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

Highly Stretchable and Notch-Insensitive Hydrogel Based on Polyacrylamide and Milk Protein

Protein-based hydrogels have received attention for biomedical applications and tissue engineering because they are biocompatible and abundant. However, the poor mechanical properties of these hydrogels remain a hurdle for practical use. We have developed a highly stretchable and notch-insensitive hydrogel by integrating casein micelles into polyacrylamide (PAAm) networks. In the casein-PAAm hybrid gels, casein micelles and polyacrylamide chains synergistically enhance the mechanical properties. Casein-PAAm hybrid gels are highly stretchable, stretching to more than 35 times their initial length under uniaxial tension. The hybrid gels are notch-insensitive and tough with a fracture energy of approximately 3000 J/m². A new mechanism of energy dissipation that includes friction between casein micelles and plastic deformation of casein micelles was suggested

Water-Floating Giant Nanosheets from Helical Peptide Pentamers

One of the important challenges in the development of protein-mimetic materials is understanding the sequence-specific assembly behavior and dynamic folding change. Conventional strategies for constructing two-dimensional (2D) nanostructures from peptides have been limited to using β-sheet forming sequences as building blocks due to their natural tendency to form sheet-like aggregations. We have identified a peptide sequence (YFCFY) that can form dimers <i>via</i> a disulfide bridge, fold into a helix, and assemble into macroscopic flat sheets at the air/water interface. Due to the large driving force for 2D assembly and high elastic modulus of the resulting sheet, the peptide assembly induces flattening of the initially round water droplet. Additionally, we found that stabilization of the helix by dimerization is a key determinant for maintaining macroscopic flatness over a few tens of centimeters even with a uniform thickness of <10 nm. Furthermore, the ability to transfer the sheets from a water droplet to another substrate allows for multiple stacking of 2D peptide nanostructures, suggesting possible applications in biomimetic catalysis, biosensors, and 2D related electronic devices

Revisiting Whitlockite, the Second Most Abundant Biomineral in Bone: Nanocrystal Synthesis in Physiologically Relevant Conditions and Biocompatibility Evaluation

The synthesis of pure whitlockite (WH: Ca₁₈Mg₂(HPO₄)₂(PO₄)₁₂) has remained a challenge even though it is the second most abundant inorganic in living bone. Although a few reports about the precipitation of WH in heterogeneous phases have been published, to date, synthesizing WH without utilizing any effects of a buffer or various other ions remains difficult. Thus, the related research fields have encountered difficulties and have not been fully developed. Here, we developed a large-scale synthesis method for pure WH nanoparticles in a ternary Ca(OH)₂–Mg(OH)₂–H₃PO₄ system based on a systematic approach. We used excess Mg²⁺ to impede the growth of hydroxyapatite (HAP: Ca₁₀(PO₄)₆(OH)₂) and the formation of other kinetically favored calcium phosphate intermediate phases. In addition, we designed and investigated the synthesis conditions of WH under the acidic pH conditions required to dissolve HAP, which is the most thermodynamically stable phase above pH 4.2, and to incorporate the HPO₄^2– group into the chemical structure of WH. We demonstrated that pure WH nanoparticles can be precipitated under Mg²⁺-rich and acidic pH conditions without any intermediate phases. Interestingly, this synthesized nano-WH showed comparable biocompatibility with HAP. Our methodology for determining the synthesis conditions of WH could provide a new platform for investigating other important precipitants in aqueous systems

Tailoring a Tyrosine-Rich Peptide into Size- and Thickness-Controllable Nanofilms

Self-assembled nanostructures of tyrosine-rich peptides have a number of potential applications such as biocatalysts, organic conducting films, and ion-selective membranes. In modulating a self-assembly process of peptides, the interfacial force is an important factor for kinetic control. Here, we present the formation of large-sized and thickness-controllable nanofilms from the YYACAYY peptide sequence (Tyr-C7mer peptide) using Langmuir–Blodgett and Langmuir–Schaefer deposition methods. The Tyr-C7mer peptide showed typical surfactant-like properties, which were demonstrated via the isotherm test (surface pressure–area) by spreading the Tyr-C7mer peptide solution onto an air/water interface. Uniform and flat peptide nanofilms were successfully fabricated and characterized. The redox activity of densely packed tyrosine moieties on the peptide nanofilm was also evaluated by assembling silver nanoparticles on the nanofilm without requiring any additives