Study on the Materials Formed by Self-Assembling Hydrophobic, Aromatic Peptides Dedicated to Be Used for Regenerative Medicine Agata Chaberska, a Justyna Fraczyk, a Joanna Wasko, a Piotr Rosiak, a Zbigniew J. Kaminski, a Agnieszka Solecka, b Ewa Stodolak-Zych, b Weronika Strzempek, c Elzbieta Menaszek, c Mariusz Dudek, d Wiktor Niemiec, e and Beata Kolesinska* a a Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland, e-mail: beata.kolesinska@p.lodz.pl b AGH – University of Science and Technology, Department of Biomaterials, A. Mickiewicz 30, 30-059 Krakow, Poland c Department of Cytology, CMUJ, Jagiellonian University Medical College, Swietej Anny 12, 31-008 Krakow, Poland d Institute of Materials Science and Engineering, Lodz University of Technology, Stefanowskiego 1/15, 90-924 Lodz, Poland e AGH – University of Science and Technology, Department of Silicate Chemistry and Macromolecular Com- pounds Department of Silicates Chemistry, A. Mickiewicza 30, 30-059 Krakow, Poland The aims of this study were to identify the short aromatic peptides which are able to form highly ordered amyloid-like structures in self-assembling processes, to test the influence of length of hydrophobic peptides on tendency to aggregation, and to check if aggregated peptides fulfill requirements expected for materials useful for scaffolding. All tested hydrophobic peptides were prepared on solid phase by using DMT/NMM/TsO  as a coupling reagent. The progress of aggregation was studied by set of independent tests. All aggregated peptides were found stable under in vitro conditions. All fibrous material formed by self-assembling of peptides does not show any cytotoxic effects on L929 fibroblast cells. Peptides containing tyrosine and tryptophan residues even effectively accelerated the proliferation and stimulated the activity of L929 fibroblasts. Keywords: aggregation, self-assembling, amyloid-like structure, nanofibril, triazine coupling reagent, hydro- phobic interaction, π – π interaction. Introduction Nanomaterials formed via self-assembling of pep- tides [1] play an increasingly important role in medicine, connecting attributes of nanomaterials with properties typical for biomolecules, which results from bio- degradability, biocompatibility and biomimicry of proteins. These nanomaterials can be widely applied in many fields such as drug delivery, [2,3] nanobiotechnology, [4] regenerative medicine, [5,6] etc. The main factors relevant for triggering process of peptides self-assembling are hydrophobic interactions. Structures formed in this process are stabilized by electrostatic interactions, Van der Waals interactions, π – π interactions and hydrogen bonds. The combined results of all the weak forces engaged in self- assembling dramatically modify the physicochemical properties of parent molecules creating brand new materials, often of unknown and unexpected charac- teristics. Several nanomaterials formed by self-as- sembled peptides are promising scaffolds for tissue engineering. [7] Amphiphilic peptides [8–10] containing repeated units of positively and negatively charged domains separated by neutral, hydrophobic fragments has been found useful for regenerative medicine. The presence of alternative hydrophilic and hydrophobic fragments strongly promotes the process of self- assembling leading to highly ordered supramolecules. DOI: 10.1002/cbdv.201800543 FULL PAPER Chem. Biodiversity 2019, 16, e1800543 © 2019 Wiley-VHCA AG, Zurich, Switzerland