Loic Hilliou

Peptide-based supramolecular hydrogels have emerged as promising biomaterials due to inherent biocompatibility, tunable self-assembly, and structural similarity to the extracellular matrix. This work describes the design, synthesis and characterization of a library of symmetrical bolaamphiphiles based on dehydropeptides, systematically varying both the dehydroamino acid residue and the linker. Aromatic and aliphatic dicarboxylic acids with distinct rigidities were employed to elucidate their influence on molecular self-assembly, hydrogelation, and functional performance. Hydrogel formation was triggered using a pH-responsive approach, and critical aggregation and gelation concentrations were determined. Morphological analysis by transmission electron microscopy revealed dense fibrillar networks with nanometer-scale fiber diameters, while rheological studies demonstrated viscoelastic behavior, tunable mechanical strength, and, in selected systems, efficient self-healing properties. The incorporation of phenylalanyldehydrophenylalanine significantly enhanced hydrogel formation, highlighting the importance of π–π interactions and hydrophobicity. Biological evaluation using HaCaT keratinocytes confirmed low cytotoxicity across the series. A representative injectable hydrogel exhibited sustained release of the anticancer drug methotrexate, governed predominantly by Fickian diffusion. These results establish clear structure–property–function relationships and demonstrate the potential of symmetrical bolaamphiphilic dehydropeptides as versatile platforms for controlled drug delivery.

Bioadhesive materials capable of operating under aqueous conditions are of considerable interest for biomedical and materials science applications. Peptide-based systems represent an attractive platform for such materials due to their structural tunability, inherent biocompatibility, and ability to form supramolecular networks through noncovalent interactions. In this work, a focused library of tyrosine-containing dehydropeptides was designed and synthesized to investigate how molecular architectures influence self-assembly, hydrogel formation and adhesive properties. The peptides were synthesized using a solution-phase Boc strategy and systematically varied with respect to N-terminal protection and C-terminal functionality. The N-protected dehydropeptides formed supramolecular hydrogels through multiple gelation triggers, including pH reduction and heating–cooling cycles. Rheological characterization confirmed the formation of viscoelastic networks with tunable mechanical properties, with storage moduli reaching tens of kilopascals depending on peptide structure. Scanning electron microscopy revealed dense fibrous nanostructures consistent with supramolecular hydrogel formation. The N,C-deprotected dehydropeptides displayed reduced gelation propensity but formed cohesive films with measurable adhesive performance toward hydrophilic substrates. Lap-shear tests demonstrated high shear strengths for the hydrophilic films, highlighting their structural robustness under stress. Overall, this study provides insights into the structure–property relationships governing tyrosine-containing dehydropeptide assemblies and demonstrates their potential as minimalistic building blocks for supramolecular adhesive materials.

Limited mechanical robustness and prompt proteolytic degradation preclude wider biomedical application of supramolecular peptide hydrogels. Low-molecular-weight dehydropeptides represent a promising class of hydrogelators, owing to their enhanced proteolytic stability, high self-assembly propensity, biocompatibility, and tunable rheological and drug-release properties. Herein, we prepared a small library of N-succinylated dehydrotripeptides (Suc-L-Xaa-L-Phe-Z-ΔPhe-OMe/-OH; Xaa = Phe or Val), together with the canonical analogs (Suc-L-Phe-L-Phe-L-Phe-OMe/-OH), to assess whether in addition to proteolytic resistance, dehydropeptides offer clear advantages over canonical peptides in terms of self-assembly, gelation efficacy, mechanical performance, and cargo release. Peptide self-assembly, hydrogel formation, and supramolecular organization were investigated by fluorescence and circular dichroism (CD) spectroscopy, molecular dynamic (MD) simulations, Thioflavin T hydrogel staining, ATR-FTIR spectroscopy, transmission electron microscopy (TEM), and rheological measurements. Drug-release performance was evaluated using methyl orange as a model cargo. Overall, the dehydropeptide-based hydrogels displayed enhanced gelation efficacy, improved mechanical properties, and sustained release profiles compared to canonical analogs. Spectroscopic analysis (CD and ATR-FTIR) and molecular dynamic simulations indicated that the dehydropeptides preferentially self-assemble into more ordered supramolecular fibrils, with extended β-sheet-like packing, whereas the canonical peptides predominantly populate more disordered backbone environments. Proteolysis assays with α-chymotrypsin revealed that both canonical and dehydropeptide methyl esters underwent chymotrypsin-catalyzed ester hydrolysis. Importantly, only the canonical dicarboxylic acid underwent further proteolytic degradation. The dehydropeptide dicarboxylic acids revealed fully resistant to proteolysis over extended time periods. These results demonstrate that the incorporation of dehydroamino acid into peptides enables control over supramolecular packing, nanofibrillar network architecture, rheology, and cargo release. This report raises the profile of relatively underexplored dehydropeptide-based soft materials as promising high-performance biomaterials for technological and biomedical applications.

This study investigated the characterization and application of organoclay formulations in a chemoautotrophic biofloc system. Organoclays were produced using the calcination method and bentonite, chitosan, corn, and tapioca starches as ingredients. Thermogravimetric analysis confirmed the high thermal stability of bentonite, whereas biopolymers (tapioca, chitosan, and corn starch) exhibited greater thermal sensitivity and a lower residual mass. Scanning electron microscopy revealed that organoclays had increased porosity (4–21 µm) compared to bentonite, while energy-dispersive spectroscopy confirmed the retention of key chemical elements. X-ray diffraction and Fourier-transform infrared spectroscopy indicated structural modifications due to thermal processing. In aqueous conditions, bentonite and organoclays disaggregated into particles with sizes between 0.76 and 1.24 μm. Based on these physicochemical properties, three formulations were selected for nitrification trials due to their stability in water, O1 (bentonite + tapioca), O2 (bentonite + tapioca + chitosan), and O6 (bentonite + corn starch), along with a 100% bentonite treatment and a control group (C) supplemented with inorganic salts and artificial Needlona^® substrates. All treatments achieved full nitrification within 37 days, with O1 exhibiting the best performance by maintaining ammonia and nitrite levels within safe thresholds. These findings suggest that organoclays, particularly O1, can enhance nitrification stability, providing a promising strategy for water quality management in intensive aquaculture systems.

The growing demand for sustainable materials is driving both academia and industry to replace conventional oil-based polymers with biodegradable alternatives