The GAIIG sequence, common to the amyloid beta peptide (residues 29–33) and to the HIV‐1 gp120 (residues 24–28 in a typical V3 loop), self‐assembles into amyloid fibrils, as suggested by theory and the experiments presented here. The longer YATGAIIGNII sequence from the V3 loop also self‐assembles into amyloid fibrils, of which the first three and the last two residues are outside the amyloid GAIIG core. We postulate that this sequence, with suitably selected modifications at the flexible positions, can serve as a designable scaffold for novel amyloid‐based materials. Moreover, we report the single crystal X‐ray structure of the beta‐breaker peptide GAIPIG at 1.05 Å resolution. The structural information provided in this study could serve as the basis for structure‐based design of potential inhibitors of amyloid formation.

Antimicrobial resistance (AMR) poses a significant global health risk as a consequence of misuse of antibiotics. Owing to the increasing antimicrobial resistance, it became imperative to develop novel molecules and materials with antimicrobial properties. Porphyrins and metalloporphyrins are compounds which present antimicrobial properties especially after irradiation. As a consequence, porphyrinoids have recently been utilized as antimicrobial agents in antimicrobial photodynamic inactivation in bacteria and other microorganisms. Herein, we report the encapsulation of porphyrins into peptide hydrogels which serve as delivery vehicles. We selected the self-assembling Fmoc-Phe-Phe dipeptide, a potent gelator, as a scaffold due to its previously reported biocompatibility and three different water-soluble porphyrins as photosensitizers. We evaluated the structural, mechanical and in vitro degradation properties of these hydrogels, their interaction with NIH3T3 mouse skin fibroblasts, and we assessed their antimicrobial efficacy against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) bacteria. We found out that the hydrogels are cytocompatible and display antimicrobial efficiency against both strains with the zinc porphyrins being more efficient. Therefore, these hydrogels present a promising alternative for combating bacterial infections in the face of growing AMR concerns.

Copper and zinc nanoparticles have been suggested as potent anticancer agents, particularly against osteosarcoma, a highly aggressive bone cancer with limited treatment options. In order to avoid systemic toxicity, biomolecular carriers able to chelate metal ions and deliver them in a targeted manner to the vicinity of cancer cells need to be developed. Herein, we have used a histidine-containing, cyclic dipeptide as a carrier able to chelate stabilized copper and zinc nanoparticles. The cyclic peptide cyclo-(histidine-phenylalanine) (cHF) self-assembled into amyloid-type fibrils; morphological and structural characterization following metal addition confirmed the formation of cHF−CuNPs and cHF–ZnNPs. These composite nanoparticles demonstrated bacteriostatic activity against Escherichia coli and Staphylococcus aureus at the in vitro level. We evaluated the optimal concentration of cHF–metalNP complexes with limited cytotoxicity to L929 fibroblasts and high cytotoxic effects against MG-63 osteosarcoma cells. Their cytotoxicity was particularly pronounced at pH 6.4, which emulates the tumor microenvironment. The cHF peptide alone did not demonstrate significant antimicrobial or cytotoxic effects to both cell types, suggesting that it can act as a cytocompatible, pH-responsive carrier of metal ions with targeted dual functionality against both microbial infections and osteosarcoma cancer cells.

Emerging neurotrophin treatments for optic nerve injury (ONI) aim to prevent the loss of retinal ganglion cells (RGCs) and enhance axonal regeneration. Microneurotrophins (MNTs), small‐molecule mimetics of neurotrophins, have shown neuroprotective effects in various animal models of neurodegeneration, yet MNT effects on ONI remain unknown. Here, we study the effects of BNN27, a MNT that mimics NGF, in a mouse model of optic nerve crush (ONC) and compare the targeted administration via biomaterial grafts placed around the ONC lesion against standard eye drop delivery. Compared to eye drop delivery, targeted biomaterial‐based BNN27 delivery resulted in more consistent and efficient RGC neuroprotection and reduced microglia‐mediated inflammation in the ONC lesion. Our findings demonstrate that targeted delivery of MNTs can alleviate key consequences of ONI and, therefore, be an essential part of effective combinatorial ONI treatments.

Two-photon polymerization (2PP) enables the fabrication of complex 3D scaffolds for tissue engineering, yet the lack of biocompatible and bioactive photoinitiators remains a bottleneck for functional bio-manufacturing. Here, a one-step strategy is presented using curcumin (CUR), a naturally derived polyphenol, as a high-efficiency multifunctional photoinitiator for gelatin methacryloyl (GelMA) hydrogels. Nonlinear optical characterization reveals a synergistic interaction between CUR and the GelMA protein backbone, resulting in a significantly enhanced two-photon absorption cross-section (σ ≈ 1500 GM) that outperforms conventional initiators. This synergy facilitates an exceptionally broad processing window and high-speed fabrication (up to 52 mm/s) of high-fidelity, complex triply periodic minimal surface (TPMS) and biomimetic bone-like scaffolds. Beyond its initiation efficiency, CUR imparts intrinsic multifunctionality to the resulting 3D constructs. The scaffolds exhibit exceptional biocompatibility with mesenchymal stem cells while demonstrating a potent dual-action antimicrobial defense: a selective passive antifouling effect against E. coli and active photodynamic eradication (>99.9%) of S. aureus upon blue LED irradiation. This "all-in-one" approach transforms the photoinitiator from an inert processing tool into a source of intrinsic scaffold bioactivity, eliminating the need for complex post-fabrication functionalization.