In this study, we use modified cationic nanocarriers as vehicles for the intracellular delivery of therapeutic siRNA. After developing nanocarrier formulations with appropriate pKa, size, swellability, and cytocompatibility, we investigated the importance of siRNA loading methods by studying the impact of the pH and time over which siRNA is loaded into the nanocarriers. We concentrate on diffusion-based loading in the presence and absence of electrostatic interactions. siRNA release kinetics were studied using samples prepared from nanocarriers loaded by both mechanisms. In addition, siRNA delivery was evaluated for two formulations. While previous studies were conducted with samples prepared by siRNA loading at low pH values, this research provides evidence that loading conditions of siRNA affect the release behavior. This study concludes that this concept could prove advantageous for eliciting prolonged intracellular release of nucleic acids and negatively charged molecules, effectively decreasing dose frequency and contributing to more effective therapies and improved patient outcomes. In addition, our findings could be leveraged for enhanced control over siRNA release kinetics, providing novel methods for the continued optimization of cationic nanoparticles in a wide array of RNA interference-based applications.

This study explores the synthesis and modification of poly(N-vinylformamide-co-N-hydroxyethyl acrylamide) (poly(NVF-co-HEA)) hydrogels for cosmetic applications. Poly(NVF-co-HEA) hydrogels were produced followed by an acid hydrolysis reaction to produce poly(NVF-co-VAm-co-HEA) hydrogels, introducing poly(vinyl amine) (PVAm) into the structure. This modification considerably alters the hydrogels\' properties, yielding materials with over 96% water content, predominantly in the form of non-freezing or free water, which is beneficial in the uptake and release of hydrophilic species. The primary amine groups from inclusion of VAm also improved the mechanical properties, as evidenced by an 8-fold increase in Young\'s modulus. The hydrogels also possessed pH-responsive behavior, which was particularly noticeable under acidic and basic conditions, where a large decrease in water content was observed (40% to 75% reduction). Characterizing the hydrogels\' release capabilities involved using organic dyes of different functional groups and sizes to examine the pH impact on release. The results indicated that hydrolyzed hydrogels interacted more effectively with charged species, highlighting their suitability for pH-responsive delivery. The release of cosmetic active ingredients was also demonstrated through the controlled release of Liquid Azelaic™, specifically potassium azeloyl diglycinate (PAD). Our findings reveal that the hydrolyzed hydrogels exhibit superior burst release, especially under alkaline conditions, suggesting their suitability for cosmetic applications where controlled, pH-responsive delivery of active ingredients is desired. Overall, this investigation highlights the potential of hydrolyzed poly(NVF-co-HEA) hydrogels in cosmetic applications. Their ability to combine high water content with mechanical integrity, along with their pH-responsive release ability, allows for use in cosmetic formulations.

The wound therapy based on antibiotic delivery inevitably leads to the emergence of drug resistance. Hydrogel biomaterials with inherent antibacterial activities have emerged as promising candidates for addressing this issue. However, developing an inherently antibacterial hydrogel through simple and facile strategies to promote localized wound infection healing remains a challenge. In this study, we successfully constructed antimicrobial cationic hydrogels with self-healing and injectable properties through physically and chemically dual-crosslinked networks. The networks were formed by the copolymers poly[(di(ethylene glycol) methyl ether methacrylate)-co-(4-formylphenyl methacrylate)-co-(2-(methacryloyloxy)ethyl]trimethylammonium chloride solution)] (PDFM) and poly[(di(ethylene glycol) methyl ether methacrylate)-co-(2-aminoethyl methacrylate hydrochloride)-co-(2-(((6-(6-methyl-4[1H]pyrimidionylureido) hexyl)carbamoyl)oxy)ethyl methacrylate)] (PDAU). The hydrogel systems effectively facilitate the regeneration and healing of infected wounds through the contact bactericidal feature of quaternary ammonium cations. The presence of Schiff base bonds in the injectable hydrogels imparts remarkable pH responsiveness and self-healing properties. In vitro experiments verified their intrinsic antibacterial activities along with their favorable cytocompatibility and hemocompatibility in both in vitro and in vivo. In addition, the hydrogel significantly accelerated the healing of bacterially infected in a full-thickness skin wound. This facilely prepared dual-crosslinked hydrogel, without antibiotics loading, holds significant prospects for treating infected wounds.

Cationic gels have seen increasing interest in recent years for 2D cell cultivation since they may represent an alternative to the well-known RGD-peptide motif functionalized gels. However, few hydrogel systems with adjustable cationic strength have been fabricated and investigated so far. In this work, eight gels with defined concentrations of cationic groups, two of which also contained the RGD peptide, were prepared from three well-defined, soluble precursor copolymers with thiol-functionalities and PEGDA3500 as a crosslinker via thiol-ene chemistry. Live/dead stainings of U-251-MG cells on the hydrogels with different concentrations of the cationic motif were made after 3 days and 7 days of cultivation. The results show a high dependence of the number of adhesive cells and their morphology, cluster versus spread cells, on the concentration of cationic groups in the gel. This effect was more pronounced when the gels were not further dialyzed before usage. In addition, a synergistic effect of the two motifs, cationic group and RGD peptide, could be demonstrated, which together induce stronger cell adhesion than either motif alone.

Bacterial infections are a common problem associated with wound treatment that imposes a significant burden on healthcare systems and patients. As a result, healthcare providers urgently need new treatment strategies to protect people. Hydrogel biomaterials with inherent antimicrobial properties offer an attractive and viable solution to this issue. Here, for the first time, we have developed a new efficient synthetic strategy to prepare cationic hydrogels (PHCI) with intrinsically efficient antimicrobial properties by chemically cross-linking trans-1,4-cyclohexanediamine with 1,3-dibromo-2-propanol using a condensation reaction without the use of toxic cross-linking agents. As expected, the prepared PHCI hydrogel possessed an inherent antibacterial ability that can adsorb and kill Staphylococcus aureus and Escherichia coli electrostatically. Notably, in vivo experiments on normal and diabetic rat models confirmed that the PHCI hydrogel can quickly stop bleeding, efficiently kill bacteria, promote the conversion of macrophages from the proinflammatory M1 phenotype to the repaired M2 phenotype, and accelerate collagen deposition and blood vessel formation, thereby achieving rapid wound healing. Overall, this work presents an effective antibacterial dressing that might provide a facile but effective approach for clinical wound management.

Solar-driven steam generation has been recognized as a sustainable and low-cost solution to freshwater scarcity using abundant solar energy. To harvest freshwater, various interfacial evaporators with rational designs of photothermal materials and structures have been developed concentrating on increasing the evaporation rate in the past few years. However, pathogenic microorganism accumulation on the evaporators by long-duration contact with natural water resources may lead to the deterioration of water transportation and the reduction of the evaporation rate. Here, we develop cationic photothermal hydrogels (CPHs) based on [2-(methacryloyloxy)ethyl]trimethylammonium chloride (METAC) and photothermal polypyrrole (PPy) with bacteria-inhibiting capability for freshwater production via solar-driven steam generation. A rapid water evaporation rate of 1.592 kg m-2 h-1 under simulated solar irradiation is achieved with CPHs floating on the water surface. Furthermore, we find that CPHs possess nearly 100% antibacterial performance against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The significant bacteria-inhibiting capability is mainly attributed to the large number of ammonium groups on the CPH network. Moreover, we show that CPHs exhibit good applicability with stable evaporation in natural lake water over 2 weeks, and the number of bacteria in purified lake water is significantly reduced. The device based on CPHs can achieve ∼0.49 kg m-2 h-1 freshwater production from lake water under natural sunlight. This study provides an attractive strategy for the evaporator to inhibit biological contamination and a potential way for long-term stable freshwater production from natural water resources in practical application.

This article reports the behavior of embryonic neural stem cells on a hydrogel that combines cationic, non-specific cell adhesion motifs with glycine-arginine-glycine-aspartic acid-serine-phenylalanine (GRGDSF)-peptides as specific cell adhesion moieties. Therefore, three hydrogels are prepared by free radical polymerization that contains either a GRGDSF-peptide residue (P1), amino ethylmethacrylate as a cationic residue (P2), or a combination of both motifs (P3). For each gel, cross linker concentrations of 8 mol% is used to have a comparable gel stiffness of 8-9 kPa. The cell experiments indicate a synergistic effect of the non-specific, cationic residues, and the specific GRGDSF-peptides on embryonic neural stem cell behavior that is especially pronounced in the cell adhesion experiments by more than doubling the number of cells after 72 h when comparing P3 with P2 and is less pronounced in the proliferation and differentiation experiments.