Self-assembling peptide scaffolds for regenerative medicine

Abstract

Biomaterials made from self-assembling, short peptides and peptide derivatives have great potential to generate powerful new therapies in regenerative medicine. The high signaling capacity and therapeutic efficacy of peptidic scaffolds has been established in several animal models, and the development of more complex, hierarchical structures based on peptide materials is underway. This highlight discusses several classes of self-assembling peptide-based materials, including peptide amphiphiles, Fmoc-peptides, self-complementary ionic peptides, hairpin peptides, and others. The self-assembly designs, bioactive signalling strategies, and cell signalling capabilities of these bioactive materials are reported. The future challenges of the field are also discussed, including short-term goals such as integration with biopolymers and traditional implants, and long term goals, such as immune system programming, subcellular targeting, and the development of highly integrated scaffold systems.

Fig. 1

A) Chemical structure of a peptide amphiphile, schematic representation of PA self-assembly into cylindrical nanofibers, and cryogenic transmission electron microscopy (cryoTEM) of assembled aggregates. Reprinted with permission from reference (Copyright 2010) and reference (Copyright 2011) B) Chemical structure of a β-hairpin peptide and mechanism of folding and gelation. Reprinted with permission from reference (Copyright 2009 American Chemical Society). C) Chemical structure of a multidomain peptide, mechanism of folding and gelation, and cryoTEM image of assembled peptides. Reprinted with permission from reference (Copyright 2009 American Chemical Society). D) Chemical structure of self-assembling peptide P₁₁-II, its β-sheet-driven assembly into tape-like aggregates, and negatively stained TEM image of the nanostructures. Reprinted with permission from reference (Copyright 2003 American Chemical Society).

Fig. 2

A) Chemical structure of diacetylene-containing PA. B) Photoinitiated topochemical polymerization of diacetylene units. C and D) AFM image of unirradiated (C) and irradiated (D) PA nanofibers. E) Digital images of PA samples showing (1) PA solution without irradiation, (2) gelled PA solution without irradiation, (3) PA solution after irradiation, and (4) gelled PA solution after irradiation. Reprinted with permission from reference (Copyright 2008 American Chemical Society).

Fig. 3

A) Chemical structure of Fmoc-FF and Fmoc-RGD peptides. B) AFM height image of self-assembled Fmoc-peptides. C and D) Fluorescence image of human adult dermal fibroblasts in Fmoc-FF/RGD gel (C) and Fmoc-FF/RGE gel (D) with nuclear staining (DAPI, blue) and actin staining (phalloidin, green). Reprinted from reference with permission from Elsevier.

Fig. 4

A) Chemical structure of drug releasing PA, with the hydrazone linker shown in red and the drug (nabumetone) shown in blue. B) conventional TEM of nabumetone-containing PA containing a hydrolysable hydrazone. C) Profile of nabumetone release from PA gel. Reprinted with permission from reference .

Fig. 5

Aligned monodomain PA gels. A) Birefringence images of two aligned PA noodles, showing light extinction at the crosspoint. B) Scanning electron microscopy (SEM) image of aligned bundles. C) Phase image of human mesenchymal stem cells (hMSCs) preferentially aligned along the string axis. D) Fluorescence image of calcein-stained hMSCs cultured in the aligned PA gel. Reproduced with permission from reference .

Fig. 6

Vision for the future of peptide-based materials in regenerative medicine.