Despite the rapid development of cellulose-stabilized oil-in-water emulsions, water-in-oil high internal phase emulsions (HIPEs) remain underexplored, limiting the structural diversity of Pickering-templated porous mater...Despite the rapid development of cellulose-stabilized oil-in-water emulsions, water-in-oil high internal phase emulsions (HIPEs) remain underexplored, limiting the structural diversity of Pickering-templated porous materials. Here, we introduce TEMPO-oxidized cellulose nanofibrils noncovalently modified with dialkyl-chain cationic surfactants as highly effective stabilizers for water-in-oil HIPEs (>95% internal phase), enabling versatile designs for porous polymers and aerogels. Crucially, adjusting reaction temperature controls pore connectivity in porous polymers, eliminating complex formulation adjustments. Furthermore, this strategy enables the one-pot production of near-superhydrophobic (contact angle ∼147°), thermally insulating (26.7 mW/(m·K)) aerogels with customizable three-dimensional architectures and efficient oil-water separation, without hydrophobic post-treatment. These properties are fine-tuned by modifying the template, and functional additives are easily incorporated to improve flame retardancy and thermal stability. This study presents a novel strategy to tailor porous polymer structures via temperature regulation and pioneers the one-pot fabrication of hydrophobic, thermally insulating cellulose-based aerogels using water-in-oil emulsions.
The differences in the phospholipid profile between bacterial and mammalian membranes present a promising direction for designing antimicrobial peptides (AMPs). A key challenge, however, is engineering AMPs with a high a...The differences in the phospholipid profile between bacterial and mammalian membranes present a promising direction for designing antimicrobial peptides (AMPs). A key challenge, however, is engineering AMPs with a high affinity for bacterial anionic phospholipid (phosphatidylglycerol, PG) while minimizing off-target interactions with mammalian phosphatidylserine (PS). Herein, we report a multiarmed radially amphiphilic AMP (maRAP) design that enhances PG recognition, exhibiting potent antibacterial activity and exceptional antibacterial selectivity. Compared to the single-arm RAP (1aRAP), maRAPs exhibited superior affinity for PG, yet they exhibited negligible binding to PS. They also demonstrated significantly enhanced bactericidal efficacy and selectivity over 1aRAP in complex physiological environments. In the murine bladder-infection model, maRAPs more effectively reduced the bacterial load and attenuated infection-induced tissue damage, as demonstrated by an intact urothelial lining and minimal lamina propria edema at the infection site. This work presents the multiarm strategy as an effective approach for advanced AMP development.
Protein-based hydrogels have been constrained by modest mechanics and limited responsiveness. In this study, a light-triggered, disulfide-cross-linked hydrogel based on poly(γ-glutamic acid) (γ-PGA) was established by in...Protein-based hydrogels have been constrained by modest mechanics and limited responsiveness. In this study, a light-triggered, disulfide-cross-linked hydrogel based on poly(γ-glutamic acid) (γ-PGA) was established by integrating thiolated γ-PGA and α-lipoic acid (LA)-grafted γ-PGA under 405 nm irradiation. Dynamic disulfide chemistry enabled rapid gelation at a critical concentration of ≥7%, with complete gelation at a polymer concentration of 8%, a storage modulus of approximately 100 Pa, and gelation time below 60 s at 0.25% LAP. The hydrogel adhered to diverse substrates, underwent redox-triggered disassembly within 5 min in the presence of β-mercaptoethanol (βME), and maintained integrity in simulated gastric fluid (pH = 2) with about 18% mass loss after 2 h. Broad-spectrum antioxidant activity was observed, including disappearance of the 1,1-diphenyl-2-picryl-hydrazyl peak at 517 nm at 4 mg/mL and approximately 80% scavenging of hydroxyl radicals. Cytocompatibility was supported up to 640 μg/mL. In lipopolysaccharide (LPS)-stimulated macrophages, pretreatment reduced reactive oxygen species (ROS) and nitric oxide (NO), preserved mitochondrial membrane potential (ΔΨm), and shifted gene expression toward an anti-inflammatory profile. These findings indicated that dynamic disulfide chemistry endowed the γ-PGA platform with programmable gelation, reversible adhesion, gastric stability, and coupled antioxidant and anti-inflammatory activities relevant to food-related oral delivery.
This study introduces a high-performance, fully biodegradable starch-based water-activated paper tape as a sustainable alternative to conventional petroleum-based packaging tapes. The key innovation is a physically cross...This study introduces a high-performance, fully biodegradable starch-based water-activated paper tape as a sustainable alternative to conventional petroleum-based packaging tapes. The key innovation is a physically cross-linked adhesive system utilizing synergistic interactions between waxy cassava starch (WCS) and poly(vinyl alcohol) (PVA), with carboxymethyl cellulose (CMC) incorporated as a network enhancer. This ternary composition forms a robust hydrogen-bonded network that overcomes the typical limitations of starch adhesives, such as inadequate peel strength and poor thermal stability. The resulting tape demonstrates superior performance, achieving a peel strength of 6.3 N/cm and a tack grade of #10 on the steel ball test, markedly exceeding commercially available products, which typically reach 4-5 N/cm and grade #7-8. By combining high mechanical strength, rapid wet-adhesion capability, and complete biodegradability, this work provides a scalable and eco-friendly solution for corrugated packaging, effectively addressing the environmental challenge of persistent plastic waste from single-use applications.
BACKGROUND: The molecular weight of complicated biological macromolecules is typically difficult to determine precisely. As an example, the complicated nature of high viscosity, low solubility, and extremely broad MW dis...BACKGROUND: The molecular weight of complicated biological macromolecules is typically difficult to determine precisely. As an example, the complicated nature of high viscosity, low solubility, and extremely broad MW distribution of polydeoxyribonucleotide (PDRN), which was extracted from salmon sperm cells and possesses a number of physiological activities related to its weight-average molecular weight (MW), subjected it to challenges for accurate MW determination. The commonly used technologies such as mass spectrometry and gel electrophoresis might not work properly for the accurate determination of PDRN MW; thus, it is necessary to develop effective analytical methods to address this challenge. METHODS AND RESULTS: Considering PDRN as a polymer sample, multiangle light scattering (MALS) was employed for analysis. Both size-exclusion chromatography-MALS (SEC-MALS) and asymmetric flow field-flow fractionation-MALS (AF4-MALS) obtained consistent MW results. Notably, AF4-MALS has achieved the preliminary separation and quantification of RNA impurities in PDRN samples. Additionally, considering PDRN as a single-particle sample, the mass photometry was employed as an orthogonal technique for MALS measurement. It is demonstrated that the MW results obtained by the three methods were consistent. CONCLUSION: It is demonstrated that the developed orthogonal methods can get a consistent MW of PDRN, also providing an example of how these methods can provide both "overall" and "single-particle" data that will be useful in accurate weight-average molecular weight determination of complicated biological samples.
Chen H, Qiao Y, Liu J
… +5 more, Bian D, Zhao Y, Fan X, Du J, Zhang S
Biomacromolecules
· 2026 May · PMID 41842712
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Long-term tumor immunotherapy remains challenging due to poor drug retention and immune activation. Here, we proposed a chitosan-based composite hydrogel capable of in situ gelation at physiological temperature to form a...Long-term tumor immunotherapy remains challenging due to poor drug retention and immune activation. Here, we proposed a chitosan-based composite hydrogel capable of in situ gelation at physiological temperature to form a durable depot for sustained and tumor microenvironment (TME)-responsive release. The system integrated indocyanine green (ICG)-loaded gold nanorods within boronic acid-modified mesoporous silica (GSB) and thermoresponsive nanocomposites (ICG@GAN), which were further loaded with β-glycerophosphate (β-GP) and genipin and embedded in a carboxymethyl chitosan matrix. Upon injection, sequential release of β-GP and genipin triggered rapid physical and stable chemical cross-linking, forming a high-strength double-network hydrogel. Gradual leaching of β-GP, along with enzymatic degradation of chitosan, sustained the release of ICG@GAN. In the TME, cleavage of boronate esters triggered the release of ICG and GSB, enabling synergistic photothermal and ROS-mediated tumor cell apoptosis and tumor-associated macrophage repolarization. Meanwhile, chitosan modulated the immune feedback to amplify immune activation and infiltration. This integrated hydrogel platform markedly suppressed tumor growth and metastasis, offering a promising strategy for long-term immunotherapy.
Biobased degradable polyesters have emerged as a promising alternative to mitigate plastic pollution and reduce dependence on petroleum resources. However, the utilization of tricyclic rigid diols derived from biomass re...Biobased degradable polyesters have emerged as a promising alternative to mitigate plastic pollution and reduce dependence on petroleum resources. However, the utilization of tricyclic rigid diols derived from biomass remains limited, which restricts the overall performance of degradable polyesters. In this study, a novel diglycolicaldehyde xylose (DGX) diol containing a rigid tricyclic structure, synthesized from D-xylose and glyoxylic acid hydrate, is reported. Both the single- and multiple-stereoisomer forms of DGX were polymerized with linear diacids of varying carbon chain lengths to produce biobased poly(xylosediethylene alkylenedicarboxylate)s (PXAs) and m-PXAs polyesters. The high rigidity of the single-regioisomer DGX conferred enhanced thermal properties to PXAs, with a 5% weight loss temperature () reaching 372 °C and a glass transition temperature () of up to 93.8 °C. The structural regularity of the PXAs polymer backbone, combined with their higher molecular weights, resulted in a higher relative to the m-PXAs analogues. Furthermore, the tricyclic unit endowed the polyesters with a superior gas barrier performance. Notably, the PXD film exhibited oxygen (O) and carbon dioxide (CO) barrier capabilities that were 3 and 7 times greater than those of polylactic acid (PLA), respectively. All amorphous polyesters allowed efficient recovery of DGX under mild conditions, with a yield of 93% achieved, and the recycled polymers displayed properties comparable to those of the virgin materials, thus demonstrating the potential for closed-loop recycling. This work presents a viable strategy for designing high-performance, sustainable biobased polyesters with end-of-life utility.
Thermally resistant polymers are extensively used in packaging, electronic products, and automobiles, while synthesizing high glass transition temperature polymers from biomass remains challenging. Herein, a series of bi...Thermally resistant polymers are extensively used in packaging, electronic products, and automobiles, while synthesizing high glass transition temperature polymers from biomass remains challenging. Herein, a series of biobased poly(cyclohexanedimethylene--2,2,4,4-tetramethyl-1,3-cyclobutylene thiophenedicarboxylate) (PCBTh) copolyesters were synthesized via a conventional two-step melt polycondensation method using biobased 2,5-thiophenedicarboxylic acid. The comprehensive properties of PCBTh copolyesters, including thermal resistance, thermal stability, mechanical properties, gas barrier properties, and optical transparency, were systematically investigated. With the incorporation of rigid 2,2,4,4-tetramethyl-1,3-cyclobutanediol up to 50 mol % into the molecular chains, the glass transition temperature of PCBTh copolyesters was synergistically enhanced from 71.4 to 102.5 °C. Meanwhile, the tensile modulus and tensile strength increased to 1650 and 53 MPa, respectively, with an elongation at break of 38%. These results demonstrate that PCBTh copolyesters are promising biobased materials for high thermal resistance packaging applications.
Peptide-based intracellular delivery carriers are known for their biocompatibility, tunability, and ability to transport various macromolecular cargos. Among these, a naturally derived epsilon-poly-l-lysine (εPL) has bee...Peptide-based intracellular delivery carriers are known for their biocompatibility, tunability, and ability to transport various macromolecular cargos. Among these, a naturally derived epsilon-poly-l-lysine (εPL) has been studied for nucleic acid complexation and delivery. However, εPL lacks the amphiphilic properties necessary to stably complex proteins, interact with cellular membranes, or facilitate endolysosomal escape. Hydrophobic derivatives of εPL are rare, and their application in intracellular protein delivery has not yet been demonstrated. Here, we report amphiphilic phenyl carbamoyl guanidine (PhCG)-modified εPLs that enable the intracellular delivery of necrosis-inducing antibodies, leading to a dose-dependent reduction in cellular viability through caspase-independent, membrane-compromised cell death. Varying the degree of PhCG substitution identified an optimal ∼25-50% modification for effective antibody delivery. Binding assays indicate that synergistic noncovalent interactions─strengthened by local hydrophobicity, hydrogen bonding, and electrostatic forces─drive complexation and delivery. These findings establish PhCG-modified εPL as an efficient, serum-tolerant carrier for intracellular antibody delivery.
Piezoelectric hydrogel sensors are a recent innovation that combines the flexibility of hydrogels with the self-powering of piezoelectric materials. Here, we present a self-powered hydrogel strain sensor by incorporating...Piezoelectric hydrogel sensors are a recent innovation that combines the flexibility of hydrogels with the self-powering of piezoelectric materials. Here, we present a self-powered hydrogel strain sensor by incorporating piezoelectric Na.Bi.TiO nanoparticles into a dual-network hydrogel composed of poly(vinyl alcohol), acrylamide, and 2-acrylamido-2-methyl-1-propanesulfonic acid. The hydrogel exhibits excellent mechanical properties, achieving a tensile strength of 1.28 MPa, an elongation at break of 1127%, and strong tissue adhesion (55.97 kPa on porcine skin). The sensor delivers a maximum output voltage of 237.4 mV, a sensitivity of 17.99 mV under small compressive strain, and a broad tensile strain detection range of 30 to 400%. It reliably monitors both subtle physiological activities (facial expression, swallowing, pulse) and large joint movements. Moreover, it exhibits notable antibacterial performance via ultrasound-driven piezocatalysis, reducing bacterial viability to below 1.5%. This tough, adhesive, and antibacterial piezoelectric hydrogel sensor holds significant promise for wearable electronics and human-machine interfaces.
The coordination ratio between metal ions and ligands governs the density, strength, and dynamics of coordination bonds in metal-coordinated hydrogels. However, the relationship between coordination stoichiometry and hyd...The coordination ratio between metal ions and ligands governs the density, strength, and dynamics of coordination bonds in metal-coordinated hydrogels. However, the relationship between coordination stoichiometry and hydrogel properties remains insufficiently understood. In this study, dual-cross-linked poly(histidine methacrylamide) (PHisMA)-Ni hydrogels were fabricated by varying the HisMA:Ni molar ratio, enabling precise regulation of network architecture, mechanical performance, and relaxation behavior. Remarkably, by tuning the HisMA:Ni molar ratio, Ni ions generated multidentate coordination with HisMA groups, yielding extraordinary mechanical reinforcement, achieving up to 75-fold higher fracture strength, 55-fold higher Young's modulus, and 492-fold higher toughness. The hydrogels also exhibited strong strain-rate dependence, tunable viscoelasticity, extended relaxation time, excellent energy dissipation, and rapid recovery. Furthermore, the hydrogels displayed potent antibacterial activity against . These findings establish the control of metal-ligand coordination ratio as an effective design principle for engineering dual-cross-linked hydrogels with tailored mechanical and antibacterial functionality, holding great promise for biomedical and wearable applications.
Microgel bioinks have gained great potential in bioprinting and tissue engineering due to their excellent mechanical performance and versatile printability. However, the effect of microgel size on the mechanical properti...Microgel bioinks have gained great potential in bioprinting and tissue engineering due to their excellent mechanical performance and versatile printability. However, the effect of microgel size on the mechanical properties and printability remained to be thoroughly explored. In this study, we developed an injectable gelatin-elastin methacrylate (GelMA-ElaMA) microgel bioink with tunable microgel diameters (100-1000 μM) using a microfluidic approach. The bioink's mechanical properties were systematically characterized through compression tests, AFM nanoindentation, and finite element analysis (FEA). Larger microgel bioinks exhibited higher stiffness, whereas the smaller ones showed greater flexibility and fracture strain. The FEA results confirmed a size-dependent enhancement of the modulus at the microscale. The bioinks displayed excellent printability and could form complex 3D structures with high shape fidelity. Microgel size modulates the stiffness-dependent cell response. When magnetically functionalized, the system responded to external magnetic fields and supported cell viability above 90%. These findings established a theoretical basis for microgel bioink design with mechanical tunability.
Thermoplastic polyamide elastomers (TPAEs) possess excellent elasticity and low-temperature resistance, making them suitable for a wide range of applications. However, the performance of commercial TPAEs relies on expens...Thermoplastic polyamide elastomers (TPAEs) possess excellent elasticity and low-temperature resistance, making them suitable for a wide range of applications. However, the performance of commercial TPAEs relies on expensive and difficult-to-source polyamide-11 or polyamide-12 as the hard segment, which restricts their accessibility and increases production costs. In this study, a biobased TPAE was synthesized via simple successive ring-opening and condensation polymerization of inexpensive -caprolactam (-CL), biobased dimethyl-protected cyclic lysine (DMCL) pioneered by us, polyether, and a dibasic acid. The resulting elastomer exhibits excellent elasticity (elongation at break up to 1133%) that is retained even at low temperatures. The melting point of the hard segment could be tuned by varying the -CL molar ratio, reaching as low as 183.3 °C. Notably, an efficient multinuclear titanium (Ti4) catalyst facilitated the one-pot polycondensation even in the presence of high water content, yielding a product free of unreacted polyether. Additionally, the dimethylamino side groups impart intrinsic antibacterial properties to the elastomer. This unique combination of properties renders the developed TPAE highly attractive for high-value-added applications such as medical devices.
Moriam K, Owens CE, Kroo L
… +5 more, Ghann W, Uddin J, Pitkänen L, Hummel M, McKinley GH
Biomacromolecules
· 2026 Apr · PMID 41790969
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Man-made cellulose fibers from well-managed forestry provide an eco-friendly alternative to polyester and cotton. The Ioncell process converts cellulose-based raw materials into high-quality textiles and offers strong po...Man-made cellulose fibers from well-managed forestry provide an eco-friendly alternative to polyester and cotton. The Ioncell process converts cellulose-based raw materials into high-quality textiles and offers strong potential for upcycling cellulose-based textile waste. Recycling discarded textiles is challenging because washing and abrasion degrade synthetic and natural fibers, reducing molecular weight and processability. Here, we demonstrate that adding a very small fraction of ultrahigh molecular weight bacterial cellulose enhances the spinnability of textile waste streams dominated by short-chain cellulose. This high molecular weight dopant systematically increases solution extensibility, stabilizing the extension-dominated fiber-spinning process. Viscoelastic stresses in a stable spinline scale with steady extensional viscosity at high strain rates and depend sensitively on chain extensibility. We quantify the enhanced tensile stress differences using capillarity-driven extensional rheometry combined with transient exponential shear rheometry to develop a metric for cellulose/ionic liquid solutions. These findings advance strategies for efficient recycling of postconsumer cellulose textiles.
Water-in-water (W/W) emulsions offer high biocompatibility for enzymatic processes but are difficult to stabilize with conventional oil-water surfactants due to their ultralow interfacial tension. Here, we design a gelat...Water-in-water (W/W) emulsions offer high biocompatibility for enzymatic processes but are difficult to stabilize with conventional oil-water surfactants due to their ultralow interfacial tension. Here, we design a gelatin-stabilized PEG/dextran (PEG/Dex) emulsion platform enabling integrated "reaction-separation-recovery" biocatalysis. By tuning the pH and polymer concentration, programmable microarchitectures such as core-shell, Janus, or triple-phase droplets were achieved. In cascade oxidation of guaiacol, the compartmentalized system reached an 86% yield of tetraguaiacol─50% higher than isolated phases─due to efficient product partitioning into the PEG phase while enzymes were retained in the gelatin phase. Catalytic efficiency (/) increased by 2.20-fold for glucose oxidase and 1.31-fold for horseradish peroxidase compared to buffer. Postreaction cooling (4 °C) triggered Gel gelation, enabling enzyme recovery with >70% activity retained after 3 cycles. This fully aqueous and recyclable platform demonstrates significant potential for enzyme engineering, bioactive compound synthesis, and green manufacturing.
The concurrence of drug-resistant infections and malignant tumors poses a serious challenge to clinical treatment, demanding multifunctional biomaterials with integrated therapeutic efficacy. In this study, we developed...The concurrence of drug-resistant infections and malignant tumors poses a serious challenge to clinical treatment, demanding multifunctional biomaterials with integrated therapeutic efficacy. In this study, we developed D-peptide engineered double-network (DN) hydrogels by combining a mechanically robust GelMA framework with a bioactive D-peptide (ik3) that exhibited broad-spectrum antibacterial and antitumor properties. The DN architecture provides improved toughness and stability under physiological conditions, while the incorporation of the ik3 peptide enhances proteolytic resistance and ensures sustained bioactivity. experiments demonstrated efficient inhibition of both Gram-negative and Gram-positive bacterial growth as well as apoptosis induction in a variety of tumor cell lines. Overall, these findings support D-peptide modified DN hydrogels as a promising multifunctional platform for synergistic infection control and tumor therapy.
Ionogels, as soft ionic conductors, face synthesis challenges including toxicity, complexity, and high energy consumption. Herein, we present a green one-pot strategy that effectively dissolves cellulose and undergoes su...Ionogels, as soft ionic conductors, face synthesis challenges including toxicity, complexity, and high energy consumption. Herein, we present a green one-pot strategy that effectively dissolves cellulose and undergoes sunlight-induced photopolymerization to form ionogels without the need for cross-linkers or initiators. 1-Butyl-3-methylimidazolium chloride ([BMIM]Cl), as the solvent, enables the disruption of the extensive hydrogen-bond network of cellulose, resulting in rapid and complete dissolution. Subsequent one-step photopolymerization, which proceeds solely under sunlight, simultaneously drives in situ cross-linking and a controlled phase separation process, yielding high-performance ionogels. Importantly, the resulting cellulose ionogel exhibits superior fracture strength (2.75 MPa), high toughness (18.4 MJ m), and strong adhesion (6.6 MPa), ameliorating the traditional trade-off between mechanical strength and adhesion capabilities. This work develops an integrated ionogel platform as a soft TENG electrode for human motion monitoring, informing the design of sustainable self-powered electronics.
Poly(3-hydroxybutyrate) (PHB) has long been recognized as a promising biobased and potentially biodegradable polymer; however, its brittleness and narrow processing window limit broader implementation. Copolymerization w...Poly(3-hydroxybutyrate) (PHB) has long been recognized as a promising biobased and potentially biodegradable polymer; however, its brittleness and narrow processing window limit broader implementation. Copolymerization with 3-hydroxyvalerate (3HV) improves flexibility and thermal behavior, yet controlling elevated 3HV incorporation in wild-type strains remains metabolically constrained. This work systematically investigates poly(3-hydroxybutyrate--3-hydroxyvalerate) (PHBHV) biosynthesis in H1 G3 DSM 545 as a benchmark production system, focusing on process limitations rather than record composition. The influence of cultivation mode (batch vs fed-batch), precursor chemistry (valeric acid vs sodium valerate), and pulse concentration was evaluated in relation to copolymer composition, molar mass distribution, and thermal properties. Under optimized conditions, 3HV contents up to 64 mol % were obtained. Increasing valeric acid concentrations led to reduced cell density and decreased 3HV incorporation, revealing a narrow precursor tolerance window. Using sodium valerate tends to promote biomass formation and 3HB biosynthesis at the expense of 3HV incorporation. A rapid, nondestructive FTIR method was developed to estimate 3HV molar fraction. These results clarify intrinsic metabolic boundaries governing 3HV incorporation and establish a framework for controlled structure-property investigation of PHBHV copolymers.
Rad N, Stasiak Z, Klak M
… +2 more, Wszoła M, Domański S
Biomacromolecules
· 2026 Apr · PMID 41780929
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Gelatin methacryloyl (GelMA) is an essential biomaterial for 3D bioprinting due to its excellent biocompatibility and easily tunable physical properties. GelMA quality strongly depends on the number of methacrylic groups...Gelatin methacryloyl (GelMA) is an essential biomaterial for 3D bioprinting due to its excellent biocompatibility and easily tunable physical properties. GelMA quality strongly depends on the number of methacrylic groups introduced during the synthesis. We present a direct UV assay for routine quantification of methacrylic groups in GelMA. The accuracy and precision of the method are comparable to those of NMR techniques. Moreover, the method is independent of sample concentration and adapted for gelatin from various sources. Additionally, we developed a UV-based method for determining methacrylic acid in GelMA and demonstrated how methacrylic acid contamination affects the quantification of methacrylic groups. Rather than reporting the degree of substitution alone, we define the methacrylic content as the quantity of methacrylic groups per 100 kDa gelatin unit, which makes the metric independent of the number of lysine residues in gelatin. This routine-ready approach lowers the barrier to reliable GelMA characterization and standardizes reporting across batches and laboratories.
Creating multifunctional hydrogel scaffolds that combine gradient conductivity with patterned morphologies to mimic the extracellular matrix and modulate neuronal behavior remains challenging. This study developed a cond...Creating multifunctional hydrogel scaffolds that combine gradient conductivity with patterned morphologies to mimic the extracellular matrix and modulate neuronal behavior remains challenging. This study developed a conductive, morphology-gradient hydrogel using an electrophoresis-based strategy. A thermosensitive polyisocyanopeptide (PIC) hydrogel served as the matrix, while graphene oxide nanosheets (GO) migrated under an electric field, forming a continuous gradient. This gradient enabled spatially varying conductivity, microstructure, and fiber alignment. Adjusting field strength and electrode configuration allowed precise control over GO distribution and patterned morphologies. SH-SY5Y cells aligned along the gradient, with higher GO regions promoting greater cell circularity and smaller cell areas than low-GO regions and controls. This work provides new insights into designing programmable multigradient conductive hydrogels, holding strong potential for advancing neural tissue engineering.