Nano Research

, Volume 11, Issue 1, pp 586–602 | Cite as

Cross-linked self-assembling peptide scaffolds

  • Raffaele Pugliese
  • Amanda Marchini
  • Gloria Anna Ada Saracino
  • Ronald N. Zuckermann
  • Fabrizio GelainEmail author
Research Article


Self-assembling peptides (SAPs) are synthetic bioinspired biomaterials that can be feasibly multi-functionalized for cell transplantation and/or drug delivery therapies. Despite their superior biocompatibility and ease of scaling-up for production, they are unfortunately hampered by weak mechanical properties due to transient non-covalent interactions among and within the self-assembled peptide chains, thus limiting their potential applications as fillers, hemostat solutions, and fragile scaffolds for soft tissues. Here, we have developed and characterized a cross-linking strategy that increases both the stiffness and the tailorability of SAP hydrogels, enabling the preparation of transparent flexible threads, discs, channels, and hemispherical constructs. Empirical and computational results, in close agreement with each other, confirmed that the cross-linking reaction does not affect the previously self-assembled secondary structures. In vitro tests also provided a first hint of satisfactory biocompatibility by favoring viability and differentiation of human neural stem cells. This work could bring self-assembling peptide technology to many applications that have been precluded so far, especially in regenerative medicine.


self-assembling peptide co-assembling peptide cross-linking sulfo-SMCC supramolecular self-assembly 


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Work described and performed by R. P., G. S., and F. G. was funded by Fondazione Cariplo under Grant no. 2011-0352, by La Colonna Onlus, by the “Ricerca Corrente 2015–2016” funding granted by the Italian Ministry of Health and by the “5 × 1000” voluntary contributions. A. M. is supported by a fellowship granted by Vertical Onlus. Raman, XRD, FTIR and WAXS experiments were conducted at the Advanced Light Source and at the Molecular Foundry, at the Lawrence Berkeley National Laboratory, both of which are supported by the Office of Science, under Contract No. DE-AC02-05CH11231. We thank Alice Nodari for her help in SAP production and QC tests.

Supplementary material

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Cross-linked self-assembling peptide scaffolds.
12274_2017_1834_MOESM2_ESM.mp4 (1.8 mb)
Supplementary material, approximately 1.77 MB.
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Supplementary material, approximately 1.10 MB.


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Copyright information

© Tsinghua University Press and Springer-Verlag GmbH Germany 2018

Authors and Affiliations

  • Raffaele Pugliese
    • 1
  • Amanda Marchini
    • 1
    • 2
  • Gloria Anna Ada Saracino
    • 2
  • Ronald N. Zuckermann
    • 3
  • Fabrizio Gelain
    • 1
    • 2
    Email author
  1. 1.IRCCS Casa Sollievo della SofferenzaOpera di San Pio da PietralcinaFoggiaItaly
  2. 2.Center for Nanomedicine and Tissue Engineering (CNTE)A. O. Ospedale Niguarda Cà GrandaMilanItaly
  3. 3.The Molecular FoundryLawrence Berkeley National LaboratoryBerkeleyUSA

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