ACS Applied Bio Materials最新文献

Stereolithography (SLA) 3D printing is a rapid prototyping technique and reproducible manufacturing platform, which makes it a useful tool to develop advanced microfluidic devices for bioanalytical applications. However, limited information exists regarding the physical, chemical, and biological properties of the photocured polymers printed with SLA. This study demonstrates the characterization of a commercially available SLA 3D printed polymer to evaluate the potential presence of any time-dependent changes in material properties that may affect its ability to produce functional, capillary-action microfluidic devices. The printed polymer was analyzed with Fourier transform infrared-attenuated total reflectance, contact angle measurements, tensile test, impact test, scanning electron microscopy, and fluid flow analysis. Polymer biocompatibility was assessed with propidium iodide flow cytometry and an MTT assay for cell viability. The material characterization and biocompatibility results were then implemented to design and fabricate a self-driven capillary action microfluidic device for future use as a bioanalytical assay. This study demonstrates temporally stable mechanical properties and biocompatibility of the SLA polymer. However, surface characterization through contact angle measurements shows the polymer's wettability changes over time which indicates there is a limited postprinting period when the polymer can be used for capillary-based fluid flow. Overall, this study demonstrates the feasibility of implementing SLA as a high-throughput manufacturing method for capillary action microfluidic devices.

Lipid droplets (LD) are crucial in pathological processes or conditions associated with abnormal lipid metabolism, such as obesity, diabetes, atherosclerosis, fatty liver diseases, and cancers. Cancer cells frequently contain elevated levels of nonpolar lipid droplets (LDs), serving as energy reserves. The proliferation of LDs, accompanied by an increase in viscosity, is a characteristic feature of cancer cells that prompted us to devise a fluorescent sensor for LD detection at physiological pH. However, developing fluorescent LD-specific probes with high polarity sensitivity and deep tissue/cell imaging capability remains challenging. Therefore, we present a TICT probe with strong solvatochromism, superior response to viscosity, microenvironment sensitivity, and a large Stokes shift. Additionally, it offers numerous advantages, including high sensitivity, specificity, high fluorescence quantum yield, and remarkable spatial resolution, which enables precise monitoring of lipid droplets (LD). Thus, this probe can effectively monitor alterations in viscosity and polarity of lipid droplet expression in live cells, thereby offering the potential for visualizing physiological abnormalities or pathological conditions. The probe offers excellent lipid droplet targeting and also sensitively monitors the oleic-acid-mediated lipid droplet accumulation and immunosuppressant/inflammatory drugs in HeLa cells.

MXenes are among the most diverse and prominent 2D materials. They are being explored in almost every field of science and technology, including biomedicine. In particular, they are being investigated for photothermal therapy, drug delivery, medical imaging, biosensing, tissue engineering, blood dialysis, and antibacterial coatings. Despite their proven biocompatibility and low cytotoxicity, their genotoxicity has not been addressed. To investigate whether MXenes interfere with DNA integrity in cultured cells, we loaded the cells with MXenes and examined the fragmentation of their chromosomal DNA by a DNA comet assay. The presence of both Ti₃C₂T_x and Nb₄C₃T_x MXenes generated DNA comets, suggesting a strong genotoxic effect in murine melanoma and human fibroblast cells. However, no corresponding cytotoxicity was observed, confirming that MXenes were well tolerated by the cells. The lateral size of the MXene flakes was critical for developing the DNA comets; submicrometer flakes induced the DNA comets, while larger flakes did not. MXenes did not induce DNA comets in dead cells. Moreover, the extraction of the chromosomal DNA from the MXene-loaded cells or mixing the purified DNA with MXenes showed no signs of DNA fragmentation. Unconstrained living MXene-loaded cells did not show cleavage of the DNA with MXenes under electrophoresis conditions. Thus, the DNA comet assay showed the ability of submicrometer MXene particles to penetrate living cells and induce DNA fragmentation under the applied field. The most probable mechanism of DNA comet formation is the rotation and movement of submicrometer MXene flakes inside cells in an electric field, leading to cleavage and DNA shredding by MXene's razor-sharp edges. Under all other conditions of interest, titanium- and niobium-carbide-based MXenes showed excellent biocompatibility and no signs of cytotoxicity or genotoxicity. These findings may contribute to the development of strategies for cancer therapy.

Creatinine is indeed a crucial biomarker for kidney diseases. In this work, a novel electrochemical biosensor based on a copper-hemin metal organic framework [Cu-hemin metal-organic framework (MOF)] nanoflake decorated with palladium (Pd) (Pd/Cu-hemin MOF) was fabricated and incorporated with creatinine deiminase (CD) on a glassy carbon electrode (GCE) for creatinine detection. The formation of a Pd/Cu-hemin MOF composite was confirmed by X-ray photoelectron spectroscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. The formation of the composite as nanoflakes is evident from the scanning electron microscopy image. The transmission electron microscopy image clarifies the decoration of palladium nanoparticles on Cu-hemin MOF surfaces. Thus, the proposed biosensor (Pd/Cu-hemin MOF/CD/GCE) electrochemical performances were studied with cyclic voltammetry, differential pulse voltammetry, and electrochemical impedance spectroscopy. As a result, the Pd/Cu-hemin MOF/CD/GCE-based electrochemical detection of creatinine exhibits a broad linear range from 0 to 130 μM (R² = 0.99), a low limit of detection 0.08 μM, and an excellent sensitivity of 3.2 μA μM^-1 cm^-2. The biosensor also determines creatinine in samples of human urine with a good recovery from 99.4 to 100.8%. Thus, in this study, an electrochemical biosensing platform based on Pd/Cu-hemin MOF/CD/GCE has been designed practically for creatinine.

Photodynamic therapy has advantages of high selectivity, less invasiveness, and high lethality for cancer cells compared with traditional treatment methods. However, some problems have hindered the development of photodynamic therapy, such as limited penetration depth, lack of oxygen, and toxicity. Carbon dots are widely used in the imaging and treatment of tumors due to their excellent optical and physicochemical properties, so effective methods have been explored to address the issues in photodynamic therapy via carbon dots. This review aims to elucidate the role of carbon dots in photodynamic therapy of cancer. Moreover, we summarize and discuss some strategies to harness carbon dots to enhance photodynamic therapy. Finally, we summarize many cancer synergistic therapeutic modalities involving carbon dots such as chemodynamic therapy, photothermal therapy, and immunotherapy in combination with photodynamic therapy to achieve more effective and safer treatments.

Nucleic acid detection is important in a wide range of applications, including disease diagnosis, genetic testing, biotechnological research, environmental monitoring, and forensic science. However, the application of nucleic acid detection in various fields is hindered by the lack of sensitive, accurate, and inexpensive methods. This study introduces a simple approach to enhance the sensitivity for the accurate detection of nucleic acids. Our approach combined a split-probe strategy with in vitro translational amplification of reporter protein for signal generation to detect nucleic acids with high sensitivity and selectivity. This approach enables target-mediated translational amplification of reporter proteins by linking split probes in the presence of a target microRNA (miRNA). In particular, the fluorescence split-probe sensor adopts a reporter protein with various fluorescence wavelength regions, enabling the simultaneous detection of multiple target miRNAs. Moreover, luminescence detection by merely altering the reporter protein sequence can substantially enhance the sensitivity of detection of target miRNAs. Using this system, we analyzed and quantified target miRNAs in the total RNA extracted from cell lines and cell-derived extracellular vesicles with high specificity and accuracy. This split-probe sensor has potential as a powerful tool for the simple, sensitive, and specific detection of various target nucleic acids.

With the increasing age of our population, which is linked to a higher incidence of musculoskeletal diseases, there is a massive clinical need for bone implants. Porous scaffolds, usually offering a lower stiffness and allowing for the ingrowth of blood vessels and nerves, serve as an attractive alternative to conventional implants. Natural porous skeletons from marine sponges represent an array of evolutionarily optimized patterns, inspiring the design of biomaterials. In this study, cloud sponge-inspired scaffolds were designed and printed from a photocurable polymer, Clear Resin. These scaffolds were biofunctionalized by mussel-derived peptide MP-RGD, a recently developed peptide that contains a cyclic, bioactive RGD cell adhesion motif and catechol moieties, which provide the anchoring of the peptide to the surface. In in vitro cell culture assays with bone cells, significantly higher biocompatibility of three scaffolds, i.e., square, octagon, and hexagon cubes, in comparison to hollow and sphere inside cubes was shown. The performance of the cells regarding signaling was further enhanced by applying an MP-RGD coating. Consequently, these data demonstrate that both the structure of the scaffold and the coating contribute to the biocompatibility of the material. Three out of five MP-RGD-coated sponge-inspired scaffolds displayed superior biochemical properties and might guide material design for improved bone implants.

In recent years, antimicrobial hydrogels have attracted much attention in biomedical applications due to their biocompatibility and high water content. Glycyrrhizin (GA) is an antimicrobial that can form pH-dependent hydrogels due to the three carboxyl groups of GA that differ in pK_a value. The influence of GA protonation on the antimicrobial activity, however, has never been studied before. Therefore, we investigated the effect of the pH on the antimicrobial activity of GA against Pseudomonas aeruginosa, Staphylococcus aureus, MRSA, Staphylococcus epidermidis, Acinetobacter baumannii, Klebsiella pneumoniae, Klebsiella aerogenes, and two strains of Escherichia coli. In general, the antimicrobial activity of GA increases as a function of decreasing pH (and thus increasing protonation of GA). More specifically, fully protonated GA hydrogels (pH = 3) are required for growth inhibition and killing of E. coli UTI89 and Klebsiella in the suspension above the hydrogel, while the staphylococci strains and A. baumannii are already inhibited by fully deprotonated GA (pH = 6.8). P. aeruginosa and E. coli DH5α showed moderate susceptibility, as they are completely inhibited by a hydrogel at pH 3.8, containing partly protonated GA, but not by fully deprotonated GA (pH = 6.8). The antimicrobial activity of the hydrogel cannot solely be attributed to the resulting pH decrease of the suspension, as the presence of GA significantly increases the activity. Instead, this increased activity is due to the release of GA from the hydrogel into the suspension, where it directly interacts with the bacteria. Moreover, we provide evidence indicating that the pH dependency of the antimicrobial activity is due to differences in GA protonation state by treating the pathogens with GA solutions differing in their GA protonation distribution. Finally, we show by LC-MS that there is no chemical or enzymatic breakdown of GA. Overall, our results demonstrate that the pH influences not only the physical but also the antimicrobial properties of the GA hydrogels.

Expanded poly(tetrafluoroethylene) (ePTFE), obtained by the paste extrusion-stretching method, is a commonly used stent membrane material for the treatment of arterial stenosis or aneurysm in clinical practice. However, the structure of ePTFE is nonfibrous, which is not friendly to cells, and the equipment consumes a lot of energy and often requires the use of flammable and toxic lubricants. In this study, electrospinning was used to prepare PTFE vascular stent membranes, following plasma treatment, dopamine, and heparin grafting to obtain an anticoagulant surface. The morphology, structure, axial and circumferential tensile strength, porosity, water penetration pressure, and heparin-releasing behaviors of the samples were studied at first. Then, the experiments of blood compatibility, cytotoxicity, and in vivo subcutaneous implantation were conducted. Results showed that the PTFE electrospun tubular membrane has submicrometer to nanoscale fiber structures similar to the extracellular matrix. The axial and circumferential tensile strengths can reach 8.12 and 6.10 MPa, respectively, and the axial and circumferential elongations at break can reach 328.75% and 285.28%, respectively. It maintains higher porosity and water penetration pressure as well as a longer heparin-releasing period. It has a suitable hemolysis rate and superior anticoagulant properties. Dopamine and heparin modifications can facilitate the adhesion and proliferation of endothelial cells. Histological analysis of the PTFE electrospun tubular membrane showed no difference from the commercially available ePTFE graft.

Cancer is becoming a global threat, as the cancerous cells manipulate themselves frequently, resulting in mutants and more abnormalities. Early-stage and real-time detection of cancer biomarkers can provide insight into designing cost-effective diagnostic and therapeutic modalities. Nanoparticle and quantum dot (QD)-based approaches have been recognized as clinically relevant methods to detect disease biomarkers at the molecular level. Over decades, as an emergent noninvasive approach, photothermal therapy has evolved to eradicate cancer. Moreover, various structures, viz., nanoparticles, clusters, quantum dots, etc., have been tested as bioimaging and photothermal agents to identify tumor cells selectively. Among them, QDs have been recognized as versatile probes. They have attracted enormous attention for imaging and therapeutic applications due to their unique colloidal stability, optical and physicochemical properties, biocompatibility, easy surface conjugation, scalable production, etc. However, a few critical concerns of QDs, viz., precise engineering for molecular imaging and sensing, selective interaction with the biological system, and their associated toxicity, restrict their potential intervention in curing cancer and are yet to be explored. According to the U.S. Food and Drug Administration (FDA), there is no specific regulation for the approval of nanomedicines. Therefore, these nanomedicines undergo the traditional drug, biological, and device approval process. However, the market survey of QDs is increasing, and their prospects in translational nanomedicine are very promising. From this perspective, we discuss the importance of QDs for imaging, sensing, and therapeutic usage pertinent to cancer, especially in its early stages. Moreover, we also discuss the rapidly growing translational view of QDs. The long-term safety studies and cellular interaction of these QDs could enhance their visibility and bring photothermally active QDs to the clinical stage and concurrently to FDA approval.