UV Light-Responsive Peptide-Based Supramolecular Hydrogel for Controlled Drug Delivery.

Low-molecular-weight self-assembled peptides may serve as promising hydrogelators for drug delivery applications by changing their structural network in response to external stimuli. Herein, inspired by the well-studied low-molecular-weight peptide hydrogelator, fluorenyl-methoxycarbonyl-diphenylalanine (Fmoc-FF), a novel peptide is designed and synthesized to include an ultraviolet (UV)-sensitive phototrigger. Similar to Fmoc-FF, 6-nitroveratryloxycarbonyl-diphenylalanine (Nvoc-FF) self-assembles to form a 3D, self-supporting, nanofibrous hydrogel. The Nvoc-FF hydrogel exhibits good mechanical properties with a storage modulus of 40 kPa. UV irradiation of the Nvoc-FF hydrogel encapsulating insulin-fluorescein isothiocyanate (insulin-FITC) results in the cleavage of Nvoc-FF peptide to produce unmasked FF, thereby facilitating the degradation of the hydrogel and the release of insulin-FITC. This release is in linear correlation to the irradiation time. In the present study, a first insight into this rigid, fibrous, light-responsive hydrogel is provided, allowing the fabrication of a novel drug delivery system for controlled release of large molecules.

Arginine-Presenting Peptide Hydrogels Decorated with Hydroxyapatite as Biomimetic Scaffolds for Bone Regeneration.

Hydrogels are promising candidates for biomimetic scaffolds of the extracellular matrix in tissue engineering applications. However, their use in bone tissue engineering is limited due to their low mechanical properties. In this study, we designed and synthesized multicomponent peptide-based hydrogels composed of fluorenyl-9-methoxycarbonyl diphenylalanine (FmocFF), which contributed to the rigidity and stability of the hydrogel, and Fmoc-arginine (FmocR), which mediated high affinity to hydroxyapatite (HAP) due to the arginine moiety. The new hydrogels composed of nanometric fibril networks were decorated with HAP and demonstrated high mechanical strength with a storage modulus of up to 29 kPa. In addition, the hydrogels supported cell adhesion and in vitro cell viability. These properties suggest using these multicomponent organic-inorganic hydrogels as functional biomaterials for improved bone regeneration.

Enhanced Nanoassembly-Incorporated Antibacterial Composite Materials.

The rapid advancement of peptide- and amino-acid-based nanotechnology offers new approaches for the development of biomedical materials. The utilization of fluorenylmethyloxycarbonyl (Fmoc)-decorated self-assembling building blocks for antibacterial and anti-inflammatory purposes represents promising advancements in this field. Here, we present the antibacterial capabilities of the nanoassemblies formed by Fmoc-pentafluoro-l-phenylalanine-OH, their substantial effect on bacterial morphology, as well as new methods developed for the functional incorporation of these nanoassemblies within resin-based composites. These amalgamated materials inhibit and hinder bacterial growth and viability and are not cytotoxic toward mammalian cell lines. Importantly, due to the low dosage required to confer antibacterial activity, the integration of the nanoassemblies does not affect their mechanical and optical properties. This approach expands on the growing number of accounts on the intrinsic antibacterial capabilities of self-assembling building blocks and serves as a basis for further design and development of enhanced composite materials for biomedical applications.

Improving the Mechanical Rigidity of Hyaluronic Acid by Integration of a Supramolecular Peptide Matrix.

Hyaluronic acid (HA), a major component of the extracellular matrix, is an attractive material for various medical applications. Yet, its low mechanical rigidity and fast in vivo degradation hinder its utilization. Here, we demonstrate the reinforcement of HA by its integration with a low-molecular-weight peptide hydrogelator to produce a composite hydrogel. The formulation of HA with the fluorenylmethoxycarbonyl diphenylalanine (FmocFF) peptide, one of the most studied self-assembling hydrogel-forming building blocks, showing notable mechanical properties, resulted in the formation of stable, homogeneous hydrogels. Electron microscopy analysis demonstrated a uniform distribution of the two matrices in the composite forms. The composite hydrogels showed improved mechanical properties and stability to enzymatic degradation while maintaining their biocompatibility. Moreover, the storage modulus of the FmocFF/HA composite hydrogels reached up to 25 kPa. The composite hydrogels allowed sustained release of curcumin, a hydrophobic polyphenol showing antioxidant, anti-inflammatory, and antitumor activities. Importantly, the rate of curcumin release was modulated as a function of the concentration of the FmocFF peptide within the hydrogel matrix. This work provides a new approach for conferring mechanical rigidity and stability to HA without the need of cross-linking, thus potentially facilitating its utilization in different clinical applications, such as sustained drug release.

Molecular co-assembly as a strategy for synergistic improvement of the mechanical properties of hydrogels.

Molecular self-assembly is a key direction for the fabrication of advanced materials. Yet, the physical properties of the formed assemblies are limited by the inherent characteristics of the specific building blocks. Here, we have applied a co-assembly approach to synergistically modulate the mechanical properties of peptide hydrogels, thereby forming extremely stable and rigid hydrogels.