Biomaterials Science最新文献

Background: Ulcerative colitis (UC) is a debilitating chronic inflammatory bowel disease, and current treatments primarily focus on suppressing inflammation with limited efficacy. However, the resolution of inflammation also plays a crucial role in UC prognosis. Combining anti-inflammatory and pro-inflammatory resolution interventions may be a promising approach for treating UC. Materials and methods: The nano-bomb nanoparticles were validated for their ability to load CD98 siRNA (siCD98) and Annexin A1-mimetic peptides (Ac2-26 peptides), as well as release CO₂ upon lysosomal escape. Surface modification with hyaluronic acid (HA) was assessed for its capability to target inflammatory tissues and cells. Biocompatibility and biosafety were evaluated through in vitro and in vivo studies. The anti-inflammatory and pro-resolving effects of siCD98@NPs and Ac2-26@NPs, both individually and in combination, were evaluated by measuring ROS production, pro-inflammatory cytokine expression, CD98 gene expression, and macrophage polarization. Results: These nanoparticles could efficiently load siCD98 and Ac2-26 peptides and release CO₂ under acidic pH in the endo/lysosome to deliver drugs to the cytoplasm. HA could effectively target the inflammatory tissue and cells, showing good biocompatibility and biosafety both in vitro and in vivo. siCD98@NPs and Ac2-26@NPs showed anti-inflammatory effects by eliminating the over-production of ROS and down-regulating the expression of pro-inflammatory cytokines (TNF-α and IL-1β) and the CD98 gene; meanwhile, it showed pro-resolving function by inhibiting M0 to pro-inflammatory M1 macrophage conversion, with a more pronounced effect when combined with siCD98 and Ac2-26. The oral administration of chitosan-alginate hydrogel-encapsulated nanoparticles in UC model mice effectively alleviated inflammatory symptoms, reduced the expression of pro-inflammatory cytokines (TNF-α and IL-1β) and the CD98 gene, restored intestinal barrier function, and promoted M1 to M2 polarization, with a more pronounced effect when combined. Conclusion: By combining anti-inflammatory and pro-resolution interventions, these nanoparticles offer a novel therapeutic approach. This study offered a new approach for combination therapy of UC.

Cancer immunotherapy involves a cutting-edge method that utilizes the immune system to detect and eliminate cancer cells. It has shown substantial effectiveness in treating different types of cancer. As a result, its growing importance is due to its distinct benefits and potential for sustained recovery. However, the general deployment of this treatment is hindered by ongoing issues in maintaining minimal toxicity, high specificity, and prolonged effectiveness. Nanotechnology offers promising solutions to these challenges due to its notable attributes, including expansive precise surface areas, accurate ability to deliver drugs and controlled surface chemistry. This review explores the current advancements in the application of nanomaterials in cancer immunotherapy, focusing on three primary areas: monoclonal antibodies, therapeutic cancer vaccines, and adoptive cell treatment. In adoptive cell therapy, nanomaterials enhance the expansion and targeting capabilities of immune cells, such as T cells, thereby improving their ability to locate and destroy cancer cells. For therapeutic cancer vaccines, nanoparticles serve as delivery vehicles that protect antigens from degradation and enhance their uptake by antigen-presenting cells, boosting the immune response against cancer. Monoclonal antibodies benefit from nanotechnology through improved delivery mechanisms and reduced off-target effects, which increase their specificity and effectiveness. By highlighting the intersection of nanotechnology and immunotherapy, we aim to underscore the transformative potential of nanomaterials in enhancing the effectiveness and safety of cancer immunotherapies. Nanoparticles’ ability to deliver drugs and biomolecules precisely to tumor sites reduces systemic toxicity and enhances therapeutic outcomes.

The blood-based detection of Alzheimer's disease (AD) is becoming challenging since the blood–brain barrier (BBB) restricts the direct circulation of AD molecules in the blood, thereby precluding the detection of AD at an early-stage. Herein, we report the development of a novel CNT-metal-porous graphene hybrid (CNT-MGH) nano-interdigitated array (n-IDA) electrochemical 8-well biosensor for the successful early-stage diagnosis of AD from blood. Laser-induced graphene (LIG) technology has been used to fabricate the proposed CNT-MGH n-IDA 8-well sensor. Firstly, the electrochemical characterization (i.e., electrode gap, material composition, etc.) of the proposed sensor was demonstrated by measuring p-aminophenol (PAP) with a limit of detection (LOD) of 0.1 picomole. Subsequently, the CNT-MGH n-IDA 8-well sensor was then used to diagnose AD via novel blood biomarkers p-Tau 217 and p-Tau 181 using an electrochemical enzyme-linked immunosorbent assay (e-ELISA) enzyme by-product PAP. During e-ELISA, the alkaline phosphatase enzyme (IgG-AP) tagged to the detection antibody produced an electroactive ELISA by-product PAP by reacting with the enzyme–substrate 4-aminophenyl phosphate (PAPP). Finally, the CNT-MGH n-IDA 8-well sensor was then used to measure the current generated by the redox reaction via the e-ELISA by-product PAP. While quantified, the proposed CNT-MGH n-IDA 8-well sensor successfully detected p-Tau 217 and p-Tau 181 proteins in blood with LODs of 0.16 pg ml⁻¹ and 0.08 pg ml⁻¹, respectively.

Chemodynamic therapy (CDT) utilizing the Fenton reaction to convert hydrogen peroxide (H₂O₂) into cytotoxic hydroxyl radicals (˙OH) has recently drawn extensive interest in tumor treatment. However, the therapeutic efficiency of CDT often suffers from high concentrations of glutathione (GSH), insufficient endogenous H₂O₂ and inefficient Fenton activity. Herein, a GSH-depleting and H₂O₂ self-providing nanosystem that can efficiently load copper ions and doxorubicin (DOX) (MSN-Cu²⁺-DOX) to induce enhanced CDT and chemotherapy is proposed. The results show that MSN-Cu²⁺-DOX could release Cu²⁺ and DOX under acidic conditions. Particularly, both the released Cu²⁺ and Cu²⁺ in MSN-Cu²⁺-DOX are available for ˙OH production via a Fenton-like reaction for CDT. Meanwhile, Cu²⁺ undergoes a reduction to Cu⁺ by depleting overexpressed GSH, thereby enhancing CDT. Moreover, the released DOX could not only be used for chemotherapy, but also promote the generation of endogenous H₂O₂ to improve the efficiency of a Cu-based Fenton-like reaction. Resultantly, this nanosystem featuring Fenton-like activity, GSH consumption, H₂O₂ self-sufficiency and chemotherapy exhibits a great antitumor effect with a tumor inhibition ratio of 93.05%. Overall, this study provides a promising strategy to enhance CDT for effective tumor therapy.

In recent years, poly(vinylidene fluoride) (PVDF) has emerged as a versatile polymer with a wide range of applications across various fields. PVDF's piezosensitivity, versatility, crystalline structure, and tunable parameters have established it as a highly sought-after material. Furthermore, PVDF and its copolymers exhibit excellent processability and chemical resistance to a diverse array of substances. Of particular significance is its remarkable structural stability in physiological media, which highlights its potential for use in the development of biomedical products. This review offers a comprehensive overview of the latest advancements in PVDF-based biomedical systems. It examines the fabrication of stimulus-responsive delivery systems, bioelectric therapy devices, and tissue-regenerating scaffolds, all of which harness the piezosensitivity of PVDF. Moreover, the potential of PVDF in the fabrication of both invasive and non-invasive diagnostic tools is investigated, with particular emphasis on its flexibility, transparency, and piezoelectric efficiency. The material's high biocompatibility and physiological stability are of paramount importance in the development of implantable sensors for long-term health monitoring, which is crucial for the management of chronic diseases and postoperative care. Additionally, we discuss a novel approach to photoacoustic microscopy that employs a PVDF sensor, thereby eliminating the necessity for external contrast agents. This technique provides a new avenue for non-invasive imaging in biomedical applications. Finally, we explore the challenges and prospects for the development of PVDF-based systems for a range of biomedical applications. This review is distinctive in comparison to other reviews on PVDF due to its concentrated examination of biomedical applications, including pioneering imaging techniques, long-term health monitoring, and a detailed account of advancements in the field. Collectively, these elements illustrate the potential of PVDF to markedly influence biomedical engineering and patient care, distinguishing it from existing literature. By leveraging the distinctive attributes of PVDF and its copolymers, researchers can continue to advance the frontiers of biomedical engineering, with the potential to transform patient care and treatment outcomes.

A major risk associated with surgery, including bone tissue procedures, is surgical site infection. It is one of the most common as well as the most serious complications of modern surgery. A helpful countermeasure against infection is antibiotic therapy. In the present study, a methodology has been developed to obtain clindamycin-modified polymer–ceramic hybrid composite coatings for potential use in bone regenerative therapy. The coatings were prepared using a UV-light photocrosslinking method, and the drug was bound to a polymeric and/or ceramic phase. The sorption capacity of the materials in PBS was evaluated by determining the swelling ability and equilibrium swelling. The influence of the presence of ceramics on the amount of liquid bound was demonstrated. The results were correlated with the rate of drug release measured by high-performance liquid chromatography (HPLC). Coatings with higher sorption capacity released the drug more rapidly. Scanning electron microscopy (SEM) imaging was carried out comparing the surface area of the coatings before and after immersion in PBS, and the proportions of the various elements were also determined using the EDS technique. Changes in surface waviness were observed, and chlorine ions were also determined in the samples before incubation. This proves the presence of the drug in the material. The in vitro tests conducted indicated the release of the drug from the biomaterials. The antimicrobial efficacy of the coatings was tested against Staphylococcus aureus. The most promising material was tested for cytocompatibility (MTT reduction assay) against the mouse fibroblast cell line L929 as well as human osteoblast cells hFOB. It was demonstrated that the coating did not exhibit cytotoxicity. Overall, the results signaled the potential use of the developed polymer–ceramic hybrid coatings as drug carriers for the controlled delivery of clindamycin in bone applications. The studies conducted were the basis for directing samples for further in vivo experiments determining clinical efficacy.

Bacterial keratitis is a common form of inflammation caused by the bacterial invasion of the corneal stroma after trauma. In extreme cases, it can lead to severe visual impairment or even blindness; therefore, timely medical intervention is imperative. Unfortunately, widespread misuse of antibiotics has led to the development of drug resistance. In recent years, organ-on-chips that integrate multiple cell co-cultures have extensive applications in fundamental research and drug screening. In this study, immortalized human corneal epithelial cells and primary human corneal fibroblasts were co-cultured on a porous polydimethylsiloxane membrane to create a cornea-on-a-chip model. The developed multilayer epithelium closely mimicked clinical conditions, demonstrating high structural resemblance and repeatability. By introducing a consistently defective epithelium and bacterial infection using the space-occupying method, we successfully established an in vitro model of bacterial keratitis using S. aureus. We validate this model by evaluating the efficacy of antibiotics, such as levofloxacin, tobramycin, and chloramphenicol, through simultaneously observing the reactions of bacteria and the two cell types to these antibiotics. Our study has revealed the barrier function of epithelium of the model and differentiated efficacy of three drugs in terms of bactericidal activity, reducing cellular apoptosis, and mitigating scar formation. Altogether, the cornea on chip enables the assessment of ocular antibiotics, distinguishing the impact on corneal cells and structural integrity. This study introduced a biomimetic in vitro disease model to evaluate drug efficacy and provided significant insights into the extensive effects of antibiotics on diverse cell populations within the cornea.

Confocal reflectance imaging typically suffers from high background and poor sensitivity. We demonstrate sensitive and low-background reflectance imaging of cells encapsulated in transparent 3D hydrogels. Nanoscale cell morphology is visualized with sensitivity similar to confocal fluorescence, with low laser power, minimal specimen preparation, and reduced toxicity.

Accurate tumor detection is crucial for the early discovery and subsequent treatment of small neoplastic foci. Molecular imaging, which combines non-invasiveness, high specificity, and strong sensitivity, excels in diagnosing early tumors and stands out among tumor diagnosis methods. Here, we introduced a dual-modal imaging probe capable of actively targeting tumor cells, suitable for both near-infrared (NIR) fluorescence and magnetic resonance imaging (MRI). Dendritic mesoporous silica was used as a carrier for the probe, encapsulating Ag₂S quantum dots (QDs) for NIR fluorescence imaging. Additionally, the probe conjugated the MRI contrast agent Gd-DOTA and cetuximab, which targeted EGFR on the tumor cell membrane surface, to achieve dual-modal imaging in the tumor area. This strategy provided a methodology for the accurate diagnosis of early-stage tumor lesions and guides precise lesion resection during surgery, offering significant potential for clinical application.

Due to their rapid spread, high variability, and drug-resistant strains, new viral infections are continuously emerging. A lack of effective antiviral drugs and vaccines, resulting in disease and death, has significant socioeconomic consequences. Hemoperfusion can effectively adsorb and remove toxins from the blood, thus purifying the blood and serving as an acute treatment. Therefore, the aim of this study was to construct adsorbents to selectively remove viruses from the blood to quickly treat pathogen infection. We reported on new metal–organic framework (MOF)-polymer beads based on MIL-53(Al) and cellulose acetate (CNC), which were prepared by a one-step phase inversion method and applied as a viral hemo-adsorbent for the first time. The characterization results demonstrated that MIL-53(Al) was well dispersed in the CNC matrix. The adsorption results demonstrated that the capture efficiency of the human immunodeficiency virus (HIV) could exceed 99.93%, and the corresponding infectious titer decreased by approximately 10³ times in clinical application. Moreover, CNC/MIL-53 exhibited low hemolysis ratios and good anticoagulant properties. Furthermore, molecular dynamics simulations revealed that the interplay of hydrogen bonding was the governing physisorption mechanism. Overall, CNC/MIL-53 could serve as a new type of hemoperfusion adsorbent for virus removal from blood and provide a new treatment pathway to mitigate epidemics.