Journal of Materials Chemistry B最新文献

Engineering physiologically relevant liver models that can replicate infection dynamics and enable real-time biomarker monitoring remains a critical unmet need in liver disease research and diagnostics. Here, we present a modular, vascularized 3D in vitro liver model using core–shell microscaffolds designed to emulate the hepatic sinusoidal architecture and inflammatory microenvironment. The system co-encapsulates Huh-7 hepatocytes and liver sinusoidal endothelial cells (LSECs) with HUVECs in two distinct regions of the scaffold, the core and shell, respectively, promoting endothelial–hepatocyte cross-talk and secretion of regenerative cytokines including HGF, IL-8, and G-CSF. Upon Escherichia coli infection, the model exhibited reduced albumin levels and upregulated expression of key inflammatory markers, replicating infection-induced hepatic stress. To enable temporal biomarker tracking, we integrated the microscaffold model with a label-free, three-electrode electrochemical biosensor for detecting antibody binding changes using square wave and cyclic voltammetry (SWV/CV). This allowed real-time, non-invasive quantification of IL-6, CRP, and PCT over two weeks, with high sensitivity, which was further corroborated by the standard detection method of ELISA. This bioengineered platform uniquely combines a tissue-mimetic structure, regenerative biology, and real-time biosensing, offering a powerful tool for infection modelling, sepsis diagnostics, and therapeutic screening. Its modularity and scalability position it as a bioengineered platform for studying infection dynamics and enabling pre-clinical therapeutic screening in a physiologically relevant 3D microenvironment.

Infected skin defects persist in a pathological state characterized by dysregulation of the immune microenvironment and impaired bioenergetics, requiring coordinated treatment strategies to remold them. Currently developing therapies with coordinated effects are often hampered by incomplete targets, high complexity, and limited clinical performance, underscoring the need for minimalist yet effective strategies that integrate both targets. Here, we address this challenge by designing a two-component system, the polyphosphate–gallic acid (polyP-GA) complex, with high biocompatibility and adaptability to different material forms (e.g., solution, spray, hydrogel, and paste). Based on the mutually complementary and enhanced effects of the two constituents, the polyP-GA complex markedly inhibits bacterial infection, reduces reactive oxygen species (ROS) accumulation, and suppresses inflammation evidenced by facilitated macrophage polarization toward the reparative M2 phenotype and broad related anti-inflammatory transcriptional effects. Concurrently, the polyP-GA complex restores mitochondrial function and elevates intracellular adenosine triphosphate (ATP) levels, thereby activating pathways essential for fibroblast migration and angiogenesis. In a mouse model of infected skin defects, application of the polyP-GA complex (in the form of hydrogel and spray sequentially) significantly accelerated wound closure, enhanced collagen deposition and neovascularization, and promoted functional tissue remodeling. This work demonstrates that the minimalist therapeutic design, built on the synergistic pairing of biocompatible but otherwise subtherapeutic agents polyP and GA, can effectively break the cycle of infection-driven regenerative arrest, achieving high performance in promoting the healing of infected skin defects.

Chronic or non-healing wounds remain a major clinical challenge, driven by sustained inflammation and an unfavorable repair microenvironment. Type XVII collagen (COL17) is a key hemidesmosomal protein essential for keratinocyte adhesion and epidermal homeostasis. Nevertheless, whether exogenous COL17 can be harnessed as a therapeutic cue in otherwise conventional wounds remains unclear. Here, we combined COL17 with sodium carboxymethyl cellulose (CMC), a clinically familiar polysaccharide, to construct a composite hydrogel and examine its role in cutaneous repair. The CMC/COL17 hydrogels featured a uniform, extracellular matrix (ECM)-like porous network and showed COL17 dose-dependent viscoelastic enhancement, enabling them to form coatings that spread easily yet retain position on the wound. COL17 showed no cytotoxicity to fibroblasts across a wide concentration range and significantly enhanced their migration in vitro. In a murine full-thickness dorsal wound model, topical CMC/COL17 application accelerated wound closure, yielded a thicker and more continuous neoepidermis, improved collagen organization, and induced the early appearance of hair follicle-like structures. RNA sequencing of wound tissue showed suppression of inflammation- and chemotaxis-related pathways, including IL-17 and TNF signaling, with concurrent enrichment of cell–matrix interaction, cytoskeleton, and tissue development pathways. Consistently, at the cellular level, COL17 polarized macrophages toward an M2-like phenotype, suppressed pro-inflammatory cytokine expression, and reduced intracellular reactive oxygen species (ROS) in both fibroblasts and macrophages. Collectively, these results indicate that a simple CMC/COL17 hydrogel can couple a widely used cellulose carrier with a niche-relevant ECM protein to provide both anti-inflammatory and pro-regenerative effects, thus positioning COL17 as an active regulator in wound repair instead of solely a structural basement membrane component.

Diabetic wounds require an advanced wound care solution for faster recovery and reduced complications. In this direction, an injectable, self-healing hydrogel (HG) platform based on dynamic Schiff-base crosslinking between oxidized alginate (oAlg) and natural proteins (silk fibroin or Lathyrus sativus-derived plant protein) is developed for the treatment of infected diabetic wounds. The mild one-pot in situ fabrication enables the reduction of silver ions to silver nanoparticles (hereafter denoted as Ag) and the incorporation of graphene quantum dots (GQDs) into the HG matrix. This creates a synergistic antibacterial composite uniformly distributed within the HG network. The Ag–GQD combination that exhibits potent bactericidal and anti-biofilm activity against both Gram-negative (Escherichia coli) and Gram-positive (Micrococcus luteus) strains—comparable or superior to antibiotic, ciprofloxacin—through multi-modal mechanisms involving membrane disruption, reactive oxygen species generation, and impaired extracellular polymeric substance assembly. Both HGs demonstrate excellent hemocompatibility (<5% hemolysis), cytocompatibility (>80% cell viability), and shear-thinning injectability. In a streptozotocin-induced type-1 diabetic rat model of full-thickness infected wounds, the optimized silk fibroin-based Ag + GQD-loaded HG achieves complete re-epithelialization within nine days, with minimal inflammation, no scarring, and near-total bacterial eradication—significantly outperforming controls. This biocompatible, protein-reinforced oAlg HG formulation, leveraging sustainable nature-derived components and synergistic nanomaterial action, offers a promising antibiotic-free dressing to combat resistant infections and accelerate healing in chronic diabetic wounds.

Metastatic breast cancer remains a critical clinical challenge with limited therapeutic options, severe tumor metastasis and unsatisfactory single-treatment efficacy, and it is urgent to develop targeted and synergistic therapeutic strategies to improve anti-tumor outcomes. In this study, we developed a novel tumor-targeted nanomedicine (MFSE) based on exosome-modified mesoporous polydopamine (MPDA) loaded with saikosaponin D (SSd) and ferric ions (Fe³⁺) to achieve synergistic photothermal and drug therapies for improved anti-tumor efficacy. The internal pore size of MPDA matched the structural characteristics of SSd molecules, facilitating efficient loading and controlled release of SSd and preventing drug degradation. Importantly, Fe³⁺ doping enhanced the photothermal conversion efficiency by 38.68% compared with that of undoped MPDA. Owing to the homing effect of exosomes, MFSE exhibited superior cellular internalization and tumor accumulation. Upon 808 nm laser irradiation, the released SSd combined with the photothermal effect of MPDA to exert a synergistic anti-tumor effect, which effectively eliminated tumor cells, elicited immune responses, and significantly suppressed primary tumors, distant tumors, and lung metastases. Meanwhile, the MFSE-based therapeutic strategy displayed no obvious adverse effects and excellent biocompatibility in vivo. Overall, this study established a reliable and effective paradigm for the rational design of exosome-integrated nanoplatforms for precise targeting and synergistic therapy against metastatic breast cancer.

Mechanosensing interactions between the extracellular matrix (ECM) and the intracellular cytoskeleton are fundamental to cellular functions such as motility, proliferation, and adhesion, driven by the dynamic, bidirectional, tension-regulated maturation of focal adhesion (FA) sites. We demonstrate that native mechanosensing interactions and their downstream functions are precisely controlled using synthetic hydrogels. We introduce a microfluidic-assisted synthesis of imine-crosslinked hyaluronic acid-gelatin copolymer hydrogels (HAG), enabling controlled, predefined gradient viscoelasticity. Specifically, three native tissues (muscle, epidermis, and cartilage)-mimicking HAG hydrogels were prepared, matching their effective Young's modulus (Ymod) and stress relaxation time (τ_1/2). Enhanced cell spreading and directional cell migration are observed, with a preference for substrates with tissue-matching viscoelasticity. These mechanosensing reactions are confirmed by traction force microscopy, revealing a tight correlation between native tissue mechano-properties and the hydrogel viscoelastic parameters. We demonstrate that the signaling efficacies of the FAK and associated YAP/TAZ pathways, central regulators of FA formation and cell migration, are tuned by substrate tissue-matching viscoelasticity. We implement these preprogrammed viscoelastic gradient hydrogels as spatiotemporal cell-separation matrices, enabling viscoelasticity-driven migration of binary cell mixtures. This work provides a potent platform for studying cell-material interactions, offering significant potential applications in tissue engineering, immunotherapy, and regenerative medicine.

Periodontitis is an infectious and inflammatory disease that requires prolonged localized antibacterial and anti-inflammatory treatment. In situ forming gel (ISFG) drug delivery systems offer a promising approach for localized periodontal drug delivery. Poloxamer 407 (P407) is a well-reported thermosensitive polymer for ISFG systems; however, its low mechanical strength limits its ability to withstand in vivo stress. Herein, we utilized polyethylene oxide (PEO) to increase the mechanical strength of poloxamer 407 (P407)-based in situ gels, particularly for periodontal delivery of antibacterial (metronidazole) and antioxidant/anti-inflammatory drugs (curcumin). First, two types of formulations were developed: one containing the hydrophilic drug metronidazole (MTD) and the other with hydrophobic curcumin-loaded zein nanoparticles (CZ) to evaluate the effect of PEO. The prepared systems were assessed for gelation time, gelation temperature, syringeability, gel hardness, adhesiveness, drug release, and degradation. The addition of PEO significantly enhanced gel hardness, adhesiveness, and the syringeability force (but within a reported acceptable limit of 40 N); however, PEO did not affect the release of MTD. The cytocompatibility of the formulations was not compromised by the presence of PEO. CZ-loaded gels also exhibited antioxidant and anti-inflammatory activities via DPPH scavenging assay and in LPS-polarized macrophages, respectively. The P407 system with curcumin nanoparticles showed a significant increase in syringeability force during storage, whereas the PEO-P407 system maintained stable syringeability over 2 months. Lastly, both drugs were incorporated into a single formulation with PEO, and their release profiles were comparable to those observed in formulations containing the individual drugs. This indicates that the combined formulation did not adversely affect the release of either drug nor influence the antibacterial activity. In conclusion, these findings indicate that PEO can improve both the mechanical properties of ISFG and stability of nanoparticles-loaded P407-based gels with the ability to deliver hydrophilic and hydrophobic drug-loaded nanoparticles.

Supramolecular peptide assemblies generally rely on ionic groups for solubility in aqueous media but charge may sometimes affect their biological functions. Cationic residues in these assemblies are often associated with cell toxicity, and charged amino acids lead to supramolecular structures that are dependent on both pH and ionic strength. We report here on the synthesis of a nonionic peptide amphiphile (PA) containing a decaethylene glycol segment and its supramolecular co-assembly with ionic PA monomers as a strategy to produce uncharged assemblies and to fine tune charge density. We show that while morphology and internal structure depend on counterion screening and on pH for charged PA assemblies, these nonionic molecules self-assemble to form high-aspect ratio filaments containing β-sheets stable with or without ion screening and at acidic, neutral, and basic pH. By co-assembling nonionic PA molecules with charged PA molecules, we could produce supramolecular copolymers with tunable surface charge density, yet with stronger internal order than either fully charged or fully uncharged assemblies. Using an in vitro model for osteogenic differentiation of mesenchymal stem cells, we found that supramolecular assemblies containing nonionic molecules or co-assemblies of both nonionic and ionic PA molecules exhibit greater bioactivity than assemblies containing only charged molecules. We hypothesize that the enhanced bioactivity originates in the synergy between protein binding by PA molecules and increased supramolecular dynamics introduced by the nonionic ethylene glycol segments. Thus, nonionic PAs and their co-assemblies can be used to investigate how charge density and other factors affect bioactivity of water-soluble supramolecular nanostructures.

Amphiphilic porphyrin nanomicelles have been established as new single-molecule photodynamic agents (PDAs) for cancer treatment. Further improvement of the photodynamic performance will increase the potential of this class of PDAs for practical application. Here, we prepare four new porphyrin compounds F-TSCnP (n = 5–8) that bear a n-C₅F₁₁, n-C₆F₁₃, n-C₇F₁₅, and n-C₈F₁₇ chain, respectively. We demonstrate that, compared with the analogues that bear a shorter perfluoroalkyl or n-C₈H₁₇ chain, n-C₈F₁₇-bearing compound F-TSC8P can self-assemble into nanomicelles that possess increased stability and uniformity as well as improved intracellular self-delivering capacity. We further illustrate that nanomicelles formed by F-TSC8P form a unique fluorocarbon microphase, which can enrich and deliver O₂ to achieve remarkably enhanced photosensitizing activity for ¹O₂ generation. In vivo assay using a mouse model reveals that, compared with the fluorine-free counterpart, F-TSC8P, which has a therapeutic index of 10, exhibits a 150% increase in photodynamic activity for tumour growth inhibition.

Label-free optical recording of bioelectric potentials provides a non-perturbative approach for detecting bioelectric activities. Electrochromic materials, such as PEDOT:PSS, change their optical absorbance under external voltages. The voltage-dependent absorbance change allows recording of bioelectric potentials without using fluorescent reporters, and does not suffer from photobleaching or phototoxicity. Nevertheless, the voltage recording sensitivity of PEDOT:PSS strongly depends on its electrochromic properties. Here, we investigated how electropolymerization conditions of PEDOT:PSS thin films, including counterions, pH, PSS molecular weight, and substrate surface treatment, influence their electrochromic response. We found counterion competition is the dominant factor: introducing Cl⁻ as a competing counterion in addition to PSS during PEDOT electropolymerization blue-shifts the π–π* absorption peaks by ∼120 nm, alters film morphology and electrochromic response, and enhances optical anisotropy. At the same time, it reduces the voltage-dependent absorbance change at shorter (blue-green) wavelengths while enhancing it at longer (red) wavelengths. Using PEDOT:PSS thin films electropolymerized without Cl⁻ and a 561 nm laser, we achieved a voltage detection sensitivity of 2.8 µV at 10 kHz recording bandwidth under shot-noise-limited conditions. We then performed prolonged label-free optical recording of isolated embryonic chicken hearts. We recorded both the cardiac field potentials and mechanical contractions, which increased from embryonic day 10 to day 15, while the latency time between them remained unchanged. These results established electropolymerization as a strategy to tune the electrochromic response of PEDOT:PSS thin films across different wavelengths, thereby optimizing their voltage detection sensitivity.