Biomacromolecules最新文献

Androgenetic alopecia (AGA) is the most common type of hair loss. Its successful treatment depends on effective transdermal drug delivery strategies. In this study, we introduce a novel method utilizing a controlled rigidity nanolipogel (NLG) for the local delivery of fucosterol in the treatment of AGA. The NLG is formed by an identical lipid bilayer encapsulating an alginate core, with rigidity regulated by the degree of sodium alginate (SA) cross-linking. Young's moduli obtained by AFM were 2.91 ± 0.41, 61.5 ± 1.6, and 84.9 ± 1.1 MPa for the soft NLP, moderately rigid NLG-2.5, and most rigid NLG-10. In vitro skin permeation study showed that compared with the NLP and NLG-10, NLG-2.5 had the best transdermal permeability and hair follicle-targeting properties. Moreover, moderately rigid NLG-2.5 exhibited the best ability to inhibit inflammation and androgen pathways and promote angiogenesis, thereby restoring hair growth in AGA model mice. This strategy provides valuable insights for the treatment of AGA.

Soilless cultivation relies on hydrogel matrices for water and nutrient management, but conventional hydrogels lose performance at low temperature and show unstable sustained release. Here this study develops an antifreeze sustained-release hydrogel (P-GTCH) that integrates l-proline (L-P) with a humic-acid-modified cellulose nanocrystal nanocomposite (CNCs-HA) for nanoenabled controlled release. L-P suppresses ice nucleation via hydrogen bonding, while CNCs-HA boosts HA loading and enables controlled transport within the cross-linked network. HA shows slow, continuous release governed by Fickian diffusion, achieving 96.7% cumulative release over 12 days at 0 °C and mitigating poor fertilizer release in cold environments. P-GTCH provides mechanical support for plant roots, and the synergistic effects of L-P and HA maintain lettuce germination above 86% at 0 °C while promoting root growth. This biobased, biodegradable platform is scalable for low-temperature soilless cultivation.

Enzymes such as oxidases are sustainable tools for hydrogel synthesis, but complex competing reactions have limited the mechanistic understanding and biomedical applications of these materials. Guided by molecular docking and MM-GBSA calculations, we identified two artificial substrates, desaminotyrosine (DAT) and desaminotyrosyltyrosine (DATT), that were experimentally more efficiently converted by mushroom tyrosinase (mTyr) than the natural substrate tyrosine. These substrates were used to synthesize hydrogels from DAT/DATT-functionalized star-shaped oligoethylene glycol (sOEG). Model reactions elucidated the chemical nature and functionality of the hydrogel netpoints. Material properties were systematically investigated depending on sOEG molecular weight (5, 10, 20 kDa), substrate type, and mTyr concentration. Functional mesh sizes and controlled release functions were investigated with fluorescent dextrans (4-500 kDa) and heparin. Cell culture studies with L929 fibroblasts and THP-1 monocytes suggested inertness of the material. These findings provide fundamental insight into mTyr-catalyzed hydrogel formation and support further exploration for in situ hydrogel synthesis.

Conventional gelatin-based hydrogel wound dressings suffer from weak mechanical properties, poor temperature stability, and slow wound healing, limiting their practical application. Herein, a novel multifunctional gelatin-based eutectogel dressing (PGEWD) was developed via a multicross-linked network constructed from porcine skin gelatin (PG), ε-polylysine (EPL), waterborne polyurethane (WPU), and deep eutectic solvent (DES, choline chloride-glycerol). DES induced PG molecular chain rearrangement to form a dense triple-helix structure. With the optimal formulation of 10% EPL, 0.3% WPU, and 10 min DES immersion, the PGE_0.1W_0.3D₁₀ composite exhibited high tensile strength (290 kPa), intrinsic conductivity (0.798 mS/cm), wide thermal tolerance (-20 to 60 °C), and ∼100% antibacterial activity. Combined with electrical stimulation (ES), it accelerated wound healing with ∼94.47% closure rate in 14 days. This study provides a versatile strategy for designing multifunctional gelatin-based wound dressings with significant potential in wound regeneration.

Liquid-liquid phase separation (LLPS) is involved in both the self-assembly of vital cellular organelles and the disease-associated protein misfolding, where LLPS precedes a liquid-solid phase transition (LSPT) leading to amyloid aggregates. Chimeric ACC_1-13K_n peptides are insightful models to study coupled LLPS/LSPT processes triggered by ATP-binding. Here, we investigated the impact of macromolecular crowding on the selection of the aggregation pathway in the ACC_1-13K₈-ATP system. While it has been previously shown that peptides with relatively short oligolysine segments (K₁₆ and shorter) skip the LLPS stage on their pathway to amyloid fibrils, we show here that concentrated polyethylene glycol (PEG), mimicking intracellular crowding conditions, induces prior formation of liquid droplets that subsequently facilitate fibril formation. The influence of PEG contrasts with the behavior of other types of macromolecular crowding agents, Dextran and Ficoll, which accelerate aggregation without a detectable LLPS phase, and that of serum albumin, which prolongs the nucleation phase. In the presence of PEG-induced macromolecular crowding, the fibrillization in the ACC_1-13K₈-ATP system appears to reach a maximal rate limited by diffusion coupled to the conformational dynamics of the polypeptide chains within the droplets. Importantly, the ACC_1-13K₈-ATP fibrils formed in the presence of PEG are distinct from those of the ACC_1-13K₈-ATP amyloid formed in the absence of crowding in terms of their infrared characteristics, morphological features, and overall stability. Our findings suggest that macromolecular crowding can switch between kinetically and thermodynamically favored amyloid polymorphs and that the chemical properties of the crowding agents are key factors in their impact on protein aggregation processes. The results are discussed in the context of the mechanisms of LLPS-dependent protein misfolding and amyloid formation.

Multifunctional textiles integrating antimicrobial and thermal-regulatory properties are urgently needed for wound care and personal protection. Here, we developed antibacterial and thermoregulatory Lyocell fibers through covalently grafting aloin and integrating graphene oxide (GO) with phase-change microcapsules (PCMs). The optimal Functional fiber 2 (3% aloin, 4 mg/mL postimmersion aloin, 0.75% GO, and 30% PCMs) exhibited a cylindrical morphology with protrusions and microvoids, and demonstrated 27.61 J/g phase change enthalpy, 16.18 cN tensile strength, and 22.24% breaking elongation. Under standardized shake-flask conditions, Functional fiber 2 completely inhibited Staphylococcus aureus and Escherichia coli growth, and antibacterial efficacy remained at 90.21% and 87.81% after 30 washing cycles. In S. aureus-infected rat wounds, the fiber accelerated healing, reduced the wound diameter by approximately 77% via 14-day treatment, prevented bacterial infection/inflammation, and enhanced angiogenesis. Our fibers are promising for manufacturing protective textiles and medical supplies, also showcasing potential in outdoor protection.

Oral hard-soft tissue repair present significant clinical challenges due to the highly dynamic, moist, microbially colonized, and inflammatory nature of the oral environment. Oral wounds from trauma, surgery, or disease cause discomfort and infection risk, demanding effective protection. The development of wet adhesives capable of robust adhesion to integrate oral hard tissues and soft tissues, while enabling localized therapy, remains a significant challenge. In recent years, hydrogels with tunable surface energy and reversible adhesion have demonstrated exceptional wet adhesion through the synergy of physical, chemical, and dissipative interactions, showing great potential to improve therapeutic effect in oral surgical applications. This review comprehensively examines wet adhesion mechanisms of hydrogels and critically analyzes the physical and chemical foundations of current dental adhesives. By integrating surface modification of hydrogels to the unique requirements of oral soft and hard tissue repair, this work aims to develop next-generation materials that overcome clinical translation barriers.

Degradable polyester materials are widely utilized in medicine as resorbable sutures, implantable devices, and drug delivery. These applications require precise and tunable degradation control; predictable number-average molecular weight (M̅_n), narrow polydispersity (Đ), and diverse material properties define polyester utility, which are not easily achieved through well-established synthesis approaches. Ring-opening copolymerization (ROCOP) provides reproducible M̅_n control, narrow Đ, and expands monomer diversity. In this work, poly(cyclohexene succinate) (PCS) and poly(propylene succinate) (PPS) were synthesized through a central composite design of experiments approach, systematically varying anhydride:epoxide ratio, monomer:catalyst ratio, reaction temperature, and reaction time. Reduced synthesis factor-response models explained the significant variation for all characterized properties relevant to degradation control. PCS and PPS readily degraded under base-catalyzed hydrolysis conditions with significantly higher mass loss in PPS materials compared to PCS, highlighting the monomer selection influence in degradation behavior. These findings highlight the potential for ROCOP to generate degradable biomaterials with reproducible material properties for application-specific biomedical use.

Elastin-like polypeptides (ELPs) are self-assembling recombinant biopolymers that can be precisely engineered to display functional targeting ligands. In this study, we developed ELP-based nanoparticles (NPs) displaying the variable domain of the heavy chain of heavy-chain-only antibodies (VHHs) targeting the SARS-CoV-2 spike protein. By tuning VHH selection, multivalency, and surface display density, we created targeted ELP NPs capable of blocking entry of spike-protein-presenting virus-like particles (VLPs) and live viruses, with subnanomolar IC₅₀ values, significantly outperforming the monovalent VHH equivalents. Notably, optimizing multivalency and VHH density unlocked broad virus-neutralizing potency against multiple variants, including Omicron variants resistant against the monovalent VHH equivalents. Confocal imaging further revealed that VHH-ELP NPs formed aggregates with VLPs, enhancing uptake by M1 macrophages, suggesting potential for eliciting vaccinal effects. Overall, this work highlights the versatility of ELP NPs as a tunable antiviral platform and provides design principles for next-generation nanotherapeutics against evolving viral threats.

Cellulose nanofiber (CNF) has been reported to enhance the mechanical and crystallization properties of poly(lactic acid) (PLA); nevertheless, its role in PLA chemical recycling via pyrolysis remains unexplored. This study revealed that PLA incorporated with 3 wt % CNF (PLA/CNF3) exhibited a marked reduction in its thermal depolymerization activation energy to 152 kJ/mol, compared to 169 kJ/mol of neat PLA, indicating that CNF facilitated thermal depolymerization of PLA. Further investigation by pyrolysis-GC/MS showed that pyrolyzates of PLA/CNF3 contained mainly lactide (≈90%) in contrast to only 69% lactide in that of neat PLA, confirming that the addition of CNF catalyzed the thermal depolymerization of PLA into lactide. The water molecule released from the CNF accelerates PLA hydrolysis, forming -COOH-terminated oligomers in situ, which then intensify the autocatalytic degradation. This finding highlights another important role of CNF in PLA as a green catalyst for thermal depolymerization, advancing PLA chemical recycling for plastic circularity.