Skip to main content
SpringerLink
Log in

Bio-fabrication and physiological self-release of tissue equivalents using smart peptide amphiphile templates

  • Special Issue: ESB 2015
  • Tissue engineering constructs and cell substrates
  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

In this study we applied a smart biomaterial formed from a self-assembling, multi-functional synthetic peptide amphiphile (PA) to coat substrates with various surface chemistries. The combination of PA coating and alignment-inducing functionalised substrates provided a template to instruct human corneal stromal fibroblasts to adhere, become aligned and then bio-fabricate a highly-ordered, multi-layered, three-dimensional tissue by depositing an aligned, native-like extracellular matrix. The newly-formed corneal tissue equivalent was subsequently able to eliminate the adhesive properties of the template and govern its own complete release via the action of endogenous proteases. Tissues recovered through this method were structurally stable, easily handled, and carrier-free. Furthermore, topographical and mechanical analysis by atomic force microscopy showed that tissue equivalents formed on the alignment-inducing PA template had highly-ordered, compact collagen deposition, with a two-fold higher elastic modulus compared to the less compact tissues produced on the non-alignment template, the PA-coated glass. We suggest that this technology represents a new paradigm in tissue engineering and regenerative medicine, whereby all processes for the bio-fabrication and subsequent self-release of natural, bio-prosthetic human tissues depend solely on simple template-tissue feedback interactions.

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

Similar content being viewed by others

References

  1. Rice JJ, Martino MM, De Laporte L, Tortelli F, Briquez PS, Hubbell JA. Engineering the regenerative microenvironment with biomaterials. Advanced Healthc Mater. 2013;2:57–71.

    Article  Google Scholar 

  2. Jones RR, Hamley IW, Connon CJ. Chapter 4 the instructive role of biomaterials in cell-based therapy and tissue engineering. Hydrogels in cell-based therapies. Cambridge: The Royal Society of Chemistry; 2014. p. 73–94.

    Google Scholar 

  3. Liu JS, Gartner ZJ. Directing the assembly of spatially organized multicomponent tissues from the bottom up. Trends Cell Biol. 2012;22:683–91.

    Article  Google Scholar 

  4. Samchenko Y, Ulberg Z, Korotych O. Multipurpose smart hydrogel systems. Adv Colloid Interface Sci. 2011;168:247–62.

    Article  Google Scholar 

  5. Hayashida Y, Nishida K, Yamato M, Yang J, Sugiyama H, Watanabe K, et al. Transplantation of tissue-engineered epithelial cell sheets after excimer laser photoablation reduces postoperative corneal haze. Invest Ophthalmol Vis Sci. 2006;47:552–7.

    Article  Google Scholar 

  6. Dworak A, Utrata-Wesolek A, Oleszko N, Walach W, Trzebicka B, Aniol J, et al. Poly(2-substituted-2-oxazoline) surfaces for dermal fibroblasts adhesion and detachment. J Mater Sci Mater Med. 2014;25:1149–63.

    Article  Google Scholar 

  7. Takagi R, Murakami D, Kondo M, Ohki T, Sasaki R, Mizutani M, et al. Fabrication of human oral mucosal epithelial cell sheets for treatment of esophageal ulceration by endoscopic submucosal dissection. Gastrointest Endosc. 2010;72:1253–9.

    Article  Google Scholar 

  8. Hama T, Yamamoto K, Yaguchi Y, Murakami D, Sasaki H, Yamato M, et al. Autologous human nasal epithelial cell sheet using temperature-responsive culture insert for transplantation after middle ear surgery. J Tissue Eng Regen Med. 2015. doi:10.1002/term.2012.

  9. Sakaguchi K, Shimizu T, Okano T. Construction of three-dimensional vascularized cardiac tissue with cell sheet engineering. J Control Release. 2015;205:83–8.

    Article  Google Scholar 

  10. Aranaz I, Martinez-Campos E, Nash ME, Tardajos MG, Reinecke H, Elvira C, et al. Pseudo-double network hydrogels with unique properties as supports for cell manipulation. J Mater Chem B. 2014;2:3839–48.

    Article  Google Scholar 

  11. Hruschka V, Saeed A, Slezak P, Cheikh Al Ghanami R, Feichtinger GA, Alexander C, et al. Evaluation of a thermoresponsive polycaprolactone scaffold for in vitro three-dimensional stem cell differentiation. Tissue Eng Part A. 2015;21:310–9.

    Article  Google Scholar 

  12. Sekiya S, Shimizu T, Okano T. Vascularization in 3D tissue using cell sheet technology. Regen Med. 2013;8:371–7.

    Article  Google Scholar 

  13. Matsuura K, Utoh R, Nagase K, Okano T. Cell sheet approach for tissue engineering and regenerative medicine. J Control Release. 2014;190:228–39.

    Article  Google Scholar 

  14. Boekhoven J, Stupp SI. 25th Anniversary article: supramolecular materials for regenerative medicine. Adv Mater. 2014;26:1642–59.

    Article  Google Scholar 

  15. Hamley IW. Lipopeptides: from self-assembly to bioactivity. Chem Commun. 2015;51:8574–83.

    Article  Google Scholar 

  16. Dehsorkhi A, Gouveia RM, Smith AM, Hamley IW, Castelletto V, Connon CJ, et al. Self-assembly of a dual functional bioactive peptide amphiphile incorporating both matrix metalloprotease substrate and cell adhesion motifs. Soft Matter. 2015;11:3115–24.

    Article  Google Scholar 

  17. Gouveia RM, Castelletto V, Hamley IW, Connon CJ. New self-assembling multifunctional templates for the biofabrication and controlled self-release of cultured tissue. Tissue Eng Part A. 2015;21:1772–84.

    Article  Google Scholar 

  18. Miotto M, Gouveia RM, Connon CJ. Peptide amphiphiles in corneal tissue engineering. J Funct Biomater. 2015;6:687–707.

    Article  Google Scholar 

  19. Lewis PN, Pinali C, Young RD, Meek KM, Quantock AJ, Knupp C. Structural interactions between collagen and proteoglycans are elucidated by three-dimensional electron tomography of bovine cornea. Structure. 2010;18:239–45.

    Article  Google Scholar 

  20. Gouveia RM, Castelletto V, Alcock SG, Hamley IW, Connon CJ. Bioactive films produced from self-assembling peptide amphiphiles as versatile substrates for tuning cell adhesion and tissue architecture in serum-free conditions. J Mater Chem B. 2013;1:6157–69.

    Article  Google Scholar 

  21. Gouveia RM, Connon CJ. The effects of retinoic acid on human corneal stromal keratocytes cultured in vitro under serum-free conditions. Invest Ophthalmol Vis Sci. 2013;54:7483–91.

    Article  Google Scholar 

  22. Wittmann JC, Smith P. Highly oriented thin-films of poly(tetrafluoroethylene) as a substrate for oriented growth of materials. Nature. 1991;352:414–7.

    Article  Google Scholar 

  23. Lin DC, Horkay F. Nanomechanics of polymer gels and biological tissues: a critical review of analytical approaches in the Hertzian regime and beyond. Soft Matter. 2008;4:669–82.

    Article  Google Scholar 

  24. Holmes DF, Gilpin CJ, Baldock C, Ziese U, Koster AJ, Kadler KE. Corneal collagen fibril structure in three dimensions: structural insights into fibril assembly, mechanical properties, and tissue organization. Proc Natl Acad Sci USA. 2001;98:7307–12.

    Article  Google Scholar 

  25. Komai Y, Ushiki T. The three-dimensional organization of collagen fibrils in the human cornea and sclera. Invest Ophthalmol Vis Sci. 1991;32:2244–58.

    Google Scholar 

  26. Chen B, Jones RR, Mi SL, Foster J, Alcock SG, Hamley IW, et al. The mechanical properties of amniotic membrane influence its effect as a biomaterial for ocular surface repair. Soft Matter. 2012;8:8379–87.

    Article  Google Scholar 

  27. Hamley IW, Castelletto V, Moulton CM, Rodriguez-Perez J, Squires AM, Eralp T, et al. Alignment of a model amyloid peptide fragment in bulk and at a solid surface. J Phys Chem B. 2010;114:8244–54.

    Article  Google Scholar 

  28. Foster JW, Jones RR, Bippes CA, Gouveia RM, Connon CJ. Differential nuclear expression of Yap in basal epithelial cells across the cornea and substrates of differing stiffness. Exp Eye Res. 2014;127:37–41.

    Article  Google Scholar 

  29. Loparic M, Wirz D, Daniels AU, Raiteri R, Vanlandingham MR, Guex G, et al. Micro- and nanomechanical analysis of articular cartilage by indentation-type atomic force microscopy: validation with a gel-microfiber composite. Biophys J. 2010;98:2731–40.

    Article  Google Scholar 

  30. Stolz M, Raiteri R, Daniels AU, VanLandingham MR, Baschong W, Aebi U. Dynamic elastic modulus of porcine articular cartilage determined at two different levels of tissue organization by indentation-type atomic force microscopy. Biophys J. 2004;86:3269–83.

    Article  Google Scholar 

  31. Achterberg VF, Buscemi L, Diekmann H, Smith-Clerc J, Schwengler H, Meister JJ, et al. The nano-scale mechanical properties of the extracellular matrix regulate dermal fibroblast function. J Invest Dermatol. 2014;134:1862–72.

    Article  Google Scholar 

  32. Crichton ML, Donose BC, Chen X, Raphael AP, Huang H, Kendall MA. The viscoelastic, hyperelastic and scale dependent behaviour of freshly excised individual skin layers. Biomaterials. 2011;32:4670–81.

    Article  Google Scholar 

  33. Lombardo M, Lombardo G, Carbone G, De Santo MP, Barberi R, Serrao S. Biomechanics of the anterior human corneal tissue investigated with atomic force microscopy. Invest Ophthalmol Vis Sci. 2012;53:1050–7.

    Article  Google Scholar 

  34. Shen ZL, Kahn H, Ballarini R, Eppell SJ. Viscoelastic properties of isolated collagen fibrils. Biophys J. 2011;100:3008–15.

    Article  Google Scholar 

Download references

Acknowledgments

We thank Dr C. A. Bipes from Nanosurf AG, Switzerland for his expert technical support in atomic force microscopy. This work was funded by the Biotechnology and Biological Sciences Research Council (BBSRC Grant Reference BB/I008187/1).

Author information

Authors and Affiliations

  1. Institute of Genetic Medicine, International Centre for Life, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK

    Ricardo M. Gouveia & Che J. Connon

  2. Department of Chemistry, University of Reading, Whiteknights, Reading, RG6 6AD, UK

    Ian W. Hamley

Authors
  1. Ricardo M. Gouveia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ian W. Hamley
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Che J. Connon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Che J. Connon.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gouveia, R.M., Hamley, I.W. & Connon, C.J. Bio-fabrication and physiological self-release of tissue equivalents using smart peptide amphiphile templates. J Mater Sci: Mater Med 26, 242 (2015). https://doi.org/10.1007/s10856-015-5581-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10856-015-5581-5

Keywords

Search

Navigation