Journal of materials chemistry. B最新文献

Ultrasound (US) offers exceptional tissue penetration, making it a promising modality for the treatment of deep-seated cancers. Sonodynamic therapy (SDT) leverages US to activate low-toxicity sonosensitizers, generating cytotoxic reactive oxygen species (ROS) that induce cancer cell death. However, its clinical effectiveness is hindered by challenges such as hypoxia and overexpression of glutathione (GSH) in the tumor microenvironment (TME). In this study, we designed and synthesized a sodium-hyaluronate-modified TCCP-BSO@CaO₂@SH nanoplatform (TBC@SH NPs) to enhance SDT efficacy in hepatocellular carcinoma (HCC). The TBC@SH NPs were prepared through a straightforward one-pot method, involving the self-assembly of CaO₂ nanoparticles with tetrakis (4-carboxyphenyl) porphyrin (TCPP) and L-buthionine sulfoximine (BSO), followed by surface modification with sodium hyaluronate (SH) for targeted delivery to CD44 receptors on HCC cells. In the mildly acidic TME, TBC@SH NPs facilitate oxygen release, induce calcium ion overload, inhibit GSH synthesis, and generate substantial reactive oxygen species (ROS) under ultrasound irradiation. These synergistic effects collectively amplify oxidative stress, significantly enhancing SDT therapeutic efficacy in HCC treatment. Encouraging results were observed in both in vitro HCC cell models and in vivo animal tumor models. This study highlights the potential of ultrasound-mediated SDT therapy for HCC and provides valuable insights into the development of integrated nanoplatforms for enhanced HCC treatment.

The development of advanced biomaterials with multifunctional properties is essential to address the complex challenges of impaired wound healing and tissue regeneration. This study introduces a novel composite scaffold (SSP-CG), in which silk sericin (SS) and polyvinyl alcohol (PVA) form the SSP component, while copper nanoparticles (CuNPs) and gallic acid (GA) constitute the CG component. SS provides biocompatibility and biodegradability, while PVA enhances structural integrity. CuNPs and GA impart antimicrobial and antioxidant activity, respectively, making the scaffold highly suitable for biomedical applications. The scaffold features an optimal pore size (96 ± 19 μm) and pore volume, promoting cell infiltration and nutrient diffusion. In vitro degradation studies revealed a controlled, sustained profile over 6 weeks, ideal for long-term therapeutic use. A gradual and prolonged release of GA ensured continuous antioxidant activity, confirmed by a DPPH assay showing significant free radical scavenging activity (40.5 ± 2.1%). In vitro studies further confirmed excellent biocompatibility, with optimal cell adhesion, proliferation, and viability while maintaining the environment for tissue regeneration. In vivo studies demonstrated superior wound healing outcomes for the SSP-CG scaffold compared to both positive and negative controls, with histological analysis further confirming enhanced tissue regeneration and reduced inflammation. This first-of-its-kind integration of SS, PVA, CuNPs, and GA highlights the synergistic benefits of these components, offering a promising solution for advanced wound healing and tissue regeneration. These findings suggest that SSP-CG scaffolds could contribute to next-generation biomaterials tailored for chronic wound management and regenerative therapies.

Thermoresponsive biomaterials have the potential to improve the complexity of in vitro models, to generate dynamically controlled extracellular microenvironments and act as in situ forming drug delivery systems. Due to its known biocompatibility and ease of use, poloxamer 407 (P407), also known as pluronic F127, has attracted significant attention as a component for next-generation cell culture and biomedical applications. P407 display rapid gelation into hydrogels with facile ease-of-handling, and which possess good shear-thinning properties that enable 3D printability with high fidelity. Although P407 has been extensively used as a support matrix for cell proliferation, differentiation and the on-demand release of biomolecules and drugs, significant issues relating to mechanical stability under physiological conditions limit its application. Multiple protocols report the use of P407 'hydrogel' for a variety of applications but often do not emphasise its inherent limitations at the concentrations described. Here we emphasise the disparity between written protocols and what specifically constitutes a hydrogel, showing selected examples from the literature and suggesting clarifications in the language used in describing P407 supports. We describe progress in the field, which is accelerating in part due to development of multi-network hydrogels that include P407 as a stabiliser, for shear-thinning and as a sacrificial component aiding 3D printing. We also contrast P407 to a panel of other promising thermoresponsive systems that have emerged as alternative biomaterials. Finally, we briefly discuss challenges and new opportunities in the field. This includes evaluation of the relative merits of current thermoresponsive polymer systems as they are formulated for use, also by advanced manufacturing, in next-generation 4D-responsive functional hydrogel networks for cell culture automation and as components in responsive-release devices.

Ternary composite foam materials containing poly-L-lactic acid (PLLA), calcium hydroxyapatite (HAP) (20 nm), and morphologically controlled Fe₃O₄ nanoparticles (80 nm) were fabricated using the thermally induced phase separation (TIPS) technique over a broad concentration range of the magnetic component (1-30 wt%). The foam scaffolds were highly porous (>95%), and lightweight, with a high capacity for soaking in Ringer's solution. The foam density varied with the inorganic component content, ranging from 0.02 to 0.079 g mL^-1, while the mean pore size was approximately 330 μm. The magnetic behavior of Fe₃O₄ nanocubes and the foam composites was characterized. The presence of the inorganic filler caused a shift towards a lower decomposition temperature of PLLA. The conversion energy of both dry and Ringer's solution soaked foams was studied in detail demonstrating that the fabricated ternary composites are highly temperature-responsive under the influence of an alternating magnetic field (AMF), near-infrared (NIR) laser radiation (808, 880, and 1122 nm), and the synergistic effect of both external stimuli. This synergy resulted in faster heating and a higher maximum temperature (T_max ≈ 80 °C). Biological characterization and heating ability analysis enabled the selection of the most reliable foam, which contained 15% magnetic filler, based on its appropriate microstructure, sufficient biocompatibility, and ability to reach biologically relevant temperatures under AMF exposure and the combined action of NIR and AMF. The fabricated materials exhibit high potential for biomedical applications as well as other areas requiring temperature-controlled stimulation of various processes.

Radiotherapy (RT) faces hypoxia-induced radioresistance, as oxygen-deficient tumor regions limit reactive oxygen species (ROS) generation. Current hypoxia-targeting strategies (e.g., prodrugs, nanocarriers) struggle with inefficient delivery, off-target effects, and clinical translation barriers, necessitating advanced oxygenation or hypoxia-specific radiosensitization approaches. Herein, we developed pH-responsive BM-DOX@BSA nanoparticles (NPs) using a solvothermal method. Bi(NO₃)₃, MnCl₂, and TCPP were used as precursors, with DOX loaded for chemotherapy. BSA was added to enhance biocompatibility. In vitro and in vivo experiments assessed ROS generation, drug release, cytotoxicity, and tumor suppression efficacy under X-ray irradiation. BM-DOX@BSA NPs exhibited pH-responsive degradation, releasing DOX more rapidly in acidic conditions. They markedly increased the generation of ROS under X-ray irradiation, resulting in enhanced apoptosis of tumor cells and DNA damage. This effectively improved the efficacy of radiation dynamic therapy (RDT). In vivo, the NPs combined with RT achieved 100% tumor suppression in HepG2 tumor-bearing mice, demonstrating excellent biocompatibility and therapeutic efficacy.

Multifunctional nanoprobes combining magnetic resonance imaging (MRI) contrast as well as near infrared (NIR) imaging and thermometry are demonstrated by using quasi-bidimensional core-multishell nanostructures based on the scheelite-like NaLn(WO₄)₂ host (Ln = trivalent lanthanide). These nanostructures are composed of a NaHo(WO₄)₂ core, plus a first shell of Tm,Yb:NaGd(WO₄)₂, and a second shell of Nd,Yb:NaGd(WO₄)₂. Proton nuclear magnetic relaxation dispersion studies and MRI of water dispersions of nanoprobes, whose quasi-bidimensional geometries promote the interaction of Gd³⁺ with water protons, reveal behaviors evolving from a T₁-weighted MR contrast agent (CA) at 1.5 T to a highly effective T₂-weighted MR CA at ultrahigh magnetic fields of 7 T and above, and even a dual T₁/T₂-weighted CA at a clinical 3 T magnetic field. By NIR excitation (λ_EXC ∼ 803 nm) of Nd³⁺, luminescence-based thermometry was accomplished at wavelengths within the second biological transparency window (II-BW) through ratiometric analysis of ⁴F_3/2 → ⁴I_11/2 Nd³⁺ (λ = 1058 nm) and ²F_5/2 → ²F_7/2 Yb³⁺ (λ = 996 nm) emissions. Under a biologically safe excitation of 0.68 W cm^-2, a chemically stable 2 mg mL^-1 nanoprobe water dispersion presents absolute, S_A, and relative, S_R, thermal sensitivities as remarkable as S_A = 480 × 10^-4 K^-1, and S_R = 0.89% K^-1 at 40 °C (313 K), and temperature resolution δ ≈ 0.1 K. Moreover, through efficient Nd³⁺ → Yb³⁺ → Tm³⁺ and Nd³⁺ → Yb³⁺ → Ho³⁺ energy transfers, NIR photoluminescence from Tm³⁺ at ∼1800 nm and Ho³⁺ at ∼2000 nm facilitates in depth imaging. The low nanoprobe cytotoxicity allows NIR biolabeling during cellular temperature measurement.

Chronic nonhealing wounds represent significant complications of diabetes, bearing a substantial burden and posing risks of disability or mortality. In diabetic wounds, continuous tissue fluid exudation, inflammatory cell migration, fibrosis, and bacterial biofilm formation create a "barrier", which decreases the treating efficacy of therapeutics. To address these limitations, a recombinant human collagen type III microneedle patch (rhCol III-PRP^M) loaded with platelet-rich plasma (PRP) was developed, in which methacrylated rhCol III (rhCol III-MA) loaded with PRP was utilized to form needle tips, while rhCol III-MA formed the base part of the patch. RhCol III-PRP^M featured adequate mechanical qualities, swelling capacity, and sustained in vitro release of growth factors from the activation of PRP for over 7 days. Leveraging the synergistic effects of rhCol III and PRP, rhCol III-PRP^M patches facilitated cell proliferation, migration, and angiogenesis, and reduced oxidative stress. In animal experiments, this microneedle patch effectively promoted the healing of diabetic wounds during a 20-day treatment, partially due to upregulating integrins and phosphorylated ERK protein levels. Diverging from other microneedle strategies, the rhCol III exhibited "dual functionality," serving as both the microneedle patch matrix and therapeutic agent, promoting wound healing upon patch dissolution while delivering PRP. The combination of rhCol III and PRP in the form of a microneedle patch offered a straightforward and efficacious way for effective diabetic wound management, and showed promise in bringing new possibilities in clinical practice.

Cartilage injury represents a significant clinical challenge, necessitating innovative repair strategies. Self-healing injectable hydrogels are emerging as promising solutions for cartilage regeneration. However, the hydrogel with robust mechanical strength mimicking the natural cartilage and appropriate extracellular matrix production has not yet been achieved. To address this challenge, we have fabricated self-healing injectable hydrogels by combining oxidized alginate (OA) and gelatin (G) with recombinant hyaluronic acid (HA) of varying molecular weights (0.5 MDa, 1.0 MDa, and 2.0 MDa) derived from metabolically engineered Lactococcus lactis. Incorporating HA resulted in improved physicochemical, mechanical, and biological properties. The 1.0 MDa HA-incorporated hydrogel (OAGH_1.0) exhibited superior injectability and self-healing efficiency due to the balance between dynamic covalent and non-covalent interactions within the hydrogel network. The OAGH_1.0 hydrogel's enhanced shear-thinning properties aided in printing the hydrogel into a mesh-like structure using a 3D printer. The OAGH_1.0 hydrogel showed an ultimate strength of 1.2 MPa, comparable to the natural cartilage. In vitro studies confirmed that these hydrogels also fostered cell adhesion, proliferation, and collagen deposition. These results indicate that the balance between dynamic covalent and non-covalent interactions achieved in the OAGH_1.0 hydrogel will open promising avenues for advancing cartilage regeneration.

The development of theranostic systems is of fundamental importance for the treatment of diseases. These systems should combine the features of fluorescent molecules that can act as diagnostic systems and species with therapeutic potential. Herein, we report the synthesis of a multifunctional halloysite nanotube (HNT)-based nanomaterial via the covalent modification of the external surface of the clay with a halochromic probe and the immobilization of Fe₃O₄ nanoparticles (HNTs-1@Fe₃O₄) with chemodynamic activity. The covalent modification of HNTs was performed using two different synthetic approaches, and the best strategy was evaluated by estimating the degree of functionalization of the clay via thermogravimetric analysis. The synthesized nanomaterial was thoroughly characterized, and its photoluminescence properties under different conditions, i.e. different solvents, pH conditions and temperatures, were studied. The HNTs-1@Fe₃O₄ nanomaterial was found to exhibit good peroxidase-like activity, as shown by testing its performance in the catalytic oxidation of the colorless enzyme substrate 3,3',5,5'-tetramethylbenzidine (TMB) to blue TMB oxide (ox-TMB) in the presence of H₂O₂. This study highlights the usefulness of the covalent approach for modifying halloysite surfaces to generate nanomaterials for potential tissue imaging under different stimuli. In addition, the combination with Fe₃O₄NPs led to the synthesis of multifunctional materials with potential use as theranostic systems for the treatment of diseases.

Micro/nanofibrous materials play an increasingly important role in tissue regeneration due to their ECM-mimicking properties and mechanical regulation capabilities. This study developed a microfiber fabrication method based on molten stringing of fused deposition modeling (FDM), successfully creating an ordered microfiber network with spatial structures. It surpasses the size limits of FDM filaments, enabling the precise fabrication of microfibers with diameters of 15-150 μm. The customizable PLA microfiberous-net was then encapsulated in GelMA hydrogel and mineralized in situ, effectively producing biomimetic bone repair materials with customization of surface microstructures and control of micromechanics, which in turn influences and regulates cell behavior. By adjusting the structure and density of the microfiber network, it is possible to control the compressive modulus, viscoelasticity, and tensile strength to match the micromechanical environment for cell spreading and proliferation. Additionally, the network structure can guide cell alignment and aggregation, influencing cell morphology and enabling controlled guidance of cellular behavior. Our simple and convenient microfibrous printing method holds great potential for the preparation of various fibrous materials for tissue regeneration.