Search Results (32)

Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription medication for pain reaching approximately USD 17.8 billion. Theranostic pain nanomedicine therefore emerges as an attractive analgesic strategy with the potential for increased efficacy, reduced side-effects, and treatment personalization. Theranostic nanomedicine combines drug delivery and diagnostic features, allowing for real-time monitoring of analgesic efficacy in vivo using molecular imaging. However, clinical translation of these nanomedicines are challenging due to complex manufacturing methodologies, lack of standardized quality control, and potentially high costs. Quality by Design (QbD) can navigate these challenges and lead to the development of an optimal pain nanomedicine. Our lab previously reported a macrophage-targeted perfluorocarbon nanoemulsion (PFC NE) that demonstrated analgesic efficacy across multiple rodent pain models in both sexes. Here, we report PFC-free, biphasic nanoemulsions formulated with a biocompatible and non-immunogenic plant-based coconut oil loaded with a COX-2 inhibitor and a clinical-grade, indocyanine green (ICG) near-infrared fluorescent (NIRF) dye for parenteral theranostic analgesic nanomedicine. Methods: Critical process parameters and material attributes were identified through the FMECA (Failure, Modes, Effects, and Criticality Analysis) method and optimized using a 3 × 2 full-factorial design of experiments. We investigated the impact of the oil-to-surfactant ratio (w/w) with three different surfactant systems on the colloidal properties of NE. Small-scale (100 mL) batches were manufactured using sonication and microfluidization, and the final formulation was scaled up to 500 mL with microfluidization. The colloidal stability of NE was assessed using dynamic light scattering (DLS) and drug quantification was conducted through reverse-phase HPLC. An in vitro drug release study was conducted using the dialysis bag method, accompanied by HPLC quantification. The formulation was further evaluated for cell viability, cellular uptake, and COX-2 inhibition in the RAW 264.7 macrophage cell line. Results: Nanoemulsion droplet size increased with a higher oil-to-surfactant ratio (w/w) but was no significant impact by the type of surfactant system used. Thermal cycling and serum stability studies confirmed NE colloidal stability upon exposure to high and low temperatures and biological fluids. We also demonstrated the necessity of a solubilizer for long-term fluorescence stability of ICG. The nanoemulsion showed no cellular toxicity and effectively inhibited PGE2 in activated macrophages. Conclusions: To our knowledge, this is the first instance of a celecoxib-loaded theranostic platform developed using a plant-derived hydrocarbon oil, applying the QbD approach that demonstrated COX-2 inhibition. Full article

Hydrogels have emerged as multifunctional biomaterials in cardiac surgery, offering promising solutions for myocardial regeneration, adhesion prevention, valve engineering, and localized drug and gene delivery. Their high water content, biocompatibility, and mechanical tunability enable close emulation of the cardiac extracellular matrix, supporting cellular viability and integration under dynamic physiological conditions. In myocardial repair, injectable and patch-forming hydrogels have been shown to be effective in reducing infarct size, promoting angiogenesis, and preserving contractile function. Hydrogel coatings and films have been designed as adhesion barriers to minimize pericardial adhesions after cardiotomy and improve reoperative safety. In heart valve and patch engineering, hydrogels contribute to scaffold design by providing bio-instructive, mechanically resilient, and printable matrices that are compatible with 3D fabrication. Furthermore, hydrogels serve as localized delivery platforms for small molecules, proteins, and nucleic acids, enabling sustained or stimuli-responsive release while minimizing systemic toxicity. Despite these advances, challenges such as mechanical durability, immune compatibility, and translational scalability persist. Ongoing innovations in smart polymer chemistry, hybrid composite design, and patient-specific manufacturing are addressing these limitations. This review aims to provide an integrated perspective on the application of hydrogels in cardiac surgery. The relevant literature was identified through a narrative search of PubMed, Scopus, Web of Science, Embase, and Google Scholar. Taken together, hydrogels offer a uniquely versatile and clinically translatable platform for addressing the multifaceted challenges of cardiac surgery. Hydrogels are poised to redefine clinical strategies in cardiac surgery by enabling tailored, bioresponsive, and functionally integrated therapies. Full article

The development of vaccines against viral infections has advanced rapidly over the past century, propelled by innovations in laboratory and molecular technologies. These advances have expanded the range of vaccine platforms beyond live-attenuated and inactivated vaccines to include recombinant platforms, such as subunit proteins and virus-like particles (VLPs), and more recently, mRNA-based vaccines, while also enhancing methods for evaluating vaccine performance. Despite these innovations, a persistent challenge remains: the inherent complexity and heterogeneity of immune responses continue to impede efforts to achieve consistently effective and durable protection across diverse populations. Single-cell technologies have emerged as transformative tools for dissecting this immune heterogeneity, providing comprehensive and granular insights into cellular phenotypes, functional states, and dynamic host–pathogen interactions. In this review, we examine how single-cell epigenomic, transcriptomic, proteomic, and multi-omics approaches are being integrated across all stages of vaccine development—from infection-informed discovery to guide vaccine design, to high-resolution evaluation of efficacy, and refinement of cell lines for manufacturing. Through representative studies, we highlight how insights from these technologies contribute to the rational design of more effective vaccines and support the development of personalized vaccination strategies. Full article

To address anisotropy challenges in electric arc-based additive manufacturing of Inconel 718 alloy, this study develops a novel wire feeding oscillated double-pulsed gas tungsten arc welding additive manufacturing method (DP-GTA-AM) enabling precise thermal-mass transfer control. Series of crack-free thin-walled Inconel 718 alloy parts were successfully obtained by this proposed approach, and the microstructure and mechanical properties of the parts were thoroughly studied. The results indicate that the microstructure changes from dendrites and cellular crystals in the bottom to equiaxed grains in the midsection and entirely equiaxed crystals in the top, resulting in notable grain refinement. With an average grain size of 61.76 μm and an average length of 83.31 μm of large angle grain boundaries, the density of the <001> direction reaches 19.45. The difference in tensile strength and ductility between the horizontal and the vertical directions decreases to 6.3 MPa and 0.38%, which significantly diminishes anisotropy. Fractographic analysis confirms quasi-cleavage failure with homogeneous dimple distribution, demonstrating effective anisotropy mitigation through controlled solidification dynamics. Full article

Magnetic polymeric conduits are developing as revolutionary materials in regenerative medicine, providing exceptional benefits in directing tissue healing, improving targeted medication administration, and facilitating remote control via external magnetic fields. The present article offers a thorough examination of current progress in the design, construction, and functionalization of these hybrid systems. The integration of magnetic nanoparticles into polymeric matrices confers distinctive features, including regulated alignment, improved cellular motility, and targeted medicinal delivery, while preserving structural integrity. Moreover, the incorporation of multifunctional attributes, such as electrical conductivity for cerebral stimulation and optical characteristics for real-time imaging, expands their range of applications. Essential studies indicate that the dimensions, morphology, surface chemistry, and composition of magnetic nanoparticles significantly affect their biocompatibility, degrading characteristics, and overall efficacy. Notwithstanding considerable advancements, issues concerning long-term biocompatibility, biodegradability, and scalability persist, in addition to the must for uniform regulatory frameworks to facilitate clinical translation. Progress in additive manufacturing and nanotechnology is overcoming these obstacles, facilitating the creation of dynamic and adaptive conduit structures designed for particular biomedical requirements. Magnetic polymeric conduits, by integrating usefulness and safety, are set to transform regenerative therapies, presenting a new avenue for customized medicine and advanced healthcare solutions. Full article

The combination of molybdenum disulfide (MoS₂) with plasmonic nanomaterials has opened up new possibilities in biological applications by combining MoS₂’s biocompatibility and high surface area with the optical sensitivity of plasmonic metals. These MoS₂–plasmonic hybrid systems hold great promise in areas such as biosensing, bioimaging, and phototherapy, where their complementary properties facilitate improved detection, real-time visualization, and targeted therapeutic interventions. MoS₂’s adjustable optical features, combined with the plasmon resonance of noble metals such as gold and silver, enhance signal amplification, enabling detailed imaging and selective photothermal or photodynamic therapies while minimizing effects on healthy tissue. This review explores various synthesis strategies for MoS₂–plasmonic hybrids, including seed-mediated growth, in situ deposition, and heterojunction formation, which enable tailored configurations optimized for specific biological applications. The primary focus areas include highly sensitive biosensors for detecting cancer and infectious disease biomarkers, high-resolution imaging of cellular dynamics, and the development of phototherapy methods that allow for accurate tumor ablation through light-induced thermal and reactive oxygen species generation. Despite the promising advancements of MoS₂–plasmonic hybrids, translating these platforms into clinical practice requires overcoming considerable challenges, such as synthesis reproducibility, toxicity, stability in physiological conditions, targeted delivery, and scalable manufacturing. Addressing these challenges is essential for realizing their potential as next-generation tools in diagnostics and targeted therapies. Full article

Hydrogen, with its high energy density and zero greenhouse gas emissions, is an exceptional energy vector, pivotal for a sustainable energy future. Ammonia, serving as a practical and cost-effective hydrogen carrier, offers a secure method for hydrogen storage and transport. The decomposition of ammonia into hydrogen is a crucial process for producing green hydrogen, enabling its use in applications ranging from clean energy generation to fueling hydrogen-powered vehicles, thereby advancing the transition to a carbon-free energy economy. This study investigates the catalytic performance of various 3D-printed porous supports based on periodic open cellular structures (POCS) and triply periodic minimal surface (TPMS) architecture manufactured from IN625 nickel alloy powder using the laser powder bed fusion (LPBF) technique. The POCS and TPMS, featuring geometries including BCC, Kelvin, and Gyroid, were analyzed for cell size, strut/sheet diameter, porosity, and specific surface area. Pressure drop analyses demonstrated correlations between structural parameters and fluid dynamics, with BCC structures exhibiting lower pressure drops due to their higher porosity and the open channel network. The dip/spin coating method was successfully applied to activate the supports with a commercial Ru/Al₂O₃ catalyst, achieving uniform coverage crucial for catalytic performance. Among the tested geometries, the Gyroid structure showed superior catalytic activity towards ammonia decomposition, attributed to its efficient mass transfer pathways. This study highlights the importance of structural design in optimizing catalytic processes and suggests the Gyroid structure as a promising candidate for improving reactor efficiency and compactness in hydrogen production systems. Full article

Multiple myeloma (MM) treatment remains challenging due to its relapsed/refractory disease course as well as intra- and inter-patient heterogeneity. Cellular immunotherapies, especially chimeric antigen receptor (CAR)-T cells targeting B cell maturation antigen (BCMA), mark a major breakthrough, achieving long-lasting remissions and instilling hope for a potential cure. While ongoing clinical trials are increasingly driving approved cellular products towards earlier lines of therapy, novel targets as well as advanced approaches employing natural killer (NK) cells or dendritic cell (DC) vaccines are currently under investigation. Treatment resistance, driven by tumor-intrinsic factors such as antigen escape and the intricate dynamics of the tumor microenvironment (TME), along with emerging side effects such as movement and neurocognitive treatment-emergent adverse events (MNTs), are the major limitations of approved cellular therapies. To improve efficacy and overcome resistance, cutting-edge research is exploring strategies to target the microenvironment as well as synergistic combinatorial approaches. Recent advances in CAR-T cell production involve shortened manufacturing protocols and “off-the-shelf” CAR-T cells, aiming at decreasing socioeconomic barriers and thereby increasing patient access to this potential lifesaving therapy. In this review, we provide an extensive overview of the evolving field of cellular therapies for MM, underlining the potential to achieve long-lasting responses. Full article

With the recent surge in the development of highly selective probes, fluorescence microscopy has become one of the most widely used approaches to studying cellular properties and signaling in living cells and tissues. Traditionally, microscopy image analysis heavily relies on manufacturer-supplied software, which often demands extensive training and lacks automation capabilities for handling diverse datasets. A critical challenge arises if the fluorophores employed exhibit low brightness and a low signal-to-noise ratio (SNR). Consequently, manual intervention may become a necessity, introducing variability in the analysis outcomes even for identical samples when analyzed by different users. This leads to the incorporation of blinded analysis, which ensures that the outcome is free from user bias to a certain extent but is extremely time-consuming. To overcome these issues, we developed a tool called DL-SCAN that automatically segments and analyzes fluorophore-stained regions of interest such as cell bodies in fluorescence microscopy images using deep learning. We demonstrate the program’s ability to automate cell identification and study cellular ion dynamics using synthetic image stacks with varying SNR. This is followed by its application to experimental Na⁺ and Ca²⁺ imaging data from neurons and astrocytes in mouse brain tissue slices exposed to transient chemical ischemia. The results from DL-SCAN are consistent, reproducible, and free from user bias, allowing efficient and rapid analysis of experimental data in an objective manner. The open-source nature of the tool also provides room for modification and extension to analyze other forms of microscopy images specific to the dynamics of different ions in other cell types. Full article

Laminar flow offers significant potential for increasing the energy efficiency of future transport aircraft. At the Cluster of Excellence SE²A—Sustainable and Energy-Efficient Aviation—the laminarization of the wing by means of hybrid laminar flow control (HLFC) is being investigated. The aim is to maintain the boundary layer as laminar for up to 80% of the chord length of the wing. This is achieved by active suction on the leading edge and the rear part of the wing. The suction panels are constructed with a thin micro-perforated skin and a supporting open-cellular core structure. The mechanical requirements for this kind of sandwich structure vary depending on its position of usage. The suction panel on the leading edge must be able to sustain bird strikes, while the suction panel on the rear part must sustain bending loads from the deformation of the wing. The objective of this study was to investigate the energy absorption properties of a triply periodic minimal surface (TPMS) structure that can be used as a bird strike-resistant core in the wing leading edge. To this end, cubic-sheet-based gyroid specimens of different polymeric materials and different geometric dimensions were manufactured using additive manufacturing processes. The specimens were then tested under quasi-static compression and dynamic crushing loading until failure. It was found that the mechanical behavior was dependent on the material, the unit cell size, the relative density, and the loading rate. In general, the weight-specific energy absorption (SEA) at 50% compaction increased with increasing relative density. Polyurethane specimens exhibited an increase in SEA with increasing loading rate, as opposed to the specimens of the other investigated polymers. A smaller unit cell size induced a more consistent energy absorption, due to the higher plateau force. Full article

Traditional prosthetic liners are often limited in customization due to constraints in manufacturing processes and materials. Typically made from non-compressible elastomers, these liners can cause discomfort through uneven contact pressures and inadequate adaptation to the complex shape of the residual limb. This study explores the development of bioinspired cellular metamaterial prosthetic liners, designed using additive manufacturing techniques to improve comfort by reducing contact pressure and redistributing deformation at the limb–prosthesis interface. The gyroid unit cell was selected due to its favorable isotropic properties, ease of manufacturing, and ability to distribute loads efficiently. Following the initial unit cell identification analysis, the results from the uniaxial compression test on the metamaterial cellular samples were used to develop a multilinear material model, approximating the response of the metamaterial structure. Finite Element Analysis (FEA) using a previously developed generic limb–liner–socket model was employed to simulate and compare the biomechanical behavior of these novel liners against conventional silicone liners, focusing on key parameters such as peak contact pressure and liner deformation during donning, heel strike, and the push-off phase of the gait cycle. The results showed that while silicone liners provide good overall contact pressure reduction, cellular liners offer superior customization and performance optimization. The soft cellular liner significantly reduced peak contact pressure during donning compared to silicone liners but exhibited higher deformation, making it more suitable for sedentary individuals. In contrast, medium and hard cellular liners outperformed silicone liners for active individuals by reducing both contact pressure and deformation during dynamic gait phases, thereby enhancing stability. Specifically, a medium-density liner (10% infill) balanced contact pressure reduction with low deformation, offering a balance of comfort and stability. The hard cellular liner, ideal for high-impact activities, provided superior shape retention and support with lower liner deformation and comparable contact pressures to silicone liners. The results show that customizable stiffness in cellular metamaterial liners enables personalized design to address individual needs, whether focusing on comfort, stability, or both. These findings suggest that 3D-printed metamaterial liners could be a promising alternative to traditional prosthetic materials, warranting further research and clinical validation. Full article

Wound healing is a dynamic process involving a complex interaction between many cells and mediators. Magnesium (Mg) is an essential element for cell stabilization. Mg was reported to stimulate the proliferation and migration of endothelial cells in angiogenesis in vitro. However, the function of Mg in wound healing is not known. We observed that the expression level of Mg in human wound tissue fluid was only 10% of that found in human blood serum. To confirm whether Mg is a suitable wound dressing material, we fabricated a Mg- or Mg-silver (Ag)-based polyethylene dressing to study its effect on wound healing. We observed that Mg and Ag were stably preserved in the constructed material and were able to be rapidly released in the moist environment. We also observed that the Mg-based dressing had good cellular compatibility without harmful extractables. Furthermore, Mg enhanced the antibacterial activity of Ag. In line with the observed increase in fibroblast migration in vitro, the Mg-Ag-based dressing improved acute and chronic wound repairs via an increase in neovascularization and basal cell proliferation. The present results show that a Mg-Ag-based coating can be manufactured as an optimal dressing for adjuvant wound therapy. Full article

Periodic truss-based lattice materials, a particular subset of cellular solids that generally have superior specific properties as compared to monolithic materials, offer regularity and predictability that irregular foams do not. Significant advancements in alternative technologies—such as additive manufacturing—have allowed for the fabrication of these uniquely complex materials, thus boosting their research and development within industries and scientific communities. However, there have been limitations in the comparison of results for these materials between different studies reported in the literature due to differences in analysis approaches, parent materials, and boundary and initial conditions considered. Further hindering the comparison ability was that the literature generally only focused on one or a select few topologies. With a particular focus on the crashworthiness of lattice topologies, this paper presents a comprehensive study of the impact performance of 24 topologies under dynamic impact loading. Using steel alloy parent material (manufactured using Selective Laser Melting), a numerical study of the impact performance was conducted with 16 different impact energy–speed pairs. It was possible to observe the overarching trends in crashworthiness parameters, including plateau stress, densification strain, impact efficiency, and absorbed energy for a wide range of 3D lattice topologies at three relative densities. While there was no observed distinct division between the results of bending and stretching topologies, the presence of struts aligned in the impact direction did have a significant effect on the energy absorption efficiency of the lattice; topologies with struts aligned in that direction had lower efficiencies as compared to topologies without. Full article

Even though tissue-engineered medicines are under intense academic, clinical, and commercial investigation, only a handful of products have been commercialised, primarily due to the costs associated with their prolonged manufacturing. While macromolecular crowding has been shown to enhance and accelerate extracellular matrix deposition in eukaryotic cell culture, possibly offering a solution in this procrastinating tissue-engineered medicine development, there is still no widely accepted macromolecular crowding agent. With these in mind, we herein assessed the potential of gum Arabic, gum gellan, gum karaya, and gum xanthan as macromolecular crowding agents in WS1 skin fibroblast cultures (no macromolecular crowding and carrageenan were used as a control). Dynamic light scattering analysis revealed that all macromolecules had negative charge and were polydispersed. None of the macromolecules affected basic cellular function. At day 7 (the longest time point assessed), gel electrophoresis analysis revealed that all macromolecules significantly increased collagen type I deposition in comparison to the non-macromolecular crowding group. Also at day 7, immunofluorescence analysis revealed that carrageenan; the 50 µg/mL, 75 µg/mL, and 100 µg/mL gum gellan; and the 500 µg/mL and 1000 µg/mL gum xanthan significantly increased both collagen type I and collagen type III deposition and only carrageenan significantly increased collagen type V deposition, all in comparison to the non-macromolecular crowding group at the respective time point. This preliminary study demonstrates the potential of gums as macromolecular crowding agents, but more detailed biological studies are needed to fully exploit their potential in the development of tissue-engineered medicines. Full article

Surface wrinkling provides an approach to fabricate micron and sub-micron-level biomaterial topographies that can mimic features of the dynamic, in vivo cell environment and guide cell adhesion, alignment, and differentiation. Most wrinkling research to date has used planar, two-dimensional (2D) substrates, and wrinkling work on three-dimensional (3D) structures has been limited. To enable wrinkle formation on architecturally complex, biomimetic 3D structures, here, we report a simple, low-cost experimental wrinkling approach that combines natural silk fibroin films with a recently developed advanced manufacturing technique for programming strain in complex 3D shape–memory polymer (SMP) scaffolds. By systematically investigating the influence of SMP programmed strain magnitude, silk film thickness, and aqueous media on wrinkle morphology and stability, we reveal how to generate and tune silk wrinkles on the micron and sub-micron scale. We find that increasing SMP programmed strain magnitude increases wavelength and decreases amplitudes of silk wrinkled topographies, while increasing silk film thickness increases wavelength and amplitude. Silk wrinkles persist after 24 h in cell culture medium. Wrinkled topographies demonstrate high cell viability and attachment. These findings suggest the potential for fabricating biomimetic cellular microenvironments that can advance understanding and control of cell–material interactions in engineering tissue constructs. Full article