Advanced Nanobiomed Research最新文献

Eggshell-Based Biomaterials

Eggshell-based biomaterials provide a sustainable and versatile platform for medical applications, including hard and soft tissue regeneration, drug delivery technologies, and biosensing applications. With their biomimetic mineralization ability, excellent biocompatibility, and a unique combination of bioactive components and structural properties, eggshells hold transformative potential to address critical unmet needs in the healthcare industry. More details can be found in article 2400120 by Gulden Camci-Unal and co-workers.

Implantable neural electrode arrays can be inserted in the brain to provide single-cell electrophysiology recording for neuroscience research and brain–machine interface applications. However, maintaining signal quality over time is complicated by inflammatory tissue responses and degradation of electrode materials. Organic electrode coatings offer a solution by enhancing recording and stimulation capabilities, including reduced impedance, increased charge injection capacity, and the ability to incorporate and release anti-inflammatory drugs. Herein, acid-functionalized multiwalled carbon nanotubes (CNTs) loaded with dexamethasone (Dex) are incorporated into poly(3,4-ethylendioxythiophene) (PEDOT) as electrode coatings. The electrochemical stability and recording performance of the PEDOT/CNT/Dex coating over an extended period of ≈18 months are investigated. Cyclic voltammetry (CV) stimulation is used to release Dex in half of the recording sites during the first 11 days of implantation to reduce the acute inflammation. The PEDOT/CNT/Dex-coated floating microelectrode arrays demonstrate stable in vivo electrode impedance and successful detection of visually evoked neural activity from the rat visual cortex even at chronic time points. Additionally, the CV-stimulated sites exhibit higher single-unit (SU) recording yield, amplitudes, and signal-to-noise ratio compared to unstimulated sites. These results highlight the potential of anti-inflammatory treatments to improve the quality and longevity of chronic neural recordings.

Cancer remains a leading cause of mortality and morbidity worldwide. Consequently, the scientific community continues to pursue improvements in diagnostic methods and subsequent treatments. To enhance treatment efficacy and reduce the probability of adverse outcomes, reliable and sensitive diagnostic methods are essential. A potential solution may lie in the synergy between nanotechnology and optical biosensors, as they can provide exceptional sensitivity in the detection of disease biomarkers. This review focuses on fluorescent DNA probes assembled onto metal nanoparticles for cancer-related applications. These hybrid biosensors exhibit remarkable and versatile optical properties enabling to enhance signal emission by orders of magnitude. In these configurations, metallic particles function as optical antennas for fluorescent dyes, significantly increasing their photon emission rates. This review presents a novel perspective on recent advancements in cancer diagnostics and treatment utilizing hybrid biosensors. Current methodologies for cancer diagnostics are examined, toward elucidating their advantages and limitations. The subject matter is critically evaluated, and fundamental concepts are explored to assess the most promising avenues for clinical applications. These biosensors may potentially integrate into medical practice and healthcare in the near future, both for the diagnosis and prognosis of cancer, as well as for precision (P4) medicine.

Hydrodynamic Cavitation Based Clot-on-a-Chip Platform

This artwork highlights the functionality of the developed new-generation microfluidic platform, which is called the “clot-on-a-chip (CoC)” platform and is based on hydrodynamic cavitation at the microscale. Complete blood clot erosion and removal can be realized with this CoC platform. More details can be found in the article 2400112 by Morteza Ghorbani, Ali Koşar, and co-workers.

Breast cancer is a substantial source of morbidity and mortality worldwide. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are the primary biomarkers which inform breast cancer treatment. Although endocrine therapy for ER+ patients is widely available, there is a need for increased access to low-cost, rapid, and accurate ER testing methods. In this work, we designed a near-infrared optical nanosensor using single-walled carbon nanotubes (SWCNT) as the transducer and an anti-ERα antibody as the recognition element. We evaluated the nanosensor in vitro prior to testing with 26 breast cancer samples which were collected by scraping the cut surface of fresh, surgically resected tumors. Twenty samples were ER+, and six ER−, representing 13 unique patients. We found that the nanosensor can differentiate ER− from ER+ patient biopsies through a shift in its center wavelength upon sample addition. Receiver operating characteristic area under the curve analyses determined that the strongest classifier with an AUC of 0.94 was the (7,5) SWCNT after direct incubation and measurement, and without further processing. We anticipate that further testing and development of this nanosensor may push its utility toward field-deployable, rapid ER subtyping with the potential for additional molecular marker profiling.

Digital Microfluidics

In article 2400044, Nam-Trung Nguyen and co-workers introduce liquid beads, liquid sample encapsulated in a solid shell, for sample partitioning of digital loop-mediated isothermal amplification (dLAMP). Accurate and reproducible the quantitative detection of a gene cluster of leaf scald disease was conducted using this dLAMP approach. The results demonstrate the robust performance of this technique as compared to droplet-based and conventional quantitative approaches.

Baghdadite (BAG, Ca₃ZrSi₂O₉), a calcium silicate compound with zirconium incorporation, shows significant potential in medical implants. However, its susceptibility to infections poses a considerable challenge. To tackle this problem, doping biocompatible magnesium (Mg) into BAG to create Mg-BAG enhances antibacterial activity and prevents infection in orthopedic implants. Mg-BAG demonstrates effectiveness against Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa. This study finds that the antibacterial activity of Mg-BAG is multifaced including causing the generation of reactive oxygen species (ROS) within cells and disrupting membrane potential, resulting in leakage of intracellular contents. The synchrotron macro attenuated total reflectance Fourier-transform infrared microspectroscopy shows the impact of Mg-BAG on bacteria, resulting in modifications to biomolecules such as lipids, protein structures, and the stability of nucleic acids. The combined effect of Mg ions (Mg²⁺) and intracellular ROS formation contributes to the disruption of biomolecules and bacterial cell death. Mg-BAG is a promising next-generation bioceramic offering innovative nonantibiotic solutions for preventing infection.

The receptor-binding domain (RBD) of the SARS-CoV-2 virus spike protein has emerged as a promising target for the generation of neutralizing antibodies. Although the RBD subunit is more stable than its encoding mRNA, RBD is poorly immunogenic. It is hypothesized that this limitation can be overcome by sustained coadministration with a more potent and optimized adjuvant than standard adjuvants. One such candidate adjuvant, cGAMP, exhibits promising potency via activation of the antiviral STING pathway. Unfortunately, delivery of cGAMP as a therapeutic exhibits poor performance due to poor pharmacokinetics and pharmacodynamics from rapid excretion and degradation. To overcome these limitations, it is sought to create an artificial immunological niche enabling the slow release of cGAMP and RBD to mimic natural infections in which immune-activating molecules are colocalized with antigen. Specifically, through coencapsulation of cGAMP and RBD in an injectable polymer-nanoparticle (PNP) hydrogel, the cGAMP-adjuvanted hydrogel vaccine elicits more potent, durable, and broad antibody responses with improved neutralization as compared to dose-matched bolus controls and hydrogel-based vaccines lacking cGAMP. The cGAMP-adjuvanted hydrogel platform can be further explored for the delivery of other antigens to enhance immunity against a broad range of pathogens.

Upon injury, regenerating skin is metabolically active and requires oxygen for physiological processes related to wound healing. Such processes can be halted in hypoxic conditions common in chronic wounds. Microneedle arrays (MNAs) have been demonstrated to improve therapeutic delivery and wound healing. Recently, few studies have explored the use of oxygen-releasing MNAs; however, they involve complex manufacturing and handling and fail to eliminate cytotoxic byproducts. To address these challenges, biodegradable and mechanically robust gelatin methacryloyl-based MNAs are developed that can penetrate the tissue and release oxygen upon exposure to interstitial fluid and wound exudates. The oxygen release rate and biocompatibility of the developed MNAs with different compositions are evaluated and optimized. Interestingly, in vitro studies demonstrate that the optimized compositions can release oxygen at therapeutic levels and significantly increase viability of chronically hypoxic cells to match that of normoxic cells. In vivo studies further confirm that the optimized oxygen-generating MNAs do not cause any harm or impair healing in a murine model of acute skin injury. Additionally, transcriptomic analysis reveals upregulation of key pathways related to fibroblast motility, lipid metabolism, and a marked reduction in inflammatory signaling, all of which contribute to improved wound healing. The developed strategy can introduce new opportunities in elimination of hypoxia and therefore treatment of chronic wounds.

Bronchospheres have emerged as a promising in vitro model toward probing questions on organ development and disease. Several organoid models, including from airway (e.g., bronchial, tracheal) cells, require three-dimensional (3D) Matrigel, a complex mouse tumor-derived matrix that typically leads to heterogeneous size and structures. Synthetic and naturally derived polymeric hydrogels show increased opportunities as an alternative to Matrigel culture. In addition, recent advances in hydrogel-based microcavities (i.e., microwells) have shown improved control over organoid size, structure, and composition. Here, we build upon this approach and describe the fabrication and characterization of microwell hydrogels based on other polymers, including diacrylated poly(ethylene glycol), agarose, methacrylated gelatin, and norbornene-modified hyaluronic acid. Using these microwell hydrogels, human bronchial epithelial cells and lung fibroblasts readily assemble into viable cyst-like bronchospheres. The study shows that the cellular composition regulates the formation and structure of the bronchosphere which also depends on the type and adhesiveness of the hydrogel. Furthermore, both hydrogel type and cellular composition influence the amount and composition of deposited extracellular matrix within the microwells. This hydrogel fabrication platform provides an accessible in vitro culture platform for the formation and growth of bronchospheres which can be extended to the culture of other organoid systems.