Hynes RO, Naba A. Overview of the matrisome—an inventory of extracellular matrix constituents and functions. Cold Spring Harb Perspect Biol. 2012;4(1):a004903.CrossRefGoogle Scholar
  34. 34.
    Clark RK. Construction materials of your body: the tissue. In: Clark RK, editor. Anatomy and physiology: understanding the human body. America: Jones and Bartlett Publishers, Inc.; 2004. p. 65.Google Scholar
  35. 35.
    Hua FJ, Kim GE, Lee JD, Son YK, Lee DS. Macroporous poly(l-lactide) scaffold 1. Preparation of a macroporous scaffold by liquid–liquid phase separation of a PLLA–dioxane–water system. J Biomed Mater Res. 2002;63(2):161–7.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Qiuran Jiang
    • 1
  • Helan Xu
    • 1
  • Shaobo Cai
    • 1
  • Yiqi Yang
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of Textiles, Merchandising and Fashion DesignUniversity of Nebraska-LincolnLincolnUSA
  2. 2.Department of Biological Systems EngineeringUniversity of Nebraska-LincolnLincolnUSA
  3. 3.Nebraska Center for Materials and NanoscienceUniversity of Nebraska-LincolnLincolnUSA

Personalised recommendations