Biomacromolecules最新文献

As a result of their hierarchical structure and biological processing, silk fibers rank among nature's most remarkable materials. The biocompatibility of silk-based materials and the exceptional mechanical properties of certain fibers has inspired the use of silk in numerous technical and medical applications. In recent years, computational modeling has clarified the relationship between the molecular architecture and emergent properties of silk fibers and has demonstrated predictive power in studies on novel biomaterials. Here, we review advances in modeling the structure and properties of natural and synthetic silk-based materials, from early structural studies of silkworm cocoon fibers to cutting-edge atomistic simulations of spider silk nanofibrils and the recent use of machine learning models. We explore applications of modeling across length scales: from quantum mechanical studies on model peptides, to atomistic and coarse-grained molecular dynamics simulations of silk proteins, to finite element analysis of spider webs. As computational power and algorithmic efficiency continue to advance, we expect multiscale modeling to become an indispensable tool for understanding nature's most impressive fibers and developing bioinspired functional materials.

One of the key strategies for tissue engineering is to design multifunctional bioinks that balance printability with cytocompatibility. Here, we describe fibrillar hydrogels produced by Schiff base formation between B-type gelatin and oxidized sodium alginate, followed by the incorporation of type I collagen, yielding a new gel (MyoColl). The resulting hydrogel exhibits a temperature- and mass-ratio-dependent sol-gel transition, showing variability of hydrogel properties depending on the component ratio. MyoColl composition provides a convenient platform for biofabrication in terms of shear thinning, yielding, Young's modulus, and shape accuracy. Metabolic activity tests and fluorescent microscopy of 2D hydrogel-based mouse C2C12 myoblast cell culture show significant cytocompatibility of the developed carriers. In addition, primary signs of cell mechanotransduction and myofilament formation of 3D printed MyoColl-based cell cultures were detected and described. Due to these promising results, the described hydrogel composition has shown itself as a convenient platform for muscle tissue engineering.

Poly(β-amino ester) (PBAE) nanoparticles (NPs) show great promise for nonviral gene delivery. Recent studies suggest branched PBAEs (BPBAEs) offer advantages over linear counterparts, but the effect of polymer structure has not been well investigated across many chemical constituents. Here, a library of BPBAEs was synthesized with tri- and tetrafunctional branching. These polymers self-assemble with DNA to form highly cationic, monodisperse NPs with notably small size (∼50 nm). Optimal transfection occurred with polymer structures that featured moderate PBAE branching, enabling complete DNA encapsulation, rapid NP uptake, and robust expression at low DNA doses and polymer amounts. Optimized NPs enabled efficient DNA delivery to diverse cell types in vitro while maintaining high cellular viability, demonstrating significant improvements over a well-performing linear PBAE counterpart. BPBAEs also facilitated efficient mRNA and siRNA delivery, highlighting the versatility of these structures and demonstrating the broad utility of BPBAE NPs as vectors for nucleic acid delivery.

The interaction of the surfactant-like peptide (SLP) R₃L₁₂ bearing three cationic arginine residues with model liposomes is investigated in aqueous solution at various pH values, under conditions for which the SLP self-assembles into nanotubes. The structure of liposomes of model anionic lipid DPPG [1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol)], or zwitterionic lipid DPPE [1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine] is probed using small-angle X-ray scattering and cryogenic-transmission electron microscopy. The unilamellar vesicles of DPPG are significantly restructured in the presence of R₃L₁₂, especially at low pH, and multilamellar vesicles of DPPE are also restructured under these conditions. The SLP promotes the release of cargo encapsulated in the vesicles as probed by calcein fluorescence, with notably higher release for anionic DPPG vesicles. Laurdan fluorescence experiments to probe membrane fluidity (lipid chain ordering) show that R₃L₁₂ destabilizes the lipid gel phase, especially for anionic DPPG. This model nanotube-forming SLP has promise as a pH-sensitive release system for vesicle-encapsulated cargo.

Nanocomposites composed of the cationic polypeptide ε-poly-l-lysine (ε-PL) and natural sodium montmorillonite (MMT) were prepared and evaluated. These MMT/ε-PL composites formed highly ordered nanostructures resembling natural nacreous layers by a simple process. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) analyses confirmed that a small amount of ε-PL remarkably enhanced the MMT orientation in the composites. This MMT orientation-enhancing effect of ε-PL was more pronounced than that of poly(vinyl alcohol) (PVA), which is one of the most popular ingredients of MMT-based composites. The orientation enhancement provided by ε-PL was primarily driven by ionic interactions and responsible for high mechanical properties at low polymer content. This remarkable reinforcing effect of ε-PL on MMT at a low polymer content will help to develop high-performance and sustainable nacreous composites. In addition, it improves our understanding of the reinforcing mechanism of natural nacre, which exhibits excellent mechanical properties even with relatively small amounts of organic component.

Moisture loss, infection, and severe inflammatory reactions are the primary factors affecting burn wound healing and leading to scar formation. Herein, we developed a quercetin-loaded polysaccharide-based injectable hydrogel (named PECE). The PECE consists of oxidized sodium alginate (OAlg) coupled with chitosan (CS) via Schiff bases and electrostatic interactions, while Que is incorporated via hydrogen bonding. Benefiting from the hydroxyl and carboxyl groups, PECE features distinguished moisturizing ability. Additionally, the sustained release of Que imparts remarkable antibacterial activity against Escherichia coli and Staphylococcus aureus. Likewise, PECE demonstrates favorable in vitro anti-inflammatory capacity as released Que significantly downregulates pro-inflammatory factors (IL-6 and TNF-α) secreted by RAW 264.7 macrophages. More importantly, in a rat model of deep second-degree burn wounds, PECE effectively inhibits wound infection, reduces inflammation, and promotes angiogenesis and collagen deposition, ultimately minimizing scar formation. Overall, this work presents a promising strategy for scarless healing of burn wounds.

This study sought to explore the rheological and tribological properties of fucoidan-xanthan gum (XG) mixtures at different fucoidan concentrations. A conformational transition of XG from disordered to ordered forms was observed with an increasing fucoidan concentration, as determined by intrinsic viscosity measurements and Fourier transform infrared analysis. All mixtures exhibited non-Newtonian flow behavior with the yield stress. The mixture sample with 0.5% fucoidan displayed higher apparent viscosity at 100 s^-1, yield stress, and viscoelastic moduli values than XG alone, suggesting viscoelastic synergism between the two biopolymers. However, these values exhibited a decreasing trend with higher fucoidan concentrations (0.5-2.0%), indicating a nullification of synergism. While XG alone exhibited antithixotropic behavior, fucoidan-XG mixtures showed thixotropic behavior, most pronounced at 1.0% fucoidan. A decreasing trend was observed in the maximum friction coefficient as the fucoidan concentration increased, indicating better lubricant properties. Collectively, our findings may enable widespread adoption and application of fucoidan in various industries.

Biomedical polymers play a key role in preventing, diagnosing, and treating diseases, showcasing a wide range of applications. Their unique advantages, such as rich source, good biocompatibility, and excellent modifiability, make them ideal biomaterials for drug delivery, biomedical imaging, and tissue engineering. However, conventional biomedical polymers suffer from poor degradation in vivo, increasing the risks of bioaccumulation and potential toxicity. To address these issues, degradable biomedical polymers can serve as an alternative strategy in biomedicine. Degradable biomedical polymers can efficiently relieve bioaccumulation in vivo and effectively reduce patient burden in disease management. This review comprehensively introduces the classification and properties of biomedical polymers and the recent research progress of degradable biomedical polymers in various diseases. Through an in-depth analysis of their classification, properties, and applications, we aim to provide strong guidance for promoting basic research and clinical translation of degradable biomedical polymers.

The controllability and specificity of peptides make them ideal for targeting therapeutic delivery systems and as therapeutic agents that interfere with the essential functions of pathogens and tumors. Peptides can also mimic natural protein structures or parts thereof, agonize receptors, and be conjugated to other molecules that will self-assemble. In this short Review, we discuss research from the last ten years into peptide use in three arenas: the treatment of cancer, the treatment of pathogens, and the targeting of specific organs and organelles. These studies demonstrate the successful application of targeting and therapeutic peptides in vitro and in vivo and show the promising range of applications peptides can have going forward.

The efficacy of affinity-based treatments for cancer and other diseases is often limited by poor distribution throughout the targeted tissue. Although lower-affinity antibodies will penetrate more uniformly, these often reach lower concentrations because of their rapid clearance from the tissue. To increase retention and improve distribution, we created low-affinity photocrosslinkable affibodies that can diffuse into dense tumor matrices with limited tumor barrier formation and then be photocrosslinked in place to cell receptors to increase retention. In testing with 3D tumor spheroids, the addition of a 50 nM photocrosslinkable affibody showed a similar level of accumulation at the edges of the spheroid but a higher level near the middle of the spheroid than the wild-type (non-photocrosslinkable) affibody. These results show that target affinity affects protein transport in tumor microenvironments and that covalently cross-linking the ligands to cells may improve both their transport and retention.