Biomaterials Science最新文献

Gemcitabine (GEM) is a first line chemotherapy drug for bladder cancer (BCa). GEM's lack of specificity has led to disadvantages, resulting in low efficiency, especially when combined with the targeted treatment of BCa stem cells (CSCs), which is considered the cause of BCa recurrence and progression. To enhance the anti-cancer effect and reduce the side effects of GEM targeting of BCa cells/CSCs, an aptamer drug conjugate (ApDC) targeted delivery system was used to improve the efficiency of GEM in BCa therapy using EpCAM aptamer-GEM conjugates based on the epithelial cell adhesion molecule (EpCAM), which is highly expressed on the cell membrane of BCa cells/CSCs. We designed and synthesized EpCAM aptamer gemcitabine conjugates (EpCAM-GEMs, one aptamer carried three GEMs). The targeting effect of EpCAM-GEMs was examined in a xenograft model using an in vivo imaging system. To evaluate the antitumor activity and mechanism of EpCAM-GEMs, Cell Counting Kit-8, apoptosis and colony formation assays; BCa CSC xenotransplantation; xenotransplantation of subcutaneous tumors; a lung metastasis model; an in situ model; and biosafety assessment were used in vitro and in vivo. EpCAM is highly expressed on the surface of BCa cells/CSCs. EpCAM-GEMs were automatically synthesized using a DNA synthesizer, were stable in serum, and selectively delivered GEM to kill BCa cells/CSCs. EpCAM-GEMs entered BCa cells via macropinocytosis, released GEM to inhibit DNA synthesis, and degraded all BCa cells under the action of a BCa cell intracellular phosphatase; however, they did not kill normal cells because of their low EpCAM expression. EpCAM-GEMs inhibited BCa growth and metastasis in three bladder tumor models, with good biosafety. These results demonstrated the targeted anti-tumor efficiency and good biosafety of EpCAM-GEMs in BCa treatment, which will provide a new therapeutic strategy in BCa biomarker targeted therapy.

Thrombosis, a major cause of morbidity and mortality worldwide, presents a complex challenge in cardiovascular medicine due to the intricacy of clotting mechanisms in living organisms. Traditional research approaches, including clinical studies and animal models, often yield conflicting results due to the inability to control variables in these complex systems, highlighting the need for more precise investigative tools. This review explores the evolution of in vitro thrombosis models, from conventional polydimethylsiloxane (PDMS)-based microfluidic devices to advanced hydrogel-based systems and cutting-edge 3D bioprinted vascular constructs. We discuss how these emerging technologies, particularly vessel-on-a-chip platforms, are enabling researchers to control previously unmanageable factors, thereby offering unprecedented opportunities to pinpoint specific clotting mechanisms. While PDMS-based devices offer optical transparency and fabrication ease, their inherent limitations, including non-physiological rigidity and surface properties, have driven the development of hydrogel-based systems that better mimic the extracellular matrix of blood vessels. The integration of microfluidics with biomimetic materials and tissue engineering approaches has led to the development of sophisticated models capable of simulating patient-specific vascular geometries, flow dynamics, and cellular interactions under highly controlled conditions. The advent of 3D bioprinting further enables the creation of complex, multi-layered vascular structures with precise spatial control over geometry and cellular composition. Despite significant progress, challenges remain in achieving long-term stability, incorporating immune components, and translating these models to clinical applications. By providing a comprehensive overview of current advancements and future prospects, this review aims to stimulate further innovation in thrombosis research and accelerate the development of more effective, personalized approaches to thrombosis prevention and treatment.

An increase in plastic waste and its release into the environment has led to health concerns over microplastics (MPs) in the environment. The intestinal mucosal layer is a key defense mechanism against ingested MPs, preventing the migration of particles to other parts of the body. MP migration through intestinal mucus is challenging to study due to difficulties in obtaining intact mucus layers for testing and numerous formulations, shapes, and sizes of microplastics. Previous studies have primarily used mucus from animals, hydrogel models, and mucus samples from other parts of the body as substitutes. This study examines how different MP compositions, sizes (40–500 nm), and surface functionalizations alter MP migration through human intestinal mucus; how the mucus layer protects cells from MP uptake, toxicity, and inflammation; and how the intestinal mucus prevents the migration of other environmental toxins via MP particles. The presence of a mucus layer also provides critical protection against cytotoxicity, reactive oxygen species production, and uptake for all particles tested, although certain functionalizations, such as streptavidin, are particularly harmful to cells with high toxicity and inflammation. Understanding the properties that assist of impede the diffusion of MPs through mucus is relevant to the overall bioaccumulation and health effects of MPs as well as drug delivery purposes.

Metallic biomaterials are extensively used in orthopedics and dentistry, either as implants or coatings. In both cases, metal ions come into contact with surrounding tissues causing a particular cell response. Here, we present a biofabricated in vitro tissue model, consisting of a hydrogel reinforced with a melt electrowritten mesh, to study the effects of bound and released metal ions on surrounding cells embedded in a hydrogel matrix. We evaluate the biocompatibility, bioactivity, and antibacterial properties of these metal coatings. Our approach involves integrating physical vapour deposition coating technology with 3D bioprinting methods. To produce tissue models, melt electrowritten (MEW) meshes composed of polycaprolactone (PCL) were printed and integrated into cell-laden methacrylated galatin (GelMa). The mouse embryonic fibroblast cell line (NIH3T3) was used. GelMa concentration and printing parameters for MEW were adjusted and mechanical analysis of the models was performed to find the optimal material composition. Optimized models were placed on the glass slide surfaces coated with typically non-toxic metals, i.e. titanium (Ti), tantalum (Ta), zirconium (Zr), silver (Ag), tungsten (W), and niobium (Nb). Except for W, all other coatings were stable in a physiological wet environment, as studied by SEM. The viability of the cells at different distances from the coated surface was analyzed. Antibacterial tests against pathogens Staphylococcus aureus and Escherichia coli were used to assess the models’ resistance, important for infection control. While Ag coatings showed toxicity, Nb, Ta, Ti, and Zr coatings promoted fibroblast growth, with the highest cell viability after 14 days of culture revealed for Ta and Nb. The strongest antimicrobial effect against E. coli and S. aureus was observed for Ag and W, while Ta exhibited antibacterial activity only against S. aureus. From a broader perspective, our work offers an effective 3D in vitro model for an in-depth characterization of the biocompatibility of metals and metal coatings.

The pivotal roles played by nitric oxide (NO) in tissue repair, inflammation, and immune response have spurred the development of a wide range of NO-releasing biomaterials. More recently, 3D printing techniques have significantly broadened the potential applications of polymeric biomaterials in biomedicine. In this context, the development of NO-releasing biomaterials that can be fabricated through 3D printing techniques has emerged as a promising strategy for harnessing the benefits of localized NO release from implantable devices, tissue regeneration scaffolds, or bandages for topical applications. Although 3D printing techniques allow for the creation of polymeric constructs with versatile designs and high geometric precision, integrating NO-releasing functional groups or molecules into these constructs poses several challenges. NO donors, such as S-nitrosothiols (RSNOs) or diazeniumdiolates (NONOates), may release NO thermally, complicating their incorporation into resins that require heating for extrusion-based 3D printing. Conversely, NO released photochemically from RSNOs effectively inhibits radical propagation, thus hindering photoinduced 3D printing processes. This review outlines the primary strategies employed to overcome these challenges in developing NO-releasing biomaterials via 3D printing, and explores future prospects in this rapidly evolving field.

Incorporation of polyethylene glycol (PEG) is widely used in lipid nanoparticle (LNP) formulation in order to achieve adequate stability due to its stealth properties. However, studies have detected the presence of anti-PEG neutralizing antibodies after PEGylated LNP treatment, which are associated with anaphylaxis, accelerated LNP clearance and premature release of cargo. Here, we report the development of LNPs incorporating ganglioside, a naturally occurring stealth lipid, as a PEG-free alternative. Physicochemical characterization showed that ganglioside-LNPs exhibited superior stability throughout prolonged cold storage compared to stealth-free LNPs, preventing particle aggregation. Additionally, there was no significant change in particle size after serum incubation, indicating the ability of ganglioside to prevent unwanted serum protein adsorption. These results exemplify the effective stealth properties of ganglioside. Furthermore, ganglioside-LNPs exhibited significantly higher mRNA transfection in vivo after intravenous administration compared to stealth-free LNPs. The ability of ganglioside to confer excellent stealth properties to LNPs while still enabling in vivo mRNA expression makes it a promising candidate as a natural substitute for immunogenic PEG in mRNA-LNP delivery platforms, contributing to the future advancement of gene therapy.

Infected alveolar bone defects pose challenging clinical issues due to disrupted intrinsic healing mechanisms. Thus, the employment of advanced biomaterials enabling the modulation of several aspects of bone regeneration is necessary. This study investigated the effect of multi-functional nanoparticles on anti-inflammatory/osteoconductive characteristics and bone repair in the context of inflamed bone abnormalities. Tannic-acid mineral nanoparticles (TMPs) were prepared by the supramolecular assembly of tannic acid with bioactive calcium and phosphate ions, which were subsequently incorporated into collagen plugs via molecular interactions. Under physiological conditions, in vitro analysis confirmed that tannic acid was dissociated and released, which significantly reduced the expression of pro-inflammatory genes in lipopolysaccharide (LPS)-activated RAW264.7 cells. Meanwhile, the bioactive ions of Ca²⁺ and PO₄³⁻ synergistically increased the gene and protein expressions of osteogenic markers of bone marrow-derived stem cells. For in vivo studies, combined endodontic-periodontal lesions were induced in beagle dogs where the plugs were readily implanted. After 2 months of the implantation, analysis of micro-computed tomography and histomorphometry revealed that groups of dogs implanted with the plug incorporating TMPs exhibited a significant decrease in bone surface density as well as structural model index, and significant increase in the mineralized bone content, respectively, with positive OPN expression being observed in reversal lines. Notably, the profound improvement in bone regeneration relied on the concentration of TMPs in the implants, underscoring the promise of multi-functional nanoparticles for treating infected alveolar bones.

Biphasic calcium phosphate (BCP) is a bioceramic widely used in hard tissue engineering for bone replacement. BCP consists of β-tricalcium phosphate (β-TCP) – a highly soluble and resorbable phase – and hydroxyapatite (HA) – a highly stable phase, creating a balance between solubility and resorption, optimally supporting cell interactions and tissue growth. The β-TCP/HA ratio significantly affects the resorption, solubility, and cellular response, with a higher β-TCP ratio increasing resorption due to its solubility. BCP is commonly synthesized by calcining calcium-deficient apatite (CDA) at temperatures above 700 °C via direct or indirect methods. This study investigated the effects of pH and sintering temperature on BCP synthesized via wet precipitation, aiming to achieve an 80/20 β-TCP/HA ratio, which is known to be optimal for bone regeneration. By maintaining a constant Ca/P precursor ratio of 1.533, the optimal conditions were determined to be a pH of 5.5–6 and a sintering temperature of 900 °C, chosen to balance material stability and solubility. The successful synthesis was confirmed using X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. At the same time, the material's physical and chemical properties were further characterized through scanning electron microscopy (SEM) and degradation studies in a simulated body fluid (SBF). In vitro tests demonstrated excellent cytocompatibility and osteogenic differentiation, while in vivo studies on rabbit femur defects demonstrated significant bone regeneration, with bone-to-tissue volume ratios exceeding 50% within four weeks. These results highlight the potential of BCPs in bone tissue engineering and biomaterials research.

Nature-inspired superhydrophobic materials have attracted considerable interest in blood-contacting biomedical applications due to their remarkable water-repellent and self-cleaning properties. However, the interaction mechanism between blood components and superhydrophobic surfaces remains unclear. To explore the effect of trapped air on platelet adhesion, we designed four distinct hydrophobic titanium dioxide (TiO₂) nanostructures with different fractions of trapped air. Ultrasonication was used to remove trapped air, allowing for direct comparison between hydrophobic surfaces with and without observable trapped air. The results demonstrate that all four kinds of hydrophobic materials significantly reduce platelet adhesion, regardless of observable trapped air. As nanostructure size increases, the proportion of air also increases, trapped air reduces fibrinogen adsorption but increases platelet adhesion, particularly in the largest nanostructures with superhydrophobicity. Upon air removal, protein adsorption increases compared to the same sample with air, while platelet adhesion decreases. This indicates that trapped air reduces protein adsorption but unexpectedly enhances platelet adhesion, which is contrary to our intuitive expectations. Conversely, hydrophobic surfaces without trapped air minimize platelet adhesion. To gain a better understanding of this phenomenon, we propose an interpretable model. Overall, this study challenges conventional assumptions and offers new insights for the design and application of superhydrophobic materials.

The application of nanotechnology in medical biology has seen a significant rise in recent years because of the introduction of novel tools that include supramolecular systems, complexes, and composites. Dendrimers are one of the remarkable examples of such tools. These spherical, regularly branching structures with enhanced cell compatibility and bioavailability have shown to be an excellent option for gene or drug administration. They are the fourth important architectural group of polymers after the three well-known types (branched, cross-linked, and linear polymers). These tiny macromolecules generate nanometer-size structures consisting of branching, with identical units assembled around a central core. By regulating dendrimer synthesis, it is possible to manipulate both their molecular weight and chemical content carefully, permitting predictable tailoring of their biocompatibility and pharmacokinetics, making them a promising candidate for biomedical uses. In contrast to their more easily obtainable synthetic techniques and comparable functions in hyperbranched polymers, dendrimers have demonstrated efficacy in biological applications, exhibiting remarkable sample purity and synthesizing reproducibility. Dendrimers are appealing as basic materials for manufacturing nanomaterials for uses in many different disciplines because of their highly specified chemical structure and globular form. Thus, much effort has been made to create functional materials with dendrimers. Especially looking at dendrimer-based nanomaterials meant for use in the biomedical domain, this review discusses the design, types, properties, and function of bionanomaterials employing several techniques, including surface modification, assembly, and hybrid development, and their uses.