Advanced Biomedical Applications Research Articles

Exploring the Advanced Synthesis Strategies and Biomedical Applications of Iron Oxide-Based Nanozymes: A Comprehensive Review

Exploring the Advanced Synthesis Strategies and Biomedical Applications of Iron Oxide-Based Nanozymes: A Comprehensive Review

Intracellularly manipulable aggregation of the aggregation-induced emission luminogens

Biophotonics has seen significant advancements with the development of optical imaging techniques facilitating the noninvasive detection of biologically relevant species. Aggregation-induced emission (AIE) materials have emerged as a novel class of luminogens exhibiting enhanced luminescence or photodynamic efficiency in the aggregated state, making them ideal for biomedical applications. The intracellularly controlled aggregation of aggregate-induced emission luminogens (AIEgens) enables high-resolution imaging of intracellular targets and diagnosis of related diseases, and enables disease therapy by exploiting the novel properties of aggregates. This review provides an in-depth analysis of the strategies employed to modulate the aggregation of AIEgens, focusing on the importance of molecular modifications to improve hydrophilicity and achieve precise control over the intercellular aggregation of AIEgens. Furthermore, the representative applications of AIEgens in bioimaging, such as enzyme activity monitoring, protein tracking, organelle function monitoring, and in vivo tumor-specific therapeutics, are reviewed. Additionally, we outline the challenges and future opportunities for AIE research, emphasizing the importance of the strategies for realizing the precisely controllable aggregation of AIEgens inside cells and the need for extending AIEgens’ absorption and emission wavelengths. This review aims to elucidate the rational development of responsive AIEgens for advanced biomedical applications.

Evaluation of titanium dioxide and tantalum pentoxide nanoparticles for coating NiTi archwires in orthodontics: An in vitro study

Background: This study aims to enhance the biocompatibility of Nickel–Titanium (NiTi) alloy by developing a new coating using titanium dioxide (TiO2) and titanium pentoxide (Ta2O5) through direct current (DC) reactive sputtering technology. Materials and methods: Two distinct coating materials, namely, TiO2 and Ta2O5, were used to fabricate NiTi orthodontic archwires with improved surface properties. TiO2 nanoparticles, with thickness ranging from 21.90 nm to 31.93 nm, were deposited onto NiTi alloy substrates through DC reactive sputtering deposition under different power conditions. Results: X-ray diffraction and field emission scanning electron microscopy validated the uniformity and morphology of the coatings. Immersion tests in simulated body fluid (SBF) revealed significant hydroxyapatite layer growth on TiO2-coated NiTi, especially at a sputtering power of 240 W. Reduced nickel ion release was observed on TiO2 nanoparticles with a thickness of 21.90 nm at 50 W sputtering power compared with 31.93 nm-thick nanoparticles at 240 W. Ta2O5 thin films were deposited on NiTi substrates through DC magnetron reactive sputtering at ~100 °C with a deposition power of 50 W. Structural and morphological analyses through optical microscopy and X-ray diffraction, atomic force microscopy, and scanning electron microscopy revealed the homogeneity and low roughness of the coatings. Biocompatibility assessments in artificial saliva and SBF solutions established that Ta2O5-coated NiTi alloys exhibited superior electrochemical behavior, enhanced corrosion resistance, and diminished Ni ion release compared with uncoated specimens. Conclusion: TiO2 and Ta2O5 coatings not only improved the biocompatibility of NiTi orthodontic archwires but also presented a promising path for advanced biomedical applications. These coatings have potential in improving the cellular behavior and performance of NiTi-based orthodontic devices.

Advances in Biomedical Applications of Hydrogels from Seaweed-Derived Sulfated Polysaccharides: Carrageenan, Fucoidan, and Ulvan

Advances in Biomedical Applications of Hydrogels from Seaweed-Derived Sulfated Polysaccharides: Carrageenan, Fucoidan, and Ulvan

Experimental investigation on the tribo-mechanical behavior of PMMA reinforced by solid lubricant filler for dental implant applications

This study investigates the enhancement of mechanical and tribological behavior in polymethyl methacrylate (PMMA) composites reinforced with graphene oxide (GO) as a solid lubricant filler for advanced biomedical applications, particularly dental implants. PMMA/GO composites were prepared with varying weight percentages of GO (0, 0.2, 0.5, 0.7, and 1 wt. %) to assess their impact on material performance. A noteworthy improvement in both tensile strength and Young’s modulus was detected, reaching up to 141% and 10.6%, respectively, at optimized GO loadings of 1%. Microstructural analysis utilizing scanning electron microscopy for the worn surface revealed enhanced dispersion and interfacial adhesion between GO and the PMMA matrix, reinforcing mechanical coherence. Tribological properties also demonstrated enhancement, with PMMA composites containing 1 wt. % GO exhibiting optimal mechanical and tribological characteristics compared to lower weight fractions. Moreover, microscopic examination revealed a shift in the wear mechanism of the PMMA-GO composite, which was attributed to the lower friction coefficient obtained by GO integration.

Influence of ageing time on crystallization kinetics and hydroxyapatite Mimicking Silicorhenanite (β-Na2Ca4(PO4)2SiO4) phase evolution in 45S5® bioactive glass for advanced biomedical applications

Among multiple phases obtained while synthesizing bioactive glass, the phosphate-rich Silicorhenanite phase is achieved only at high temperatures. The novel outcome of this work is that sol-gel routed 45S5 bioactive glass was synthesized successfully by permutating the period of ageing and achieved the Silicorhenanite phase at 700 °C without compromising biocompatibility. The process of ‘Ostwald ripening’ was observed among the biomaterials where A24 and A72 exhibited a similar trend and A48 and A96 behaved alike. Rietveld Refinement confirms the elevation of the Silicorhenanite (β-Na2Ca4(PO4)2SiO4) phase upon increasing the ageing time over the Combeite (Na2Ca2Si3O9) phase. Since A72 exhibits compressive strain and smaller crystallite size, it lacks erythrocyte compatibility, and protein adsorption, and has an exceptionally low surface area. This study emphasizes the stability and multiple physio-chemical properties of 45S5 Bioactive glass during the ageing period, which is an imperious parameter for producing biomedically beneficial glass products, especially porous scaffolds and implant coatings.

Viscous influences on impulsively generated focused jets

Impulsively generated focused jets play a significant role in various applications, including inkjet printing, needle-free drug delivery, and microfluidic devices. As the demand for generating jets and droplets from medium to highly viscous liquids increases, understanding the role of viscosity in jetting dynamics becomes crucial. While previous studies have examined the viscous effects on walls, the impact on free surfaces has not been thoroughly understood. This study aims to bridge this gap by integrating experiments with numerical simulations to investigate the viscous effects on focused jet formation. We demonstrate that mass and momentum transfer along the tangential direction of the free surface contribute to focused jet formation, and viscosity plays a key role in this transfer process. The viscosity-induced diffusion of the shear flow and vorticity near the free surface reduces the jet speed. Based on experimental observations and simulation results, we propose an equation to predict the viscous jet velocity. These findings offer new perspectives on viscous interface dynamics in advanced manufacturing and biomedical applications. Published by the American Physical Society 2024

Mechanics and thermodynamics of multivalent-binding induced shrinkage of hydrogels

Understanding the fundamental mechanism of shrink hydrogel sensors necessitates a complete comprehension of analyte-centered multivalent binding that occurs within their salt-rich microenvironments. However, the mechanics and thermodynamics governing this phenomenon remain insufficiently understood. Here, we aim to derive a theoretical framework that examines the impact of temporary cross-link formation on the hydrogel shrinkage due to specific binding interaction between the fixed receptors and the multivalent analytes. As a highlight of our theory, we mathematically quantify the hydrogels’ permanent and temporary cross-links using statistical thermodynamics to describe the multivalent complexation with different binding degrees while accounting for molecular-level transport factors when predicting the sensor’s shrinking characteristics. Consequently, our theory unveils the upper bounds set by the external analyte concentration and analyte binding valency onto the actuation sensitivity of these sensors, whereby tuning the receptor density permits further modulation of their performances. These findings tightly correlate the microscopic properties of the analyte and hydrogel to the macroscopic behaviors of shrink sensors, facilitating a structured design regime for advanced biomedical applications.

Superimposed Electric Field Enhanced Electrospray for High-Throughput and Consistent Cell Encapsulation.

Cell encapsulation technology, crucial for advanced biomedical applications, faces challenges in existing microfluidic and electrospray methods. Microfluidic techniques, while precise, can damage vulnerable cells, and conventional electrospray methods often encounter instability and capsule breakage during high-throughput encapsulation. Inspired by the transformation of the working state from unstable dripping to stable jetting triggered by local electric potential, this study introduces a superimposed electric field (SEF)-enhanced electrospray method for cell encapsulation, with improved stability and biocompatibility. Utilizing stiffness theory, the stability of the electrospray, whose stiffness is five times stronger under conical confinement, is quantitatively analyzed. The SEF technique enables rapid, continuous production of ≈300 core-shell capsules per second in an aqueous environment, significantly improving cell encapsulation efficiency. This method demonstrates remarkable potential as exemplified in two key applications: (1) a 92-fold increase in human-derived induced pluripotent stem cells (iPSCs) expansion over 10 d, outperforming traditional 2D cultures in both growth rate and pluripotency maintenance, and (2) the development of liver capsules for steatosis modeling, exhibiting normal function and biomimetic lipid accumulation. The SEF-enhanced electrospray method presents a significant advancement in cell encapsulation technology. It offers a more efficient, stable, and biocompatible approach for clinical transplantation, drug screening, and cell therapy.

Mechanically Robust Biopolymer Optical Fibers with Enhanced Performance in the Near-Infrared Region.

Polymer optical fibers (POFs) are lightweight, fatigue-tolerant, and suitable for local area networks, automobiles, aerospace, smart textiles, supercomputers, and servers. However, commercially available POFs are exclusively fabricated using synthetic polymers derived from nonrenewable resources. Recently, attempts have been made to fabricate biocompatible and biopolymeric optical fibers. However, their limitations in mechanical performance, thermal stability, and optical properties foil practical applications in waveguiding. Here, we report a comprehensive study of the preparation of biopolymer optical fibers with tailored mechanical strength, thermal properties, and their short-distance applications. Specifically, we use alginate as one of the key components with methylcelluloses to promote readily scalable wet spinning at ambient conditions to fabricate 21 combinations of composite fibers. The fibers display high maximum strain (up to 58%), Young's modulus (up to 11 GPa), modulus of toughness (up to 63 MJ/m3), and a high strength (up to 195 MPa), depending on the composition and fabrication conditions. The modulus of toughness is comparable to that of glass optical fibers, while the maximum strain is nearly 15 times higher. The mechanically robust fibers with high thermal stability allow rapid humidity, touch sensing, and complex shapes such as serpentine, coil, or twisted structures without losing their light transmission properties. More importantly, the fibers display enhanced optical performance and sensitivity in the near-infrared (NIR) region, making them suitable for advanced biomedical applications. Our work suggests that biobased materials offer innovative solutions to create short-distance optical fibers from fossil fuel-free resources with novel functionalities.

Cellulose-based aerogels, films, and fibers for advanced biomedical applications

Cellulose possesses hydrophilicity, high water retention capacity, excellent mechanical properties, and biocompatibility, making it a promising candidate material for biomedical applications. As a substrate and dispersant used in the preparation of aerogels, films, and fibers, it improves their moisturizing ability, water absorption, drug utilization and slows down the rate of drug release, demonstrating outstanding therapeutic effects in biomedical research. This review summarizes and discusses the latest advancements in the application of cellulose-based aerogels, films, and fibers in the biomedical field. First, the properties of cellulose and its application principles in biomedical materials are analyzed. Second, the methods for preparing cellulose-based aerogels, films, and fibers are summarized, along with their advantages and disadvantages. Then, the latest research progress of cellulose-based aerogels, films, and fibers in drug delivery, wound dressings, and tissue engineering scaffolds is reviewed. Finally, the review concludes with a summary and provides future development directions for the field.

Enzymatic response of heparin-protamine complex: Spectroscopic investigation and application for lung adenocarcinoma cells detection

Though the heparin-protamine complex (HP complex) is a crucial system utilized in clinical settings, the metabolic pathways of this complex remain inadequately understood. Herein, the enzymatic degradation of the heparin-protamine complex by trypsin and its broader implications were investigated. By utilizing fluorescent gold nanoclusters liganded with the HP complex (AuNCs-HP complex), we observed significant morphological and spectral changes during enzymatic degradation. Experiments showed that AuNCs-HP complex could be degraded and cleaved into small fragments by trypsin. Moreover, the AuNCs-HP complex demonstrated its potential as a highly sensitive spectral sensing platform, enabling precise measurement of trypsin activity with an outstanding detection limit (0.34 ng mL−1). Additionally, we explored its utility for specific tumor cell detection, focusing on lung adenocarcinoma cells, and successfully identified their presence through distinctive fluorescence changes. These remarkable findings not only contribute valuable insights into targeted degradation systems but also offer promising opportunities for cancer biomarker detection. The AuNCs-HP complex serves as an innovative tool for real-time trypsin activity monitoring, paving the way for advanced biomedical applications.

High-Specificity Imaging Mass Spectrometry.

Imaging mass spectrometry (IMS) enables highly multiplexed, untargeted tissue mapping for a broad range of molecular classes, facilitating in situ biological discovery. Yet, challenges persist in molecular specificity, which is the ability to discern one molecule from another, and spatial specificity, which is the ability to link untargeted imaging data to specific tissue features. Instrumental developments have dramatically improved IMS spatial resolution, allowing molecular observations to be more readily associated with distinct tissue features across spatial scales, ranging from larger anatomical regions to single cells. High-performance mass analyzers and systems integrating ion mobility technologies are also becoming more prevalent, further improving molecular coverage and the ability to discern chemical identity. This review provides an overview of recent advancements in high-specificity IMS that are providing critical biological context to untargeted molecular imaging, enabling integrated analyses, and addressing advanced biomedical research applications.

The Horizons of Medical Mineralogy: Structure-Bioactivity Relationship and Biomedical Applications of Halloysite Nanoclay.

Medical mineralogy explores the interactions between natural minerals and living organisms such as cells, tissues, and organs and develops therapeutic and diagnostic applications in drug delivery, medical devices, and healthcare materials. Many minerals (especially clays) have been recognized for pharmacological activities and therapeutic potential. Halloysite clay (Chinese medicine name: Chishizhi), manifested as one-dimensional aluminum silicate nanotubes (halloysite nanotubes, HNTs), has gained applications in hemostasis, wound repair, gastrointestinal diseases, tissue engineering, detection and sensing, cosmetics, and daily chemicals formulations. Various biomedical applications of HNTs are derived from hollow tubular structures, high mechanical strength, good biocompatibility, bioactivity, and unique surface characteristics. This natural nanomaterial is safe, abundantly available, and may be processed with environmentally safe green chemistry methods. This review describes the structure and physicochemical properties of HNTs relative to bioactivity. We discuss surface area, porosity and surface defects, hydrophilicity, heterogeneity and charge of external and internal surfaces, as well as biosafety. The paper provides comprehensive guidance for the development of this tubule nanoclay and its advanced biomedical applications for clinical diagnosis and therapy.

Bioengineered Silk Protein-Based 3D In Vitro Models for Tissue Engineering and Drug Development: From Silk Matrix Properties to Biomedical Applications.

3D in vitro model has emerged as a valuable tool for studying tissue development, drug screening, and disease modeling. 3D systems can accurately replicate tissue microstructures and physiological features, mirroring the in vivo microenvironment departing from conventional 2D cell cultures. Various 3D in vitro models utilizing biomacromolecules like collagen and synthetic polymers have been developed to meet diverse research needs andaddress the complex challenges of contemporary research. Silk proteins, bearing structural and functional similarities to collagen, have been increasingly employed to construct advanced 3D in vitro systems, surpassing the limitations of 2D cultures. This review examines silk proteins' composition, structure, properties, and functions, elucidating their role in 3D in vitro models. Furthermore, recent advances in biomedical applications involving silk-based organoid models are discussed. In particular, the unique physiological attributes of silk matrix constituents in in vitro tissue constructs are highlighted, providing a meticulous evaluation of their importance. Additionally, it outlines the current research hurdles and complexities while contemplating future avenues, thereby paving the way for developing complex and biomimetic silk protein-based microtissues.

Fabrication and characterization of multi-layered coaxial agar-based electrospun biocomposite mat, novel replacement for transdermal patches

In the performed study, a novel fabrication of agar-based nanofibers was electrospun in an asymmetric bilayer dressing for biomedical transdermal patches. The optimal parameters for the fabrication of agar-based nanofibers after optimization were a feed rate of 10 μL/min, a 7 cm collector-to-nozzle distance, a 15 kV applied voltage, and a 700-rpm rotating collector speed. Coaxial nanofibers, as a second asymmetric layer, were produced using polyvinyl alcohol (PVA) with cephalexin hydrate, an antibacterial drug, as the core and agar-PCL as the sheath. The morphology of the developed uniaxial and coaxial nanofibrous layers was analysed using a scanning electron microscope and transmission electron microscopy, respectively. For the formation of bilayer asymmetric structures, the agar-PCL uniaxial layer was fabricated over the layer of coaxial PVA and agar-PCL layers for sustained drug release. The agar-based nanofibrous mats exhibited tensile strength of 7 MPa with 40 % elongation failure, 8-fold increased swelling, enhanced wettability (60° contact angle), and a moisture transmission rate of 2174 g/m2/day. The developed coaxial bilayer mats exhibited antimicrobial activity, hemocompatibility, and cytocompatibility. Overall, this novel agar nanofibrous dressing offers promising potential for advanced biomedical applications, particularly as transdermal patches for efficient drug delivery systems.

Glycopolymer with Sulfated Fucose and 6'-Sialyllactose as a Dual-Targeted Inhibitor on Resistant Influenza A Virus Strains.

The frequent mutations of influenza A virus (IAV) have led to an urgent need for the development of innovative antiviral drugs. Glycopolymers offer significant advantages in biomedical applications owing to their biocompatibility and structural diversity. However, the primary challenge lies in the design and synthesis of well-defined glycopolymers to precisely control their biological functionalities. In this study, functional glycopolymers with sulfated fucose and 6'-sialyllactose were successfully synthesized through ring-opening metathesis polymerization and a postmodification strategy. The optimized heteropolymer exhibited simultaneous targeting of hemagglutinin and neuraminidase on the surface of IAV, as evidenced by MU-NANA assay and hemagglutination inhibition data. Antiviral experiments demonstrated that the glycopolymer displayed broad and efficient inhibitory activity against wild-type and mutant strains of H1N1 and H3N2 subtypes in vitro, thereby establishing its potential as a dual-targeted inhibitor for combating IAV resistance.

Chitosan: An overview of biological activities, derivatives, properties, and current advancements in biomedical applications

The second and most often utilized natural polymer is chitosan (CS), a naturally existing amino polysaccharide that is produced by deacetylating chitin. Numerous applications have been the subject of in-depth investigation due to its non-hazardous, biologically compatible, and biodegradable qualities. Chitosan's characteristics, such as mucoadhesion, improved permeability, controlled release of drugs, in situ gelation process, and antibacterial activity, depend on its amino (-NH2) and hydroxyl groups (-OH). This study examines the latest findings in chitosan research, including its characteristics, derivatives, preliminary research, toxic effects, pharmaceutical kinetics and chitosan nanoparticles (CS-NPs) based for non-parenteral delivery of drugs. Chitosan and its derivatives have a wide range of physical and chemical properties that make them highly promising for use in the medicinal and pharmaceutical industries. The characteristics and biological activities of chitosan and its derivative-based nanomaterials for the delivery of drugs, therapeutic gene transfer, delivery of vaccine, engineering tissues, evaluations, and other applications in medicine are highlighted in detail in the current review. Together with the techniques for binding medications to nanoparticles, the application of the nanoparticles was also dictated by their physical properties that were classified and specified. The most recent research investigations on delivery of drugs chitosan nanoparticle-based medication delivery methods applied topically, through the skin, and through the eyes were considered.

4D printing and simulation of body temperature-responsive shape-memory polymers for advanced biomedical applications

Four-dimensional (4D) bioprinting holds significant promise in precision medicine, enabling the emulation of dynamic changes in the human body and tissues to provide personalized treatments. Smart materials for 4D printing (i.e., responsive to specific stimuli) should exhibit properties, such as biodegradability, biocompatibility, and ease of processing, while also enabling the prediction of time-dependent behavior in programmed geometry. This study focused on the development of a body temperature-responsive shape-memory polymer (SMP). The thermal properties of the SMP were analyzed, and its biodegradability and biocompatibility were assessed through structures fabricated by three-dimensional printing techniques. The simulation calculated with this finite element (FE) solution was in good agreement with those measured in experiments. The findings contribute to our understanding of the behavior of SMP under various conditions, validating the effectiveness of the developed material for potential applications in precision medicine and 4D bioprinting. It has the potential for use in medical devices, such as catheters, stents, and artificial scaffolds, prepared by 4D bioprinting.  

New Generation of Osteoinductive and Antimicrobial Polycaprolactone-Based Scaffolds in Bone Tissue Engineering: A Review.

With respect to other fields, bone tissue engineering has significantly expanded in recent years, leading not only to relevant advances in biomedical applications but also to innovative perspectives. Polycaprolactone (PCL), produced in the beginning of the 1930s, is a biocompatible and biodegradable polymer. Due to its mechanical and physicochemical features, as well as being easily shapeable, PCL-based constructs can be produced with different shapes and degradation kinetics. Moreover, due to various development processes, PCL can be made as 3D scaffolds or fibres for bone tissue regeneration applications. This outstanding biopolymer is versatile because it can be modified by adding agents with antimicrobial properties, not only antibiotics/antifungals, but also metal ions or natural compounds. In addition, to ameliorate its osteoproliferative features, it can be blended with calcium phosphates. This review is an overview of the current state of our recent investigation into PCL modifications designed to impair microbial adhesive capability and, in parallel, to allow eukaryotic cell viability and integration, in comparison with previous reviews and excellent research papers. Our recent results demonstrated that the developed 3D constructs had a high interconnected porosity, and the addition of biphasic calcium phosphate improved human cell attachment and proliferation. The incorporation of alternative antimicrobials-for instance, silver and essential oils-at tuneable concentrations counteracted microbial growth and biofilm formation, without affecting eukaryotic cells' viability. Notably, this challenging research area needs the multidisciplinary work of material scientists, biologists, and orthopaedic surgeons to determine the most suitable modifications on biomaterials to design favourable 3D scaffolds based on PCL for the targeted healing of damaged bone tissue.