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Cross-linked self-assembling peptide scaffolds

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Abstract

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.

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Acknowledgements

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.

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Authors and Affiliations

  1. IRCCS Casa Sollievo della Sofferenza, Opera di San Pio da Pietralcina, Viale Capuccini 1 San Giovanni Rotondo, Foggia, 71013, Italy

    Raffaele Pugliese, Amanda Marchini & Fabrizio Gelain

  2. Center for Nanomedicine and Tissue Engineering (CNTE), A. O. Ospedale Niguarda Cà Granda, Piazza dell’ Ospedale Maggiore 3, Milan, 20162, Italy

    Amanda Marchini, Gloria Anna Ada Saracino & Fabrizio Gelain

  3. The Molecular Foundry, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, California, 94720, USA

    Ronald N. Zuckermann

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  1. Raffaele Pugliese
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  2. Amanda Marchini
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  3. Gloria Anna Ada Saracino
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  4. Ronald N. Zuckermann
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  5. Fabrizio Gelain
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Correspondence to Fabrizio Gelain.

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Pugliese, R., Marchini, A., Saracino, G.A.A. et al. Cross-linked self-assembling peptide scaffolds. Nano Res. 11, 586–602 (2018). https://doi.org/10.1007/s12274-017-1834-6

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