3D Printing of Self‐Assembling Nanofibrous Multidomain Peptide Hydrogels

Abstract

has been to chemically modify naturallyderived hydrogel materials to make them more printable, while attempting to maintain their favorable biological properties. Recently, two generalizable strategies have been proposed to allow for the printing of a wide range of hydrogel materials, which both include a stabilization method to allow for short term print fidelity, followed by a crosslinking method to impart longterm stability. [36,37] Despite these advances, naturally derived materials suffer from batch to batch variability, frequently require chemical modification to have sufficient mechanical properties, and have predefined bioactivity. [38] A more favorable approach for the creation of new 3D printable inks is to design synthetic materials with specified mechanical, biological, and chemical properties. One class of materials that offers this design freedom is self-assembling peptides (SAPs). [39][40][41][42] SAPs are peptides that assemble into nanostructures due to the orchestration of well-designed supramolecular forces. These nanostructures can then interact in such a way to generate a macroscopic hydrogel. SAPs are easy to synthesize, chemically well-defined, purifiable, and offer design flexibility to achieve a wide range of material properties. In addition, their synthesis is inherently modular, and the properties of SAPs can be altered by simply changing their primary sequence or through the incorporation of bioactive peptide sequences. Because SAPs consist solely of amino acid building blocks, their chemistry and degradation products are biologically friendly, which is a common drawback of hydrogels made from other polymers. Thus, SAPs offer the flexibility of synthetic hydrogel materials, while also maintaining the biocompatibility of naturally derived ones.SAPs are an attractive soft material for extrusion 3D printing because they commonly have shear thinning and rapidly selfhealing properties due to their noncovalent assembly mechanism. [4,43] Despite this, there has been limited 3D printing work involving SAPs. The Hauser lab was the first to demonstrate the 3D printing of SAPs, using tetrapeptides and PBS in a coaxial printing system to create centimeter sized constructs and encapsulate cells. [44,45] Although this work presented multiple breakthroughs, limitations included the use of noncanonical amino acids and limited print fidelity and complexity. The other major work showing the extrusion 3D printing of SAPs, from the Stupp lab, demonstrated the shear alignment of nanofibers using a peptide amphiphile ink. [46] The authors 3D printing has become one of the primary fabrication strategies used in biomedical research. Recent efforts have focused on the 3D printing of hydrogels to create structures that better replicate the mechanical properties of biological tissues. These pose a unique challenge, as soft materials are difficult to pattern in three dimensions with high fidelity. Currently, a small number of biologically derived polymers that form hydrogels are frequently reused for 3D printing ...

Supramolecular gels – a panorama of low-molecular-weight gelators from ancient origins to next-generation technologies

“…35b and c) that were used for cell culture, including creating tumour spheroids (Section 4.7). Recently, Hartgerink and co-workers extrusion-printed peptide hydrogels, 274 with applications in regenerative medicine (Section 4.7).…”

Advanced supramolecular design for direct ink writing of soft materials

“…Based on a very similar principle, Hartgerink et al reported a nanofibrous hydrogel comprised of multidomain peptides with good viscoelastic properties for DIW. 178 The 3D-printed peptide hydrogels demonstrated their bio-computability for cell culturing.…”

Nanoarchitecture-Integrated Hydrogel Systems toward Therapeutic Applications

“…Bioactive peptides can bind noncovalently to produce a diversity of supramolecular assemblages including nanoparticles and nanofibers, thus enhancing in vivo stability and bioavailability. Based on these characters, a large number of supramolecular assemblages have been extensively designed to form hydrogel and integrate with nanoarchitectures for extending bioapplication. − For instance, a self-assembled chelating peptide hydrogel (PPH) was engineered to load with an osteogenic metal ion cluster extracted from the processed pyritum decoction . Since this PPH could regulate a variety of genes related to extracellular matrix synthesis, cell adhesion and migration, and cytokine expression in the process of bone regeneration, PPH would accelerate the progress of various bone healing stages and shorten the bone healing cycle.…”