Cooperative Assembly of a Peptide Gelator and Silk Fibroin Afford an Injectable Hydrogel for Tissue Engineering

Abstract

Silk fibroin (SF) from Bombyx mori has received increasing interest in biomedical fields, because of its slow biodegradability, good biocompatibility, and low immunogenicity. Although SF-based hydrogels have been studied intensively as a potential matrix for tissue engineering, weak gelation performance and low mechanical strength are major limitations that hamper their widespread applicability. Therefore, searching for new strategies to improve the SF gelation property is highly desirable in tissue engineering research. Herein, we report a facile approach to induce rapid gelation of SF by a small peptide gelator (e.g., NapFF). Following the simple mixing of SF and NapFF in water, a stable hydrogel of SF was obtained in a short time period at physiological pH, and the minimum gelation concentration of SF can reach as low as 0.1%. In this process of gelation, NapFF not only can behave itself as a gelator for supramolecular self-assembly, but also can trigger the conformational transition of the SF molecule from random coil to β-sheet structure via hydrophobic and hydrogen-bonding interactions. More importantly, for the generation of a scaffold with favorable cell-surface interactions, a new peptide gelator (NapFFRGD) with Arg-Gly-Asp (RGD) domain was applied to functionalize SF hydrogel with improved bioactivity for cell adhesion and growth. Following encapsulating the vascular endothelial growth factor (VEGF), the SF gel was subcutaneously injected in mice, and served as an effective matrix to trigger the generation of new blood capillaries in vivo.

Enhanced Osteogenesis of Bone Marrow‐Derived Mesenchymal Stem Cells by a Functionalized Silk Fibroin Hydrogel for Bone Defect Repair

“…The quick gelation process of SF‐RGD gel was triggered by the cooperative intermolecular interaction assembly of NapFFRGD gelator and SF molecules in water aided by hydrophobic and hydrogen bonding. These interactions can further induce the molecular conformational transformation of SF from random coils to the β‐sheet conformation, thus resulting in its rapid gelation . Rheological tests revealed that the obtained SF‐RGD gel exhibited typical viscoelastic behavior of hydrogels, as exemplified by the threefold higher storage moduli ( G ' = 6679 Pa) of SF‐RGD gel in relation to its loss moduli ( G ” = 1742 Pa) within the investigated oscillating frequency range from 0.1 to 100 Hz (Figure d).…”

“…However, its slow gelation rate and the shortage of biochemical cues to direct cell adhesion, proliferation, and differentiation significantly affects its application potentials in biomedical fields. Therefore, peptide gelators were incorporated into SF to significantly improve its gelation properties through cooperative molecular assembly in liquid phase . In order to generate a SF gel with a high gelation rate and improved biochemical cues, we synthesized NapFFRGD, a small peptide gelator, and introduced it to the SF solution.…”

“…The tailorable properties of biomaterials such as their chemical composition, surface properties, and topographical structures, can act as insoluble exogenous stimuli to promote adhesion and activation of specific cellular signaling pathways, as well as to direct MSC differentiation toward osteoblasts or other lineages . Recently, our group developed novel hydrogels from small peptide gelators containing an RGD ligand and silk fibroin (SF) . Because of their high biocompatibilities, suitable biodegradability, and the presence of RGD ligands within scaffold, the prepared hydrogels were able to function as a biomimetic matrix to promote cell adhesion and proliferation .…”

“…Recently, our group developed novel hydrogels from small peptide gelators containing an RGD ligand and silk fibroin (SF) . Because of their high biocompatibilities, suitable biodegradability, and the presence of RGD ligands within scaffold, the prepared hydrogels were able to function as a biomimetic matrix to promote cell adhesion and proliferation . Moreover, besides acting as cell adhesive peptides, abundant RGD residues on biomaterial surfaces are also responsible for signal transduction and cellular differentiation of MSCs .…”

Green preparation of anti-inflammation an injectable 3D porous hydrogel for speeding up deep second-degree scald wound healing

“…[9][10][11] In early 1960, O. Wichterle et al reported the rst case of hydrophilic gels, 12 many studies have been focused on applications in wound healing via using hydrogels. [13][14][15][16][17][18] Increased evidence showed hydrogels can deliver cytokines and growth factors, 19 which is benecial for burn wound healing. Also, hydrogels are good stain removers, [20][21][22] and they are nonadherent and can engulf bacteria, which is benets to threedimensional (3D) network expansion upon exudate absorption.…”