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Helicobacter pylori is the primary cause of gastric adenocarcinoma, which afflicts more than half of the world's population and seriously affects human health. However, achieving efficient treatment of H. pylori infection by effective drug delivery and bioavailability after oral administration remains a challenge due to the harsh microenvironment, short drug retention time, and physiological barriers in the stomach. Moreover, H. pylori has shown resistance to many clinical antibiotics. Antimicrobial peptides (AMPs) exhibit substantial therapeutic efficacy against H. pylori, while they are not likely to induce drug resistance, suggesting their potential utility for the treatment of diseases related to H. pylori. In this paper, we report the design and synthesis of an AMP (GE33) hydrogel with pH-responsive and controlled peptide release properties, in which the minimal inhibitory concentration of the AMP against H. pylori is as low as 1 µg/mL. GE33 self-assembles into a stable peptide hydrogel under neutral pH conditions but decomposes into monomers or oligomers under acidic conditions. Upon oral administration of the hydrogel, the acidic gastric environment would facilitate rapid release of active AMP molecules from the hydrogel and immediate targeting of H. pylori in the stomach wall. Additionally, the remaining peptide is protected in the hydrogel, extending its retention time in the stomach, so that persistent drug release is achieved. The controlled and sustained release manner of the active molecule GE33, which enhances drug bioavailability, along with its excellent bactericidal efficacy opens a great potential for treating H. pylori infection.

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The development of peptide-based hydrogels characterized by both high biostability and potent antimicrobial activity, aimed at combating multidrug-resistant bacterial infections and providing scaffolds for cell cultures, continues to pose a significant challenge. The susceptibility of antimicrobial peptides (AMPs) to degradation by cations, serum, and proteases restricted their applications in clinical environments. In this study, we designed a peptide sequence (termed D-IK1) entirely consisting of D-amino acids, an enantiomer of a previously reported AMP IK1. Our results demonstrated remarkably improved antibacterial and anticancer activities of D-IK1 as compared to IK1. D-IK1 self-assembled into hydrogels that effectively inhibited bacterial and cancer cell growth by the controlled and sustained release of D-IK1. Importantly, D-IK1 was extremely stable in salt solutions and resisted serum and protease degradation. In addition, the D-IK1 hydrogel fostered cell adhesion and proliferation, proving its viability as a 3D scaffold for cell culture applications. Our research presents a versatile, highly stable antibacterial hydrogel scaffold with potential widespread applications in cell culture, wound healing, and the eradication of multidrug-resistant bacterial infections.

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Perfluorocarbon (PFC) nanodroplets (NDs) are expanding in a wide range of applications in biotechnology and nanotechnology. Their efficacy in biological systems is significantly influenced by their size uniformity and stability within bioelectrolyte contexts. Presently, methods for creating monodisperse, highly concentrated, and well-stabilized PFC NDs under harsh conditions using low energy consumption methods have not been thoroughly developed, and their stability has not been sufficiently explored. This gap restricts their applicability for advanced medical interventions in tissues with high pH levels and various electrolytic conditions. To tackle these challenges and to circumvent potential toxicity from surface stabilizers, we have conducted an in-depth investigation into the formation and stability of uncoated perfluorohexane (PFH) NDs, which were synthesized by using a low-energy consumption solvent exchange technique, across complex electrolyte compositions or a broad spectrum of pH levels. The results indicated that low concentrations of low-valent electrolyte ions facilitate the nucleation of NDs and consistently accelerate Ostwald ripening over an extended period. Conversely, high concentrations of highly valent electrolyte ions inhibit nucleation and decelerate the ripening process over time. Given the similarities between the properties of NDs and nanobubbles, we propose a potential stabilization mechanism. Electrolytes influence the Ostwald ripening of NDs by adjusting the adsorption and distribution of ions on the NDs' surface, modifying the thickness of the electric double layer, and fine-tuning the energy barrier between droplets. These insights enable precise control over the stability of PFC NDs through the meticulous adjustment of the surrounding electrolyte composition. This offers an effective preparation method and a theoretical foundation for employing bare PFC NDs in physiological settings.

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Developing double-network (DN) hydrogels with high mechanical properties and antibacterial efficacy to combat multidrug-resistant bacterial infections and serve as scaffolds for cell culture still remains an ongoing challenge. In this study, an ion-responsive antibacterial peptide (AMP) (C16-WIIIKKK, termed as IK7) was synergistically combined with a photoresponsive gelatin methacryloyl (GelMA) polymer to fabricate a biocompatible DN hydrogel. The GelMA-IK7 DN hydrogel showed enhanced mechanical properties in contrast to the individual IK7 and GelMA hydrogels and demonstrated substantial antibacterial efficacy. Further investigations revealed that the DN hydrogel effectively inhibited bacterial growth by the controlled and sustained release of the IK7 peptide. In addition, the formation of the DN hydrogel was also found to protect AMP IK7 from rapid degradation by proteinase K. Our findings suggested that the developed GelMA-IK7 DN hydrogel holds great potential for next-generation antibacterial hydrogels for three-dimensional cell culture and tissue regeneration.

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The assembly of chiral peptides facilitates the formation of diverse supramolecular structures with unique physicochemical and biological properties. However, the effects of chirality on peptide assembly and resulting hydrogel properties remain underexplored. In this study, we systematically investigated the assembly propensity, morphology, and biostability of mixture of a pair of enantiomeric peptides LELCLALFLF (ECF-5) and DEDCDADFDF (ecf-5) at various ratios. Results indicate the development of ß-sheet fibrils, ultimately leading to the formation of self-supporting hybrid hydrogels. The hydrogel formed at a ratio of 1:1 exhibits a significantly lower storage modulus (G') than of the ratios of 0:1, 1:3, 3:1 and 1:0 (nD/nL; same below). Kink-separated fragments of approximately 100 nm in length predominate at ratios of 1:3 and 3:1, compared with the smooth fibrils at other ratios, probably attributed to an alternating arrangement of the co-assembled and self-assembled peptide fragments. The introduction of ecf-5 to the hybrid hydrogels improves resistance to proteolytic digestion and maintains commendable biocompatibility in both MIN6 and HUVECs cells. These findings provide valuable insights into the development of hydrogels with tailored properties, positing them potential scaffolds for 3D cell culture and tissue engineering.

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Although surgery is the primary method to treat malignant melanoma, it has drawbacks such as residual tumor that could trigger cancer recurrence and wound infections that are especially difficult to heal in diabetics. In this research, we have constructed anti-cancer peptides/polyvinyl alcohol (PVA) double-network (DN) hydrogels for the treatment of melanoma. The maximum stress of the DN hydrogels is found to be larger than 2 MPa, which endows the DN hydrogels with ideal mechanical performance for therapeutic wound dressing. The peptides naphthalene-FIIIKKK (IK1) and phloretic acid-FIIIKKK (IK3) that were previously developed as effective antibacterial peptides, as well as the peptide/PVA DN hydrogels, are found to have good anti-cancer efficacy and target mouse melanoma cells B16-F10 while being nontoxic to normal cells. Further studies have revealed that IK1 and IK3 damage the tumor cell membrane and mitochondrial membrane and eventually trigger apoptosis. In the mouse melanoma model and the diabetic bacterial infection model, the DN hydrogels exhibit great anti-tumor, anti-bacterial, and wound healing promotion abilities in vivo. Because of their excellent mechanical properties, the DN hydrogels are promising soft materials for directly treating malignant melanomas as well as for preventing recurrence and bacterial infection after melanoma surgery that promote wound healing.

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Correction for 'Gram-selective antibacterial peptide hydrogels' by Yangqian Hou et al., Biomater. Sci., 2022, 10, 3831-3844, https://doi.org/10.1039/D2BM00558A.

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The human microbiome plays fundamental roles in human health and disease. However, widely used broad-spectrum antibiotics severely disrupt human-related microbial communities, eventually leading to resistant bacteria, posing a growing threat to global medical health. Antimicrobial peptides (AMPs) are promising antimicrobial agents that barely cause bacterial resistance. Excellent broad-spectrum antimicrobial activities have been achieved using hydrogels self-assembled from AMPs, but there is still a lack of AMP hydrogels that can target Gram-positive and Gram-negative bacteria. Herein, several hydrogels self-assembled from AMPs, termed IK1, IK3, and IK4, were designed and synthesized. In vitro antibacterial results indicated that the IK1 and IK4 hydrogels specifically targeted Gram-positive and Gram-negative bacteria, respectively, while the IK3 hydrogel targeted both Gram-positive and Gram-negative bacteria. The desired broad-spectrum or Gram-selective AMP hydrogels are believed to be obtained through the rational design of the hydrophilicity, hydrophobicity, and charge properties of the peptide molecules. Good in vivo Gram-selective antibacterial properties and the ability to promote wound healing have been demonstrated via treating mouse wound models with these AMP hydrogels. We believe that these Gram-selective AMP hydrogels could potentially have important applications in treating common recurring infections.

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