Correction for ‘Magnetic lanthanum-doped hydroxyapatite/chitosan scaffolds with endogenous stem cell-recruiting and immunomodulatory properties for bone regeneration’ by Qiyang Wang et al., J. Mater. Chem. B, 2020, 8, 5280–5292, https://doi.org/10.1039/D0TB00342E.
To circumvent the lingering limitations of photodynamic therapy, we developed a novel naphthalene-derived endoperoxide through structural optimization of 1,4-dimethylnaphthalene. Strategic introduction of an amide group at the 2-position enabled precise modulation of steric and electronic properties, resulting in prolonged 1O2 release half-life (t1/2 = 8.6 h) compared to simpler derivatives. This temporal control is likely to result in more 1O2 release in tumor tissues, significantly enhancing the therapeutic effect. Our studies reveal that thermal cycloreversion drives 1O2 generation from these compounds, achieving potent cytotoxicity in cancer cell cultures (IC50 = 11.6 µM). In vivo evaluation using a murine 4T1 breast cancer model demonstrated marked tumor suppression following intraperitoneal administration, with no observable systemic toxicity at the therapeutic doses. To enable real-time evaluation of therapeutic efficacy, we designed a modular system combining a naphthalimide fluorescent group with an H2O2-responsive phenylboronic ester. This construct capitalizes on the pathological overproduction of H2O2, a well-established biomarker of tumor progression. When exposed to elevated H2O2 levels in cancer cells, the phenylboronic ester undergoes specific cleavage to generate hydroxyl groups. This structural transformation triggers a blue-to-green fluorescence emission change, providing direct visual confirmation of therapeutic activation within the tumor microenvironment.
A systematic understanding of how the density of neural stem/progenitor cells (NS/PCs) embedded within three-dimensional (3D) biomaterials affect cell behavior will be necessary for developing effective strategies to generate CNS tissues. Here, we investigated the effects of local and global cell density of mouse neural stem cells (mNSCs) on their viability, proliferation, and differentiation when cultured in 3D, hyaluronic acid (HA)-based hydrogel matrices. Specifically, we assessed the influence of spheroid size, which represents local cell density, (small: 100 cells per sphere, large: 200 cells per sphere) and seeding density (low: 100 000 cells per hydrogel, high: 200 000 cells per hydrogel), which represents global density, on cellular outcomes. Results reveal that these factors have both independent and interactive effects on NS/PC viability and fate. Cultures of smaller spheres at low global densities yield more glial cells, including astrocytes and oligodendrocytes. In contrast, cultures with high global densities, regardless of sphere size, better preserved stem-like mNSC phenotypes. Strikingly, cultures with 1000 total spheres per hydrogel, regardless of sphere size or overall cell concentration, best maintained viability while promoting neuronal maturation. These findings highlight the importance of controlling both local and global cell densities in 3D cultures to achieve reproducible mNSC-derived populations for use as in vitro test beds or biomanufacturing of therapeutic stem cells.
Ferroptosis is a form of cell death characterized by decreased glutathione peroxidase 4 (GPX4) activity and amplification of lipid peroxidation cascades, efficiently disrupting cellular redox homeostasis. Photothermal therapy effectively regulates System Xc−, leading to the downregulation of GPX4, which plays a crucial role in promoting ferroptosis. However, the cellular self-protection mechanism of thermotolerance subsequently becomes a negative factor. Sonodynamic therapy (SDT) accumulates singlet oxygen (1O2), which facilitates the maintenance of reactive oxygen species and effectively alleviates thermotolerance during thermal elevation, while creating conditions for lipid peroxidation. This study constructed a nanodrug IrOx@HMME-HSA, in which the iridium oxide (IrOx) component guides photothermal effects and regulates the System Xc−–glutathione (GSH)–GPX4 route, and hematoporphyrin monomethyl ether (HMME) enables SDT to generate ROS and lipid peroxides and eliminate heat resistance. This provides a novel strategy to address the self-hypoxic characteristics of tumor microenvironments, antioxidant defenses, and laser-responsive heat tolerance issues. In addition, it lays theoretical and experimental foundations for the application of iridium-based nano-drugs in cancer therapy enhanced by ferroptosis through amplified GSH depletion.
Ocular diseases impose significant therapeutic challenges due to drug delivery barriers and limitations of current treatment procedures. This review explores how aggregation-induced emission (AIE) technology offers advantages over conventional treatments by unifying precision imaging and targeted therapy. AIE luminogens exhibit significantly enhanced fluorescence and reactive oxygen species (ROS) generation in aggregated states, enabling real-time visualization and spatiotemporally controlled intervention. Crucially, AIE platforms address key constraints of existing approaches: their physical antimicrobial mechanism bypasses antibiotic resistance, light-activated delivery leverages ocular translucency to replace invasive injections, and organelle-level specificity minimizes collateral damage compared to systemic agents. For selected intractable conditions, including infections and retinal degeneration, this integrated “see-and-treat” paradigm demonstrates significant transformative potential for advancing vision-preserving ophthalmology.
Hydrogels are water-rich, three-dimensional polymeric networks that closely mimic the physical and mechanical properties of native tissues, making them highly suitable for biomedical applications. Among these, in vivo applications are particularly significant, as they involve direct interactions with the internal physiological environment to support diagnosis, therapy, and tissue regeneration. Given the rapid advancements and growing complexity of in vivo hydrogel technologies, a comprehensive and up-to-date overview is needed to contextualize current progress and guide future research. This review begins by introducing the hydrogel selection and key properties of medical-grade hydrogels, including their mechanical performance, biocompatibility, and responsiveness. We then examine recent advances in in vivo applications, with an emphasis on 3D bioprinted hydrogels for tissue reconstruction, hydrogel-based implantable electronics for sensing and stimulation, implantable hydrogel adhesives, and hydrogel systems for wound healing and regenerative therapies, such as cartilage repair and neural regeneration. We also highlight hydrogel platforms for drug delivery and microneedle-based systems designed for biosensing and controlled therapeutic release. Throughout this discussion, we analyze the material properties and performance requirements specific to each in vivo use case. Finally, we outline key challenges such as immune compatibility, mechanical stability, and long-term functionality, and provide perspectives on strategies to accelerate clinical translation and enhance the functional versatility of hydrogel technologies. This review aims to offer valuable insights and inspiration for researchers seeking to advance the development of hydrogel-based in vivo biomedical applications.
Endoscopic submucosal dissection (ESD) is currently an important minimally invasive treatment for early gastrointestinal tumors. However, there remains a lack of ideal materials that can not only provide good injectability and submucosal lifting performance during ESD but also promote wound repair after ESD. This study aims to evaluate the properties of a novel polysaccharide material—colanic acid (CA). A comprehensive comparison was conducted between CA and clinically commonly used materials (normal saline and hyaluronic acid (HA)) in terms of physicochemical characteristics, submucosal lifting capacity, and biocompatibility. The results showed that CA exhibited better injectability, adhesiveness, and lifting performance than HA, and it showed no detectable cytotoxicity, hemolytic activity, or adverse local/systemic tissue reactions in our experiments. Additionally, CA demonstrates superior biological activities than HA, such as promoting angiogenesis, exerting antioxidant effects, inhibiting the secretion of IL-6, TNF-α, and IL-1β to achieve anti-inflammatory effects, and facilitating the migration of gastric epithelial cells. In an in vivo ESD model in pigs, it was verified that CA has better lifting performance than HA, and it could shorten the cutting time and reduce the number of injections during ESD. Furthermore, transcriptomic results suggest that CA promotes the enrichment of pathways related to wound healing compared with HA. This finding was further validated in a gastric ulcer model in rats, and the results indicate that CA has a better ulcer repair effect than HA. In conclusion, by integrating excellent physicochemical properties and multi-dimensional biological activities, the CA polysaccharide achieves synergistic optimization of procedural convenience, operational safety, and efficient wound healing across pre-, intra-, and post-operative phases of ESD, demonstrating promising clinical application prospects.
The invasive nature of brain implants remains a major limitation in neuromodulation strategies, often leading to chronic inflammation. To address this, soft coatings are applied on rigid probes to reduce the mechanical mismatch at the interface, or flexible probes are implemented accompanied by temporary stiffeners. This study presents a hybrid strategy integrating both approaches by applying a permanent hydrogel coating onto flexible neural probes. Moreover, we utilise the applied coatings as tool for post-operative non-invasive imaging via functionalisation of the hydrogel with 5-acrylamido-2,4,6-triiodoisophthalic acid (AATIPA), a monomer that increases radiodensity. Rheological measurements confirmed that AATIPA incorporation did not significantly alter the hydrogels’ mechanical properties (storage moduli ranging from 139 ± 33.5 to 186 ± 55.5 kPa). Subsequently, we show that coated flexible probes exhibited a two-fold increase in critical buckling force compared to uncoated counterparts, indicating improved mechanical robustness evidenced through enhanced insertion performance in agarose brain phantoms. The mechanical contrast supports the dual purpose of the material in our application: the coatings provide stiffness to facilitate probe insertion in the dry state, while transitioning to a compliant, soft interface upon swelling, post-implantation. Finally, the radiodense coating enabled successful visualization of the probes in the hippocampus of a mouse model using μ-CT imaging. This approach offers a promising route for improving the mechanical and imaging performance of neural implants, potentially reducing reliance on post-mortem histology and enhancing real-time feedback in neuromodulation research.
Prolonged urinary catheterization often leads to two major complications, bacterial biofilm formation and fibrotic tissue development, both of which hinder catheter function. However, current catheter designs fail to address these challenges simultaneously. In this study, the surface of a polyvinyl chloride (PVC) catheter was conjugated with TetraF2W-RR, an antimicrobial peptide (AMP) effective against drug-resistant methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (MDRPA) strains, and DR8, an antifibrotic peptide (AFP) that inhibits excessive extracellular matrix (ECM) buildup to provide both antimicrobial and antifibrotic effects. Covalently co-immobilizing TetraF2W-RR and DR8 peptides onto PVC surfaces (PVC–AMP/AFP) via cold atmospheric plasma (CAP) created dual-functional urinary catheters that prevent biofilm formation by MRSA and MDRPA while diminishing fibrotic responses in vitro. PVC–AMP/AFP surfaces demonstrated strong antibacterial and antibiofilm activity without harming NIH 3T3 cells. In a TGF-β1-stimulated fibroblast model, PVC–AMP/AFP catheter groups significantly reduced fibrotic gene expression (COL1A1, FN1, ACTA2, and TGF-β1), lowered total collagen levels, and decreased COL1A1 and α-SMA expression by immunofluorescence staining. A wound healing assay in a TGF-β1-induced fibrotic fibroblast model further confirmed suppressed fibroblast migration in PVC–AMP/AFP catheter groups. To the best of our knowledge, this is the first attempt to simultaneously impart antibacterial and antifibrotic functionalities to PVC urinary catheters via covalent co-immobilization of AMP and AFP. This combined approach offers a promising strategy to improve the long-term safety and efficacy of indwelling urinary catheters and could be applied to a variety of implantable biomaterials.
Liquid multisensors are in high demand due to their wide range of applications. Recent advances in electronics allow an integration of several individual devices for target and control measurements on one chip. We studied aptamer-modified electrolyte-gated field-effect transistors (EGOFETs) as basic sensor elements for single-chip multitarget detection. We used an aptamer with a pH-dependent conformational switch as a model recognition element allowing application of the EGOFET as a single element for detecting three targets of different nature. The fabricated EGOFET device has been shown to be sensitive to the conformation of the aptamer. The sensor is sensitive to the pH changes in the range of pH 6–8 due to the H+-dependent assembly of an i-motif DNA structure. Under the i-motif-unfavorable conditions (pH ≥ 7.3), the unfolded cytosine loop forms a complex with Ag+ ions providing a new conformation. Finally, under the i-motif-favorable conditions (pH < 7.3), the folded i-motif binds to influenza A virus. The EGOFET signals for these three analytes lie in different ranges allowing their clear discrimination. Applicability of the designed device under biologically relevant conditions was proved for biological fluids such as saliva and plasma with a viral load typical for patients with influenza. The proof-of-concept for single-chip multitarget detection based on EGOFETs with one recognition element is implemented for the first time. This example of the model recognition element with combined properties integrated into the EGOFET paves the way to managing the properties of the EGOFET-based biosensors and, in the future, to developing single-chip multisensors on the EGOFET platform.
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