Biomacromolecules最新文献

Knotted proteins are unique biomolecules where backbone entanglement imposes intrinsic constraints on structure and dynamics. The interaction of such a topologically restrained protein with molecular crowders remains unexplored. Using molecular dynamics simulations, we investigate the effects of polyethylene glycol (PEG) and dextran on the structure, interactions, and topological dynamics of the trefoil-knotted enzyme AOTCase. Persistent, heterogeneous accumulation of dextran near the protein surface is observed, whereas PEG exhibits a transient interaction pattern. The distinct interfacial behaviors propagate into the protein’s dynamical organization: dextran induces fragmentation of communication pathways, while PEG largely preserves network coherence. At elevated temperatures, dextran retards global denaturation compared to PEG or pure water, with the knotted core exhibiting reduced fluctuations. Our findings reveal that the effects of molecular crowding on knotted proteins arise from both excluded-volume effects and the chemical nature of crowder-protein interactions. This interplay can influence both local topological dynamics and global stability.

Chronic wounds present clinical challenges due to delayed healing, infection, and immune dysfunction. Most hydrogel dressings rely on crosslinking agents with potential adverse effects. This study introduces a one-pot, dual-crosslinked hydrogel fabricated via a bienzymatic cascade system using chitosan modified with phenol and arginine groups (CPA), xyloglucan (XG), horseradish peroxidase, and galactose oxidase (GalOx). The GalOx oxidizes XG to generate aldehydes, which form Schiff base bonds with the amino groups of CPA, creating the first gel network and releasing H₂O₂. The phenol groups in CPA are then catalyzed by H₂O₂ and HRP to form covalent bonds, establishing the second network. The hydrogel exhibits excellent mechanics, shear-thinning, self-healing, injectability, antimicrobial activity, angiogenesis promotion, and hemostatic properties. It shows superb biocompatibility and accelerates wound healing in burn and diabetic mouse models, outperforming commercial products. This hydrogel is a promising dressing for chronic wound therapy.

This study reports, for the first time, a stable and reproducible semi-continuous bioprocess for the sustained production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) over 98 days, corresponding to 7 consecutive operational repetitions. The process was operated under non-sterile conditions using a cyanobacteria-dominated microbiome and employed acetate and valerate supplementation. Throughout the operation, a consistent 3-hydroxyvalerate (3HV) molar fraction of 8 −12.2 mol % was maintained, with a maximum polymer content of 17.9% of dry cell weight. Notably, reducing the valerate concentration from 100 to 50 mg·L⁻¹ did not compromise PHBV production, indicating the metabolic flexibility of the microbial consortium and highlighting the potential for substrate optimization. Microbial community analysis revealed a strong dominance of Synechocystis sp. (>95%) over Synechococcus sp. (<5%), with the consortium exhibiting resilience to cyclic hypoxic conditions. Transmission electron microscopy, in combination with Nile blue staining, confirmed the intracellular accumulation of PHBV granules within the cyanobacteria cells. Thermal characterization further demonstrated the formation of semi-crystalline PHBV, with characteristic melting transitions spanning 147 −169 °C. Overall, these findings support the potential of cyanobacteria-dominated microbiomes for sustained PHBV production with a relatively stable 3HV molar fraction.

Cellulose aerogels are biocompatible and biodegradable, but their extreme sensitivity to water limits their real-world applications. Effective hydrophobization typically requires high hydrophobe loadings, particularly for high surface area, mesoporous aerogels. Here, we react acid chlorides with surface hydroxy groups of cellulose nanofibril (CNF) gels to graft long-chain esters (C₆/C₁₂/C₁₈). Apolar and/or aprotic solvents like heptane and toluene are preferred. FTIR and solid-state NMR confirm the grafting of ∼0.42/0.29/0.22 esters per d-glucopyranose unit for C₆/C₁₂/C₁₈, respectively, corresponding to ∼19/21/23 wt % hydrophobe. The water contact angle increases from <20° to 125°, with a 350% reduction in humidity uptake and a 90% reduction in humidity-induced shrinkage following esterification. The hydrophobization has no direct effect on thermal conductivity but enables the aerogels to maintain their insulating properties after prolonged humidity exposure. A hydrophobic and superinsulating (18 mW·m⁻¹·K⁻¹) cellulose aerogel was produced by combining esterification and uniaxial compression. The protocol was extended to chitosan and alginate aerogels.

The widespread clinical adoption of implantable devices has driven growing interest in biodegradable alternatives that eliminate the need for secondary removal surgeries. Among these, glycerol-based thermosets have emerged as promising biocompatible materials. Compared with established glycerol-based thermosets, incorporating shorter-chain aliphatic dicarboxylic acids into the glycerol backbone may enhance hydrophilicity and potentially accelerate hydrolytic degradation, while varying the curing conditions enables tailorable properties for biomedical applications requiring temporary structural support. Herein, poly(glycerol glutarate) (GGA) and poly(glycerol adipate) (GAA) were synthesized via solvent- and catalyst-free polycondensation reactions. Variation in curing temperature yielded thermosets with tailorable swelling, degradation, mechanical, and shape-memory properties. The thermosets exhibited hemocompatibility and cytocompatibility, supporting cell growth and proliferation without inducing intracellular oxidative stress. Overall, GGA and GAA thermosets combine tailorable properties with favorable in vitro biological performance, broadening the design space of degradable polyglycerol thermosets for temporary soft-tissue applications requiring tunable mechanical support and rapid resorption.

Thioethers can be oxidized to sulfoxides and sulfones, and such transformation enables facile access to side chains with different extents of oxidation for creating multifunctional sulfur-containing polymers. Herein, a series of discrete oligo(ethylene sulfide)-derived monomers and their corresponding oxidized monomers are synthesized by iterative synthesis, affording discrete oligomers with two or three repeat units. Reversible addition−fragmentation chain transfer (RAFT) polymerization of these monomers gives well-defined polymers featuring discrete thioether, sulfoxide, and sulfone oligomers as side chains, and their thermal stability and glass transition temperature (T_g) are analyzed by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The antifouling properties of these materials are challenged by antifouling assays against the attachment of proteins, bacteria, and human blood cells. Furthermore, the polymer with sulfoxide side chains is water-soluble and exhibits low cytotoxicity against mouse fibroblast cells (NIH/3T3), which holds potential as an alternative hydrophilic material to mitigate severe fouling.

Hypoglycemia remains a major challenge in type-1 diabetes, requiring rapid glucagon delivery; however, current formulations are limited by poor aqueous stability and reconstitution constraints. A stable, injectable glucagon formulation in an aqueous solution could transform treatment, enabling mini-dosing for mild-to-moderate hypoglycemia or continuous infusion in closed-loop systems. Here, we introduce supramolecular poly(trehalose) diblock copolymer nanoparticles via polymerization-induced self-assembly (PISA) to generate distinct nanoparticle morphologies. A cysteine-modified glucagon analogue (Q24C) was conjugated to poly(trehalose methacrylate) coronas via pyridyl disulfide exchange. Glucagon stabilized by vesicles demonstrated enhanced resistance to degradation and fibrillation in aqueous media, maintaining stability for 30 days at 23−24 °C and upon solution heating. Glucagon−vesicle conjugates effectively reversed insulin-induced hypoglycemia in male mice, maintaining glucose-counterregulatory activity after 30 days of storage at 23−24 °C. These findings highlight that polymer-stabilized glucagon nanoformulations overcome longstanding stability barriers while preserving biological activity, offering a robust platform for treating insulin-induced hypoglycemia in type-1 diabetes.

Peripheral nerve injuries often cause long-term functional deficits. This work presents a double-layer nerve guidance tube produced by 3D extrusion printing, combining a PCL-based outer layer with a dextran-based inner hydrogel containing N2a cells. Three PCL/PEGDA formulations (35PCL_2k:65PEGDA, 50PCL_2k:50PEGDA and 40PCL_2k:40PEGDA:20PCL₅₃₀) were developed, enabling scalable fabrication of dextran/PCL conduits while eliminating DMSO use and its associated post-processing. The inner 20Dex:5HAMA:10GelMA hydrogel was optimized through iterative testing. Comprehensive physicochemical, mechanical, and cytotoxic analyses revealed that all PCL-based formulations exhibited similar behavior, with 50PCL_2k:50PEGDA exhibiting superior mechanical strength and cytocompatibility. As expected, 20Dex:5HAMA:10GelMA displayed lower mechanical resistance and faster degradation but strongly supported cell viability and proliferation. Both inks were successfully printed into a bilayer tube that demonstrated high resistance in a suturability test, withstanding the suturing procedure without tearing or deformation. These results highlight the strong potential of this system for future in vivo nerve regeneration studies.

In situ lignin modification via organosolv treatment enhances the thermal softening of wood. However, the influence of diol solvent structures on this process remains unclear. We examined the effects of various diol types on the lignin structure and thermal-softening behavior of organosolv-treated wood using HSQC nuclear magnetic resonance (NMR), thermogravimetry, thermomechanical analysis, and dynamic mechanical analysis. NMR analyses confirmed the grafting of all tested diols onto lignin, while thermal analyses revealed that lignin mobility depended on diol type. Notably, for 1,4-butanediol- and 1,5-pentanediol-treated wood, dynamic elastic modulus (E′) was similar to that of untreated wood at an ambient temperature but decreased sharply upon heating under oven-dry conditions. In contrast, the other diols reduced E′ at an ambient temperature because of a substantial mass loss. These findings indicate that the thermal-softening behavior of wood depends on the balance between lignin modification and component removal and can be controlled by diol selection and treatment optimization.

Sesbania gum (SG) represents a promising polysaccharide feedstock for hydrogels applied in skin tissue engineering, yet its practical utilization is limited by weak mechanical performance, severe molecular self-aggregation and insufficient chemical modifiability. Herein, a SG-derived antibacterial hydrogel (SGEC) with a well-defined three-dimensional porous network was fabricated via a dual-crosslinking route relying on epichlorohydrin covalent crosslinking and subsequent Cu²⁺ metal coordination. Benefiting from this dual-crosslinking design, SGEC possesses adjustable porous architectures and prominent broad-spectrum bactericidal capacity, capable of eradicating pathogenic bacteria at concentrations over 10⁶ CFU/mL, including Escherichia coli, Staphylococcus aureus, Bacillus cereus and Bacillus anthracis. In vivo infected wound assays further verified that SGEC efficiently suppresses wound bacterial colonization, speeds up tissue repair and facilitates complete epidermal regeneration. This work overcomes the inherent drawbacks of neat SG hydrogels and delivers a viable strategy for advancing polysaccharide hydrogels toward clinical biomedical wound treatment.