title: BMHP1-derived self-assembling peptides: hierarchically assembled structures with self-healing propensity and potential for tissue engineering applications.
abstract: Self-assembling peptides (SAPs) are rapidly gaining interest as bioinspired scaffolds for cell culture and regenerative medicine applications. Bone Marrow Homing Peptide 1 (BMHP1) functional motif (PFSSTKT) was previously demonstrated to stimulate neural stem cell (NSC) viability and differentiation when linked to SAPs. We here describe a novel ensemble of SAPs, developed from the BMHP1 (BMHP1-SAPs), that spontaneously assemble into tabular fibers, twisted ribbons, tubes and hierarchical self-assembled sheets: organized structures in the nano- and microscale. Thirty-two sequences were designed and evaluated, including biotinylated and unbiotinylated sequences, as well as a hybrid peptide-peptoid sequence. Via X-ray diffraction (XRD), CD, and FTIR experiments we demonstrated that all of the BMHP1-SAPs share similarly organized secondary structures, that is, β-sheets and β-turns, despite their heterogeneous nanostructure morphology, scaffold stiffness, and effect over NSC differentiation and survival. Notably, we demonstrated the self-healing propensity of most of the tested BMHP1-SAPs, enlarging the set of potential applications of these novel SAPs. In in vitro cell culture experiments, we showed that some of these 10-mer peptides foster adhesion, differentiation, and proliferation of human NSCs. RGD-functionalized and hybrid peptide-peptoid self-assembling sequences also opened the door to BMHP1-SAP functionalization with further bioactive motifs, essential to tailor new scaffolds for specific applications. In in vivo experiments we verified a negligible reaction of the host nervous tissue to the injected and assembled BMHP1-SAP. This work will pave the way to the development of novel SAP sequences that may be useful for material science and regenerative medicine applications.
authors.affiliation: Center for Nanomedicine and Tissue Engineering-A.O. Ospedale Niguarda Ca' Granda, Piazza dell'ospedale maggiore 3, Milan, 20162, Italy. fabrizio.gelain@unimib.it
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Gelain
authors.forename: Diego
authors.initials: D
authors.lastname: Silva
authors.forename: Andrea
authors.initials: A
authors.lastname: Caprini
authors.forename: Francesca
authors.initials: F
authors.lastname: Taraballi
authors.forename: Antonino
authors.initials: A
authors.lastname: Natalello
authors.forename: Omar
authors.initials: O
authors.lastname: Villa
authors.forename: Ki Tae
authors.initials: KT
authors.lastname: Nam
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Zuckermann
authors.forename: Silvia Maria
authors.initials: SM
authors.lastname: Doglia
authors.forename: Angelo
authors.initials: A
authors.lastname: Vescovi
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005240:Feasibility Studies; D006801:Humans; D009414:Nerve Growth Factors / Q000138:chemical synthesis* / Q000494:pharmacology*; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D009414:Nerve Growth Factors