Biomacromolecules最新文献

Myocardial infarction (MI) remains one of the leading causes of mortality worldwide, necessitating advanced therapeutic strategies to address the resulting electrical disconnection and pathological remodeling. This study developed a conductive hydrogel by covalently cross-linking silk fibroin and hyaluronic acid, integrating MXene nanosheets to mimic the extracellular matrix (ECM). Results demonstrated that the incorporation of MXene significantly enhanced the hydrogel’s conductivity, with SH-M5 exhibiting the highest conductivity of 0.32 S/m. The SH-M5 hydrogel effectively improved electrical signal transmission and enhanced the recovery of the left ventricular function in myocardial infarction. These findings underscore the transformative role of MXene in enhancing the functional properties of hydrogels for myocardial repair. The conductive hydrogel demonstrated a unique capacity to integrate mechanical reinforcement, electrical conductivity, and biocompatibility, presenting a promising platform for treating myocardial infarction and advancing regenerative medicine.

Biomedical device-related bacterial infections are a leading cause of mortality, and traditional antibiotics contribute to resistance. Various surface modification strategies have been explored, but effective clinical solutions remain limited. This study introduces a novel antibacterial nanocoating with copper nanoparticles (CuNPs) that triggers localized nitric oxide (NO) release. The multilayered nanocoating is created using branched polyethylenimine (BPEI) and poly(acrylic acid) (PAA) via a Layer-by-Layer assembly method. CuNP-decorated nanocoatings are formed by reducing copper ions coordinated with amine/carboxylic acid groups. In a physiological environment, CuNPs oxidize to Cu(I), promoting NO release from endogenous NO donors. The nanocoating's thickness is adjustable to regulate amount of CuNPs and NO flux. The optimal thickness for effective NO release against Staphylococcus aureus and Pseudomonas aeruginosa is identified, preventing microbial adhesion and biofilm formation. Importantly, the coating remains cytocompatible due to minimal CuNPs, physiological NO levels, and stable coating properties under physiological conditions.

Combining an amphiphilic block copolymer polybutadiene-b-poly(ethylene glycol) (PBD-b-PEO), an ionizable lipid, a helper lipid, and cholesterol produces thermostable BNPs. Luciferase mRNA-BNPs can be stored for over 1 year at 4 °C with no evidence of degradation to the mRNA or nanocarrier. In vivo, mRNA-BNPs exhibit a greater affinity for secondary lymphoid organs than mRNA-lipid nanoparticles (LNPs) and are efficiently taken up by macrophages and dendritic cells. Freshly fabricated ovalbumin (OVA) mRNA-BNPs elicit robust OVA-specific IgG and functional memory CD8⁺ T cells that persist for at least 5 months. Immunogenicity remains intact after 24 weeks of storage at 4 °C. Anti-PEG antibodies are not boosted by the repeated administration of mRNA-BNPs, unlike mRNA-LNPs. Syrian hamsters vaccinated with SARS-CoV-2 spike mRNA-BNPs are protected against weight loss associated with infection and potently suppress pulmonary viral loads. Protective efficacy is comparable to that conferred by a Comirnaty biosimilar. Cumulatively, mRNA-BNPs are thermostable, immunogenic and possess the potential for clinical application.

Antimicrobial photodynamic therapy (APDT) is a promising alternative to inactivating resistant microorganisms. Metallic phthalocyanines (Pc) substituted with coumarin groups exhibit favorable photophysical properties for APDT; however, their hydrophobicity limits administration. This study investigates indium(III) Pc substituted with 7-oxy-3-(3',4',5'-trimethoxyphenyl)coumarin at nonperipheral (3nInOAc) and peripheral (4nInOAc) positions, both in their free form and encapsulated in polyhydroxybutyrate nanoparticles, for the photodynamic inactivation of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA) bacteria. The photodynamic activity was also assessed through the photooxidation of tryptophan and bovine serum albumin. Theoretical calculations and molecular docking were performed to corroborate the experimental results, investigating the influence of molecular structure on the photodynamic and antimicrobial performance of Pc-loaded nanoparticles as well as their nanoparticulate properties. Overall, both free and encapsulated Pc were capable of photooxidizing biomolecules and exhibited moderate antimicrobial activity, with 4nInOAc demonstrating superior efficacy, achieving an average reduction of 2 logs (99%) in MSSA and MRSA colonies.

Combining an amphiphilic block copolymer polybutadiene-b-poly(ethylene glycol) (PBD-b-PEO), an ionizable lipid, a helper lipid, and cholesterol produces thermostable BNPs. Luciferase mRNA-BNPs can be stored for over 1 year at 4 °C with no evidence of degradation to the mRNA or nanocarrier. In vivo, mRNA-BNPs exhibit a greater affinity for secondary lymphoid organs than mRNA-lipid nanoparticles (LNPs) and are efficiently taken up by macrophages and dendritic cells. Freshly fabricated ovalbumin (OVA) mRNA-BNPs elicit robust OVA-specific IgG and functional memory CD8⁺ T cells that persist for at least 5 months. Immunogenicity remains intact after 24 weeks of storage at 4 °C. Anti-PEG antibodies are not boosted by the repeated administration of mRNA-BNPs, unlike mRNA-LNPs. Syrian hamsters vaccinated with SARS-CoV-2 spike mRNA-BNPs are protected against weight loss associated with infection and potently suppress pulmonary viral loads. Protective efficacy is comparable to that conferred by a Comirnaty biosimilar. Cumulatively, mRNA-BNPs are thermostable, immunogenic and possess the potential for clinical application.

Biomedical device-related bacterial infections are a leading cause of mortality, and traditional antibiotics contribute to resistance. Various surface modification strategies have been explored, but effective clinical solutions remain limited. This study introduces a novel antibacterial nanocoating with copper nanoparticles (CuNPs) that triggers localized nitric oxide (NO) release. The multilayered nanocoating is created using branched polyethylenimine (BPEI) and poly(acrylic acid) (PAA) via a Layer-by-Layer assembly method. CuNP-decorated nanocoatings are formed by reducing copper ions coordinated with amine/carboxylic acid groups. In a physiological environment, CuNPs oxidize to Cu(I), promoting NO release from endogenous NO donors. The nanocoating’s thickness is adjustable to regulate amount of CuNPs and NO flux. The optimal thickness for effective NO release against Staphylococcus aureus and Pseudomonas aeruginosa is identified, preventing microbial adhesion and biofilm formation. Importantly, the coating remains cytocompatible due to minimal CuNPs, physiological NO levels, and stable coating properties under physiological conditions.

Antimicrobial photodynamic therapy (APDT) is a promising alternative to inactivating resistant microorganisms. Metallic phthalocyanines (Pc) substituted with coumarin groups exhibit favorable photophysical properties for APDT; however, their hydrophobicity limits administration. This study investigates indium(III) Pc substituted with 7-oxy-3-(3′,4′,5′-trimethoxyphenyl)coumarin at nonperipheral (3nInOAc) and peripheral (4nInOAc) positions, both in their free form and encapsulated in polyhydroxybutyrate nanoparticles, for the photodynamic inactivation of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA) bacteria. The photodynamic activity was also assessed through the photooxidation of tryptophan and bovine serum albumin. Theoretical calculations and molecular docking were performed to corroborate the experimental results, investigating the influence of molecular structure on the photodynamic and antimicrobial performance of Pc-loaded nanoparticles as well as their nanoparticulate properties. Overall, both free and encapsulated Pc were capable of photooxidizing biomolecules and exhibited moderate antimicrobial activity, with 4nInOAc demonstrating superior efficacy, achieving an average reduction of 2 logs (99%) in MSSA and MRSA colonies.

Wound healing remains a global challenge for clinical and experimental research. Hydrogels prepared from natural polysaccharides show great potential in the wound healing process. In this study, novel hydrogels (G-GLP) were prepared using oxidized Ganoderma lucidum polysaccharides (OGLPs) and carboxymethyl chitosan via the Schiff base reaction, which did not require the addition of any chemical cross-linking agent. The hydrogels showed excellent mechanical properties and biocompatibility. Moreover, the hydrogels showed superior hemostatic performance in mouse liver trauma and tail amputation models. Importantly, G-GLP improved inflammation by promoting the polarization of the macrophage M2 subtype, inhibiting the M1 subtype and reducing intracellular levels of reactive oxygen species. In vivo experiments demonstrated that G-GLP accelerated healing in a total defect wound model by reducing inflammation and promoting blood vessel repair and collagen deposition. These results demonstrate that G-GLP has potential as an effective wound repair dressing.

Antimicrobial peptides (AMPs) are a class of peptides consisting of cationic amino acid residues and a hydrophobic segment, which have been used as an alternative to antibiotics in treating multidrug-resistant bacteria. However, the relationship among the molecular design, assembled structures, and resultant efficacy remains elusive. Herein, we report a class of constitutionally isomeric AMPs assembled into filaments with similar dimensions. Spectroscopic characterizations demonstrated that subtle changes in the position of amino acids led to dramatic variations in molecular packing and surface charges, which were verified by molecular dynamics simulations. In vitro antibacterial assays showed that all AMPs exerted antibacterial activity against Gram-positive methicillin-resistant Staphylococcus aureus (MRSA), but the efficacy was dependent on the molecular design. Given the good biocompatibility to eukaryotic cells, these AMPs could be potentially used as antibacterial agents. We believe that this finding provides an avenue to tune the bioactivity of AMPs by rational molecular design.

Wound healing remains a global challenge for clinical and experimental research. Hydrogels prepared from natural polysaccharides show great potential in the wound healing process. In this study, novel hydrogels (G-GLP) were prepared using oxidized Ganoderma lucidum polysaccharides (OGLPs) and carboxymethyl chitosan via the Schiff base reaction, which did not require the addition of any chemical cross-linking agent. The hydrogels showed excellent mechanical properties and biocompatibility. Moreover, the hydrogels showed superior hemostatic performance in mouse liver trauma and tail amputation models. Importantly, G-GLP improved inflammation by promoting the polarization of the macrophage M2 subtype, inhibiting the M1 subtype and reducing intracellular levels of reactive oxygen species. In vivo experiments demonstrated that G-GLP accelerated healing in a total defect wound model by reducing inflammation and promoting blood vessel repair and collagen deposition. These results demonstrate that G-GLP has potential as an effective wound repair dressing.