Parkinson's disease (PD) is difficult to treat clinically and lacks an effective treatment. The aim of this study was to synthesize and characterize butyrate-modified hyaluronic acid (HA-But), validate its therapeutic efficacy, and elucidate its mechanisms of action in PD. Behavioral tests, including the open field test, Y-maze, and elevated plus maze test, demonstrated that HA-But significantly alleviated motor dysfunction in PD mice. ELISA results indicated a marked reduction in pro-inflammatory cytokine levels following the HA-But treatment. In addition, immunohistochemistry, immunofluorescence, and Western blot analyses revealed that HA-But improved dopaminergic neuron survival and reduced α-synuclein aggregation. Furthermore, HA-But activated PINK1/Parkin-mediated mitophagy, modulated gut microbiota composition, and increased short-chain fatty acid (SCFA) levels, especially butyric acid. Combining HA-But with gastrodin further improved the PD symptoms in mice. These findings suggested the potential of HA-But as a novel approach for PD treatment.

Similar to cellulose nanocrystals (CNCs), rod-shaped chitin nanocrystals (ChNCs) form liquid-crystalline cholesteric (chiral nematic) suspensions in water. In this paper, we report how the biological source from which the ChNCs were obtained influences the properties of their liquid-crystalline suspensions, specifically their phase separation diagram and helical pitch. We isolated ChNCs under the same acid hydrolysis conditions from chitin of various biological sources, i.e., snow crab, shrimp, Antarctic krill, squid, black soldier fly pupae, and oyster mushroom, and investigated their geometrical dimensions and surface charges as well as their liquid-crystalline suspension. Our key result is that the biological source has indeed a major impact on the length and the aspect ratio of the ChNCs, which in turn significantly influences the stability range and the helical pitch of their chiral-nematic aqueous suspensions. Remarkably, a much smaller helical pitch was observed for ChNCs derived from oyster mushroom. Overall, it has become clear that the biological origin of ChNCs indeed matters for their properties and their potential applications.

Biomimetic materials are of significant interest in applications such as soft tissue repair, with their ability to replicate morphology and properties of native tissue. This study reports a novel thermoplastic polyurethane (TPU) synthesized with an amino acid-based diisocyanate hard segment. The effects of hard segment percentage on the mechanical, thermal, and hydrophilic properties were assessed. The optimal TPU shows a Young's modulus of 0.19 MPa, a tensile strength of 0.61 MPa, and an elongation at break of 2375%. Incorporating a novel functionalized clay in this TPU gives excellent antibacterial properties, demonstrating efficacy against both Gram-positive and Gram-negative bacterial strains. The addition of this clay also significantly enhances the mechanical properties of the TPU, with Young's modulus increasing by up to 26 times with 3 wt % clay. The TPU was spun into fibers, creating a fibrous scaffold mimicking the architecture of some soft tissues. The TPU fibers exhibit a considerably higher tensile strength compared to bulk TPU while maintaining a high elongation at break. These TPUs and TPU-clay nanocomposites may find potential applications in soft tissue scaffolds or patches with antibacterial or anti-inflammatory behavior, for example, for the repair of gastrointestinal tissue that may be exposed to harmful bacteria.

Understanding the long-term stability of cellulose nanofibers is critical for their practical application in advanced functional materials. In this study, we investigated the aging behavior of phosphorylated cellulose nanofibers (PCNFs) sheets under moist-heat accelerated aging conditions (80 °C, 65% relative humidity (RH)) for up to 42 days. PCNFs with different phosphate group densities were prepared by controlling the phosphorylation time, and their chemical and morphological changes were systematically analyzed. Liquid-staP NMR revealed a progressive transformation of surface phosphate esters into inorganic phosphate salts during aging. This dephosphorylation was thought to lead to a decrease in the pH within the sheets, which in turn promoted hydrolysis of the cellulose backbone. The resulting degradation manifested as decreases in the degree of polymerization (DP) and fibril length, particularly in PCNFs with higher surface charge. Conversely, the lateral crystallite size of the cellulose increased. These findings provide insights into PCNF aging and highlight the importance of controlling the initial phosphate ester structure and environmental conditions to increase the stability of PCNF-based materials in practical applications.

Targeted drug delivery systems that are stimuli-responsive offer great potential for enhancing the therapeutic activity of drugs, decreasing off-target effects, and improving bioavailability. This proof-of-concept study introduces an amphiphilic drug delivery system (DDS) capable of loading hydrophobic cargo. Elevated glutathione (GSH) levels, characteristic of certain types of cancer cells' microenvironment, degrade the nanostructures and release the cargo. Linear polyglycerol sulfate (LPGS), known for its excellent biocompatibility, is combined with lipoic acid (LA). LA facilitates the formation of cross-linked nanosheet amphiphiles sensitive to reductive conditions. Morphological changes are observed by scanning electron microscopy (SEM), cryogenic transmission electron microscopy (Cryo-TEM), and cryogenic electron tomography (Cryo-ET) upon UV irradiation (ν), creating a stable aggregate for loading hydrophobic cargo and assembling into sheets at elevated concentrations. The resulting material displays controlled release of model dyes under increased levels of GSH, tunable by the polymer size and LPGS:LA acid ratios. This behavior enhances targeted therapy and reduced off-target effects. Further loading with paclitaxel and subsequent release, together with assays, demonstrates the system's compatibility with an anticancer drug.

We report the biological evaluation of bis-MPA dendrimers terminated with either cysteamine (CYS) or 2-(dimethylamino)ethanethiol (DA) groups for siRNA transfection. The results show that aggregation phenomena are critical to the biological performance of these constructs. Confocal and 2D microscopy demonstrated that only the G3-CYS dendrimer transported siRNA into cells. Accordingly, G3-CYS-mediated siRNA transfection reduced intracellular levels of the target proteins─p42-MAPK, Rheb, and MGMT─to 15-25% of control levels in a human glioblastoma cell line and mouse astrocytes. G3-CYS transfection efficiency was similar to that of commercial transfectants. However, its self-degradable bis-MPA backbone and tunable peripheral groups render it markedly superior, making it a promising transfection agent and emphasize the critical balance between structural design, biological efficacy, and safety. Despite its efficacy, G3-CYS displayed a narrow therapeutic window with pronounced cytotoxicity above 1 μM. In vivo studies further confirmed dose-dependent systemic toxicity, likely associated with enhanced blood coagulation.

Cellulose-based materials have been widely studied due to their biodegradability and excellent mechanical strength. However, the intrinsic brittleness of cellulose limits its applications. In this study, the bacterial cellulose-chitosan films were prepared by a casting method. The cellulose films with ≤ 30% chitosan exhibited a simultaneous increase in strength and toughness. The slippage of cellulose chains and dense network structure contribute to the improved strength and toughness of the cellulose-chitosan films. Besides, coarse-grained molecular dynamics simulations were performed to investigate the effects of different molecular factors (i.e., chain length, molecular interaction strength, and density) on the mechanical properties of cellulose-chitosan films. These molecular factors exhibited opposite effects on the tensile strength and strain at break. In particular, modifying the density of cellulose-chitosan films could simultaneously improve the strength and toughness significantly without sacrificing the elastic modulus. The findings provide physical insights into the strengthening and toughening effects of the cellulose-chitosan films.

The stabilization of phase change materials (PCMs) in high internal phase emulsions (HIPEs) remains particularly challenging due to their inherent properties, significantly hindering their application in functional materials. Here, we introduce a versatile strategy in which oppositely charged cellulose nanofibrils (CNF) and didodecyl dimethylammonium bromide (DDAB) cooperate to construct PCM-in-water high internal phase Pickering emulsions (HIPPEs). The stabilization mechanism relies on a dual barrier: (i) electrostatic adsorption of CNF/DDAB complexes at the oil-water interface forms a dense and reversible interfacial film; (ii) a percolating CNF network in the continuous phase suppresses droplet migration through steric hindrance and viscoelasticity. Consequently, the emulsions remain stable over 30 days at room temperature, these HIPPEs suit diverse oils (including difficult-to-stabilize liquid paraffin) with up to 92% internal-phase volume, serving as green templates/3D printing inks and expanding the fabrication window for programmable HIPPEs in latent-heat storage and thermal management.

Small-molecule STAT3 inhibitors face numerous challenges in clinical translation, including poor water solubility, rapid systemic clearance, low bioavailability, poor selectivity, and high cytotoxicity. To address these limitations, we conjugated the potent STAT3 inhibitor-LLL12 to generate six (G6) hydroxyl-terminated (poly(amidoamine)) PAMAM dendrimers using pH-sensitive linkers: sulfonyl carbamate (carbamate), sulfonyl carbamoyl (amide), and hydrazone for intracellular drug delivery. Conjugation greatly enhanced LLL12 solubility (up to 10 mg/mL) and reduced cytotoxicity without altering dendrimer size or surface charge. All three G6-LLL12 conjugates remained stable under neutral pH but exhibited sustained, pH-dependent drug release correlating with potency and cytotoxicity. Notably, hydrazone-linked conjugate showed an IC = 0.42 ± 0.035 μg/mL, comparable to free LLL12 (IC = 0.31 ± 0.05 μg/mL) and superior to amide- and carbamate-linked conjugates. In bone marrow-derived immune suppressive myeloid cells, hydrazone-based G6-LLL12 effectively reduciii-derrive, hydrazone-based G6-LLL12 effectively reduced monocytic myeloid-derived suppressor cell expansion and promoted antigen-presenting cell maturation, highlighting a promising pH-responsive delivery system that enhances solubility and safety while retaining potency.

Their minimally invasive application and adaptability to irregular wounds make injectable hydrogel adhesives attractive for hemostasis and wound closure in surgical and emergency settings. However, current systems suffer from low mechanical strength, weak adhesion, and complex procedures. Here, we propose ADP-PPZ, a single-component, thermoresponsive hydrogel adhesive based on poly(organophosphazene) functionalized with succinimidyl carbonate (SC) groups. ADP-PPZ is readily injectable in its sol state at room temperature (RT), and rapidly gels at body temperature hydrophobic interactions without external stimuli. Simultaneously, SC groups react with tissue amines, achieving adhesion. The hydrogel exhibits fast gelation (5.5 s), sufficient mechanical strength, effective adhesion (23 kPa), low swelling, biocompatibility, and biodegradability. Moreover compared to PEG-based adhesives, ADP-PPZ demonstrated superior performance, exhibiting rapid hemostasis, stable tissue sealing, re-epithelialization, and collagen remodeling. Collectively, these results establish ADP-PPZ as a novel design strategy that enables independent gelation and tissue adhesion within a single-component hydrogel, offering potential for hemostasis and regenerative applications.

Lipid nanoparticles (LNPs) are the most widely applied nanocarriers for mRNA delivery in clinical use. However, the limited stability and increasingly recognized immunogenicity of PEG-based LNP formulations are potential impediments to the more widespread development of mRNA therapeutics. To address shortcomings in current LNP polymer coatings, we have developed a polymer-lipid conjugate based on the low-fouling sulfoxide polymer poly(2-(methylsulfinyl)ethyl acrylate) (PMSEA). The results show that LNPs formed from the PMSEA-DSPE conjugates with optimized polymer chain length have excellent stability, highly effective shielding, and low immunogenicity, favorable properties for PMSEA-DSPE to be incorporated as a component of mRNA nanocarriers. mRNA-LNP formulations were prepared with PMSEA-DSPE as an alternative to the PEGylated formulations. The stability, behavior, and transfection efficiency of the mRNA nanocarriers were evaluated, with PMSEA providing superior transfection efficiency compared with the PEG equivalents. This work demonstrates the potential of PMSEA mRNA-LNPs for further development as therapeutic delivery vehicles.

Phosphorylation is considered to play a role in many of the functional properties of silk proteins, affecting their solubility, environmental adaptability, adhesion, and biocompatibility. However, investigating these effects has been hampered by the difficulty of isolating phosphorylated proteins from natural sources and the limitations of the current phosphorylation techniques. Here, we present a novel phosphorylation strategy for recombinant silk proteins in , utilizing an engineered SpyCatcher/SpyTag system to induce proximity between the target protein and kinase. This scaffolding approach enhances kinase specificity and minimizes off-target effects, increasing the phosphorylation efficiency while preserving cell viability. We demonstrate the applicability of this system to both dragline and aggregate spider silks. Furthermore, we show that polyphosphorylation enhanced the adhesive properties of silk proteins. This modular and tunable strategy provides a powerful platform for producing polyphosphorylated fibrous proteins, offering broad implications for biomaterial design and functional protein engineering.

Hydroxypropyl cellulose (HPC) is a biobased, biodegradable, and water-soluble material that is used as an emulsifier, thickener, and stabilizer in aqueous formulations. Its solid-state properties render HPC also attractive for water-soluble sanitary products, packaging, and biomedical applications. While HPC films and coatings are well-known, HPC fibers have hardly been investigated, arguably, due to the lack of methods to spin HPC fibers. Here, we show that fibers can readily be produced by wet spinning aqueous HPC solutions into an aqueous CaCl coagulation bath. This process induces significant alignment of HPC chains under shear forces, resulting in fibers with considerably higher stiffness (Young's modulus = 1.3 GPa) and tensile strength (36 MPa) than solution-cast HPC films (Young's modulus = 0.7 GPa, tensile strength = 19 MPa). The HPC fibers retain their mechanical integrity upon conditioning at 60% relative humidity, although stiffness is considerably reduced. Wet spinning is readily scalable and affords stiff and strong fibers that represent a promising alternative to woven and nonwoven synthetic fibers.

We introduce generation-specific thermoresponsive dendrons that undergo reversible, temperature-triggered conformational changes with an "umbrella-like" conformation. Built from sequence-defined polymer segments via chemoselective iterative coupling, where we could independently control the stimulus response within each generational layer to obviate cooperative behavior. This noncooperative LCST transition enables selective collapse or expansion within individual generational layers. When grafted to gold nanoparticles with distinct thermal transition states, they form tunable umbrella-like architectures that control grafting density, footprint, and peripheral chain coverage. This structural modulation directly impacts the catalytic activity for the reduction of methylene blue in water, where reaction rates are governed by the balance between accessible gold active sites and diffusion through the polymer corona. These dendritic surface-grafted architectures maintained exceptional colloidal stability while preserving high catalytic accessibility, establishing a versatile platform for stimuli-responsive nanomaterials in catalysis, sensing, and biomolecular recognition.

Food packaging is critical to prevent food waste, but most of the packaging used today is not sustainable. Paper-based packaging materials offer a renewable option, but exhibit poor resistance to common permeants such as oxygen, grease, and water vapor. In this work, a complex coacervate coating is prepared from two waste biopolymers, gelatin and DNA, and applied to kraft paper to substantially improve its barrier properties. Thermally curing the coating after deposition decreases the water vapor transmission rate and oxygen transmission rate by 83 and 99%, respectively, relative to uncoated paper. This work represents one of the best fully biobased barrier coatings reported for paper and is a promising option for sustainable food packaging.

In this study, we developed multifunctional nanoparticles based on polyamidoamine (PAMAM) dendrimers functionalized with caffeic acid (CA) and poly(ethylene glycol) maleimide (PEGM) for the topical delivery of hydrophobic antiglaucoma drugs brimonidine (BM) and betaxolol (BX). The PAMAM-CA and PAMAM-CA-PEGM conjugates exhibited antioxidant and iron-chelating activities in a dose-dependent manner. BM- and BX-loaded dendrimer nanoparticles produced using a multi-inlet vortex mixer showed uniform spherical morphology (∼80 nm by TEM) and hydrated sizes of ∼135-144 nm by DLS. Both nanoformulations demonstrated high cytocompatibility with human corneal epithelial cells and were nonirritant in the HET-CAM assay, with PEGM further improving cytocompatibility. Drug release was sustained for 8 h. corneal permeation studies revealed significantly enhanced drug transport, with PAMAM-CA and PAMAM-CA-PEGM nanoparticles achieving approximately 2- and 3-fold higher permeation, respectively, compared to commercial formulations. Conjugation of CA within our formulations effectively promoted the removal of ferric ions from the surrounding environment. Both PAMAM-CA and PAMAM-CA-PEGM nanoparticles exhibited concentration-dependent antioxidant activity comparable to that of CA. These findings suggest the potential of this multifunctional dendrimer-based nanoparticle system as an innovative strategy for glaucoma medication.

Postoperative atrial fibrillation (POAF) is a common surgical complication linked to atrial inflammation and oxidative stress. Here, we developed a strategy integrating chemical modification of therapeutics, poly(lactic--glycolic acid) (PLGA)-mediated sustained kinetics, and hydrogel-enabled spatial targeting to achieve continuous, local drug delivery to the atrial region. Andrographolide was modified with phenylboronic acid (PBAn) to change its solubility and enhance drug-loading capacity in PLGA microspheres, while enabling responsive drug release. We further constructed an injectable bioadhesive hydrogel via mixing of a copolymer and O-carboxymethyl chitosan, which adhered to cardiac tissue. In vitro, PBAn demonstrated ROS-responsive release, along with anti-inflammatory and antioxidant effects on RAW264.7 and HL-1 cells. In a rat pericarditis model, this localized system significantly reduced atrial inflammation and oxidative stress, promoted anti-inflammatory M2 macrophage polarization, enhanced electrical stability, and markedly decreased POAF susceptibility.

Heparin is a critical anticoagulant, yet its purification remains challenging. Most commercial adsorbents are derived from petroleum-based polymers, which may introduce microplastics into the human bloodstream during medical use, posing a potential health risk. Herein, we report a regenerated positively charged cellulose nanofibril (PCCNF)-based hydrogel as a green and efficient alternative for selective heparin extraction. With quaternary ammonium modification, PCCNFs capture ∼88% heparin within 1 min, which outperforms commercial Amberlite IRA-900. We then produce regenerated cationic cellulose (cCell) hydrogels through an ionic liquid (IL) dissolution and regeneration process from PCCNFs, and we demonstrate their high selectivity toward heparin even in the presence of protein contaminants and their excellent reusability over multiple cycles. Finally, the regenerated cCell hydrogels are fabricated into monodispersed spheres via electrospraying for column-based operations, and efficient heparin extraction is verified. This work highlights the potential of regenerated cellulose-based hydrogels as scalable, sustainable substitutes for conventional plastic adsorbents in the recovery of heparin and other polyelectrolytes.

Reactive oxygen species (ROS) are vital but harmful in excess, and numerous small molecule antioxidants (e.g., polyphenols) can help to maintain an optimal ROS balance. Considering factors like biocompatibility, it is more commonly preferred to transform these natural antioxidants into nanoscavengers through a macromolecular engineering strategy. However, conventional macromolecular antioxidants typically exhibit decreased scavenging capacity compared to monomers due to steric hindrance and oxidation during the polymerization. To tackle this issue, we developed robust degradable macromolecular nanoscavengers by polymerizing dopamine and 4-formylphenylboronic acid. Featuring boronate-catechol linkages, these nanoscavengers boost antioxidation by degrading and exposing functional groups in acidic or ROS environments, showing greater capacity than monomers and polydopamine nanoparticles. Those nanoscavengers were subsequently employed to temporomandibular joint osteoarthritis, suppressing both oxidative stress and inflammation to effectively alleviate the disease progression. This study offers new insights into the design and synthesis of degradable macromolecular antioxidants for inflammation treatment.

Lignocellulosic materials present the largest source of biomass for biotechnology and green energy. This study aimed at better understanding the cell wall disintegration mechanisms relevant for the biochemical conversion of biomass to carbohydrates. Herein, we examined nanoscale changes in cell wall structure and composition upon industrially relevant chemical and enzymatic treatments to achieve the desired level of breakdown. One treatment involved hydrogen peroxide and acetic acid to remove lignin. Another modification used the cellulase enzyme for cell wall degradation. Band excitation contact resonance atomic force microscopy was used to visualize and mechanically characterize cell wall layers. After cellulase treatments, we detected microcracks across the cell wall. Wet-chemical, Fourier-transform infrared and Raman spectroscopic analyses confirmed the removal of lignin and extractives through acid bleaching, while the enzymatic treatment minimally affected the biopolymer composition. Delignification resulted in cell wall delamination and reduced stiffness. X-ray diffraction revealed changes in cellulose structure and crystallinity.

The advancement of personalized antiaging therapies demands the convergence of biomaterial innovation and precision fabrication technologies. Here, we present the development of a dual-cross-linked collagen-based bioink, integrating methacrylated collagen (CMA) and 1,4-butanediol diglycidyl ether (BDDE), tailored for DLP-based bioprinting. BDDE functions as a chemical cross-linker by forming stable ether bonds with hydroxyl groups on the collagen backbone, thereby reinforcing the structural integrity of the matrix. Subsequent photo-cross-linking of CMA generates an interpenetrating network that imparts superior enhancements to mechanical resilience, proteolytic endurance, and structural robustness. Bioink supports high-resolution cell-laden printing and enables the fabrication of geometrically complex, high-fidelity constructs. Moreover, the incorporation of bioactive retinol (VA) allows for the fabrication of functionalized hydrogel facial patches with targeted antiaging activity. studies were performed employing a D-galactose-induced aging model demonstrated significant improvements in dermal density, transepidermal water loss (TEWL), and antioxidant capacity. The CMA/BDDE bioink thus offers a versatile, clinically relevant platform for next-generation regenerative esthetics and personalized dermatological interventions.