ACS Biomaterials Science & Engineering最新文献

IgA nephropathy (IgAN) is a primary glomerulonephritis mediated by autoimmunity, characterized by an abnormal increase and the deposition of IgA in the glomeruli. In recent years, most studies have emphasized the crucial role of the gut-kidney axis in the pathogenesis of IgA nephropathy, and the ileal Peyer patches in the intestinal mucosal immune system are the main site for IgA production. Therefore, in this study, hydroxychloroquine (HCQ) and dexamethasone (DXM) were used as model drugs, and yeast cell wall (YCW)-coated oleic acid-grafted chitosan (CSO) was used as a carrier to construct a yeast cell wall oral drug delivery system HCQ/DXM@CSO@YCW. This delivery system achieves ileal targeted delivery through the yeast cell wall (YCW), reduces IgA production, and synergistically regulates the inflammatory pathological environment. The delivery system had good gastrointestinal stability and biocompatibility. In vitro cell experiments had shown the targeted uptake ability of dendritic cells and macrophages, and in vitro intestinal experiments showed that the YCW has ileal targeting properties. In vivo pharmacodynamic experiments showed that the HCQ/DXM@CSO@YCW delivery system could significantly reduce the serum IgA levels and IgA deposition in the renal tissue of IgAN mice, as well as the levels of IL-6, TNF-α, and TGF-β in the renal tissue, improving the pathological morphology of the renal tissue. Therefore, the DXM/HCQ@CSO@YCW oral administration system provided a new intestinal targeted delivery platform for intestinal mucosal immunotherapy in IgA nephropathy.

Nanofiber (NF) membranes have demonstrated considerable potential in cellular transmigration studies due to their resemblance to the biophysical properties of basement membranes, enabling cellular behaviors that closely mimic those observed in vivo. Despite their advantages, conventional NF membranes often encounter issues in transmigration assays due to their transparency, which leads to overlapping fluorescent signals from transmigrated and nontransmigrated cells. This overlap complicates the clear differentiation between these cell populations, making the quantitative evaluation of live-cell transmigration challenging. To address this issue, we developed a light-blocking nanofiber (LB-NF) membrane by incorporating carbon black into polycaprolactone NFs. This LB-NF membrane is designed not only to mimic the biophysical properties of the basement membrane but also to enable in situ analysis of transmigrated cells through its light-blocking properties. Our study demonstrated the effectiveness of the LB-NF membrane in a transmigration assay using human brain cerebral microvascular endothelial cells (HBEC-5i), enabling physiologically relevant cell transmigration while significantly enhancing the accuracy of in situ fluorescence detection. Furthermore, drug testing within a choroidal neovascularization model using the LB-NF membrane underscores its utility and potential impact on pharmaceutical development, particularly for diseases involving abnormal cell transmigration. Therefore, the developed LB-NF membrane represents a valuable tool for the precise assessment of in situ cellular transmigration and holds significant promise for advancing drug screening and therapeutic development.

Cisplatin (CDDP) is one of the most commonly used chemotherapeutic agents for solid tumors and hematologic malignancy. However, its therapeutic outcomes have remained unsatisfactory due to severe side effects, a short elimination half-life, the emergence of drug resistance, and the induction of metastasis. Combination with other chemotherapeutic agents has been proposed as one strategy to address the drawbacks of CDDP-based therapy. Therefore, this study aimed to boost the antitumor efficacy of cisplatin (CDDP) with a PI3K/mTOR dual inhibitor, dactolisib (BEZ), via a carrier-free codelivery system based on the self-assembly of the coordinated CDDP-BEZ. The synthesized CDDP-BEZ nanoparticles (NPs) possess sensitive pH-responsiveness, facilitating the delivery of both drugs to cancer cells. CDDP-BEZ NPs specifically enhanced cytotoxicity in cancer cells due to the synergy between cisplatin and dactolisib, resulting in augmented DNA damage, activation of mitochondria-dependent apoptosis, and increased inhibition on the PI3K/mTOR signaling axis. The inhibition of tumor migration and metastasis by CDDP-BEZ NPs was observed both in vitro and in vivo. Our data suggest that CDDP-BEZ NPs could serve as a safe and effective platform to maximize the synergy between both drugs in combating cancer, presenting a strategy to promote the therapeutic efficacy of platinum-based chemotherapeutic agents by combining them with PI3K inhibitors.

The advancement of in vitro engineered cardiac tissue-based patches is paramount for providing viable solutions for restoring cardiac function through in vivo implantation. Numerous techniques described in the literature aim to provide diverse mechanical and topographical cues simultaneously, fostering enhanced in vitro cardiac maturation and functionality. Among these, cellulose paper-based scaffolds have gained attention owing to their inherent benefits, such as biocompatibility and ease of chemical and physical modification. This study introduces a novel approach of utilizing customized paper-based scaffolds as cell culture substrates, facilitating both the formation and manipulation of cell constructs while promoting mechanical contraction. Here, we investigated two methodologies to foster mechanical contractions of paper-based constructs: the incorporation of micropatterns on paper to dictate cell orientation and macropattern created by the origami-folded paper. Both approaches provide mechanical support and foster cardiac functionality. However, while micropatterning does not significantly improve the functional parameters, a macropattern created by origami folding proves to be essential in facilitating contraction of the paper-based cardiac constructs. Furthermore, we provide proof of principle for the combination with a layer of physiologically differentiated microvascular networks. This approach holds great promise for the development of structurally organized contractile cardiac tissues with the possibility of creating multistrata of cardiac and vascular layers to promote in vivo cell survival and function beyond what is typically achieved in conventional cell culture.

The rapid increase in the number of stimuli-responsive polymers, also known as smart polymers, has significantly advanced their applications in various fields. These polymers can respond to multiple stimuli, such as temperature, pH, solvent, ionic strength, light, and electrical and magnetic fields, making them highly valuable in both the academic and industrial sectors. Recent studies have focused on developing hydrogels with self-healing properties that can autonomously recover their structural integrity and mechanical properties after damage. These hydrogels, formed through dynamic covalent reactions, exhibit superior biocompatibility, mechanical strength, and responsiveness to stimuli, particularly pH changes. However, conventional hydrogels are limited by their weak and brittle nature. To address this, ionizable moieties within polyelectrolytes can be tuned to create ionically cross-linked hydrogels, leveraging natural polymers such as alginate, chitosan, hyaluronic acid, and cellulose. The integration of ionic liquids into these hydrogels enhances their mechanical properties and conductivity, positioning them as significant self-healing agents. This review focuses on the emerging field of stimuli-responsive ionic-based hydrogels and explores their potential in dermal applications and tissue engineering.

Matrix stiffness is a key factor in breast cancer progression, but its impact on cell function and response to treatment is not fully understood. Here, we developed a stiffness-tunable hydrogel-based three-dimensional system that recapitulates the extracellular matrix and physiological properties of human breast cancer in vitro. Adjusting the ratio of GelMA to PEGDA in the hydrogel formulation enabled the fine-tuning of matrix stiffness across a range of 7 to 52 kPa. Utilizing this three-dimensional (3D) hydrogel platform for a breast cancer cell culture has enabled precise functional evaluations. Variations in matrix stiffness resulted in significant changes in the morphology of breast cancer cells after 2 weeks of incubation. The analysis of transcriptomic sequencing revealed that the 3D microenvironment significantly changed the expression of a wide panel of transcriptomic profiles of breast cancer cells in various matrix stiffness. Gene Ontology analysis further suggested that specific biological functions could potentially be linked to the magnitude of the matrix stiffness. According to our findings, extracellular matrix rigidity modulates the sensitivity of breast cancer cells to paclitaxel and adriamycin. Notably, the expression of ABCB1 and YAP1 genes may be upregulated in the 3D culture environment, potentially contributing to the increased drug resistance observed in breast cancer cells. This work aims to establish facile adjustable hydrogels to deepen insights into matrix rigidity effects on breast cancer cells within 3D microenvironments, highlighting the critical role of extracellular matrix stiffness in modulating cell-matrix interactions.

Acute renal injury (AKI) has a high incidence rate and mortality, but current treatment methods are limited. As a kind of nanomaterial with enzyme-like activity, nanozyme has shown outstanding advantages in treating AKI according to recent reports. Herein, we assess the potential of manganese-based nanozymes (MnO₂-BSA NPs) with excellent biosafety in effectively alleviating AKI. Our findings in vitro and in vivo reveal that MnO₂-BSA NPs exert regulatory effects on oxidative stress, inflammation, and apoptosis. These effects are mediated through activation of the Nrf2/HO-1 and PI3K/Akt/NF-κB pathways. Notably, it was observed that the cytoprotective effect of MnO₂-BSA NPs is abrogated upon inhibition of Nrf2 expression, highlighting the important role of this transcription factor in cellular protection. In summary, the study demonstrates the protective effect of MnO₂-BSA NPs in AKI and provides the molecular mechanisms involved, which can contribute to the advancement of potential therapeutic interventions for nanozyme-based treatments.

Oral health problems, particularly tooth defects, can significantly affect people's quality of life and overall well-being. The development of titanium (Ti) dental implants has largely replaced natural tooth roots to prevent periodontal and gastrointestinal diseases. However, challenges such as postoperative bacterial infections and poor osseointegration continue to hinder progress in dental implant technology. To tackle these issues, we used hydroxypropyl trimethylammonium chloride chitosan (HACC) and gallic acid-modified gelatin (GAG) to create extracellular matrix (ECM) coatings on titanium using layer-by-layer self-assembly. GAG showed better water solubility at room temperature, being over 99.0 times more soluble than regular gelatin. In vivo and in vitro analyses of the ECM coatings revealed their antibacterial properties and their ability to promote osteogenic differentiation, resulting in over 31.5 times more calcareous deposits than Ti. This strategy shows potential for improving oral health and reducing the complications associated with dental implants in clinical settings.

Due to the intense demand for low-cost, environmentally friendly, and stable uric acid (UA) detection methods, a novel biosensing nanosystem made with marine diatom was studied. Reduced by live diatom (Thalassiosira pseudonana), metallic nanoparticles (Cu_X) were hybridized with the heteronanostructure (Diatom frustule, DF), showing peroxidase activity 2.66-fold over horseradish peroxidase (HRP). To immobilize the enzyme directionally with increasing loading amounts, silaffin peptides (R₅ and T₈) were designed for tagging the urate oxidase (UoX). The enzyme loading on DF of tagged UoX was 1.76-fold (R₅) and 1.54-fold (T₈) that of untagged UoX. The activity of immobilized UoX-R₅ was 5.29-11.76-fold more than that of free UoX-R₅ at various pH levels (5-10) and temperatures (20-60 °C). The nanosystem (UoX-R₅ immobilized on Cu_X-coated diatom frustules, termed as BioHNS) demonstrated a superior linear range of 5 × 10^-6 to 1 × 10^-3 M and a detection limit of 1.6 μM, surpassing the performance of the majority of reported UA sensors. The recoveries of UA in urine were detected by the BioHNS, ranging from 96.93 to 105.35%, with a relative deviation of less than 5.00%. The BioHNS showed excellent anti-interference and storage stability (2 months). In summary, BioHNS demonstrates significant potential as a sustainable and environmentally friendly biosensor for uric acid detection, highlighting its substantial relevance to the biomedical applications of marine diatoms.

Bioprinting creates 3D tissue models by depositing cells encapsulated in biocompatible materials. These 3D printed models can better emulate physiological conditions in comparison with traditional 2D cell cultures or animal models. Such models can be produced from human cells, possessing human genetics and replicating the 3D microenvironment found in vivo. Many different types of biocompatible materials serve as bioinks, including gelatin methacryloyl (GelMA), alginate, fibrin, and gelatin. Nanocellulose has emerged as a promising addition to these materials. Nanocellulose─composed of cellulose chain bundles with lateral dimensions ranging from a few to several tens of nanometers─possesses key properties for 3D bioprinting applications. It can form biocompatible hydrogels, which have excellent physical properties, and its structure resembles collagen, making it useful for modeling tissues with high collagen content such as bone, cartilage, sink, and muscle. Here we review some of the recent advances in the use of nanocellulose in bioinks for the creation of bone, cartilage, skin, and muscle tissue specific models and identify areas for future progress.