Biomedical Applications Research Articles

Artificial Polymerizations in Living Organisms for Biomedical Applications

Artificial Polymerizations in Living Organisms for Biomedical Applications

Biomimetic Plasmonic Nanophages by Head/Tail Self-Assembling: Gold Nanoparticle/Virus Interactions.

Gold nanoparticles (AuNPs), because of their dual plasmonic and catalytic functionalities, are among the most promising nanomaterials for the development of therapeutic and diagnostic tools for severe diseases such as cancer and neurodegeneration. Bacteriophages, massively present in human biofluids, are emerging as revolutionary biotechnological tools as they can be engineered to display multiple specific binding moieties, providing effective targeting ability, high stability, low cost, and sustainable production. Coupling AuNPs with phages can lead to an advanced generation of nanotools with great potential for biomedical applications. In the present study, we analyzed the interactions between differently sized AuNPs and filamentous M13 phages, establishing an advanced characterization platform that combines analytical techniques and computational models for an in-depth understanding of these hybrid self-assembling systems. A precise and structurally specific interaction of the AuNP-M13 hybrid complexes was observed, leading to a peculiar head/tail "tadpole-like" configuration. In silico simulations allowed explaining the mechanisms underlying the preferential assembly route and providing information about AuNPs' size-dependent interplay with specific M13 capsid proteins. The AuNP-M13 structures were proven to be biomimetic, eluding the formation of biomolecular corona. By keeping the biological identity of the virion, hybrid nanostructures maintained their natural recognition/targeting ability even in the presence of biomolecular crowding. In addition, we were able to tune the hybrid nanostructures' tropism toward E. coli based on the AuNP size. Overall, our results set the fundamental basis and a standard workflow for the development of phage-based targeting nanotools, valuable for a wide spectrum of nanotechnology applications.

Unpacking the packaged optical fiber bio-sensors: understanding the obstacle for biomedical application

A biosensor is a promising alternative tool for the detection of clinically relevant analytes. Optical fiber as a transducer element in biosensors offers low cost, biocompatibility, and lack of electromagnetic interference. Moreover, due to the miniature size of optical fibers, they have the potential to be used in microfluidic chips and in vivo applications. The number of optical fiber biosensors are extensively growing: they have been developed to detect different analytes ranging from small molecules to whole cells. Yet the widespread applications of optical fiber biosensor have been hindered; one of the reasons is the lack of suitable packaging for their real-life application. In order to translate optical fiber biosensors into clinical practice, a proper embedding of biosensors into medical devices or portable chips is often required. A proper packaging approach is frequently as challenging as the sensor architecture itself. Therefore, this review aims to give an unpack different aspects of the integration of optical fiber biosensors into packaging platforms to bring them closer to actual clinical use. Particularly, the paper discusses how optical fiber sensors are integrated into flow cells, organized into microfluidic chips, inserted into catheters, or otherwise encased in medical devices to meet requirements of the prospective applications.

Advances in silver nanoparticles: a comprehensive review on their potential as antimicrobial agents and their mechanisms of action elucidated by proteomics

Nanoparticles play a crucial role in the field of nanotechnology, offering different properties due to their surface area attributed to their small size. Among them, silver nanoparticles (AgNPs) have attracted significant attention due to their antimicrobial properties, with applications that date back from ancient medicinal practices to contemporary commercial products containing ions or silver nanoparticles. AgNPs possess broad-spectrum biocidal potential against bacteria, fungi, viruses, and Mycobacterium, in addition to exhibiting synergistic effects when combined with certain antibiotics. The mechanisms underlying its antimicrobial action include the generation of oxygen-reactive species, damage to DNA, rupture of bacterial cell membranes and inhibition of protein synthesis. Recent studies have highlighted the effectiveness of AgNPs against various clinically relevant bacterial strains through their potential to combat antibiotic-resistant pathogens. This review investigates the proteomic mechanisms by which AgNPs exert their antimicrobial effects, with a special focus on their activity against planktonic bacteria and in biofilms. Furthermore, it discusses the biomedical applications of AgNPs and their potential non-preparation of antibiotic formulations, also addressing the issue of resistance to antibiotics.

Preparation and Characterization of Hydroxyapatite Based Composite Material via Cold Sintering Process

This study focuses on the synthesis of hydroxyapatite (HA) from bovine bones through calcination and subsequent combination with Polyvinyl Alcohol (PVA) using the Cold Sintering Process (CSP). The CSP, operating at lower temperatures than conventional methods, aims to preserve the bioactivity and biocompatibility of HA, crucial for biomedical applications. The research investigates the influence of HA composition, sintering temperature, and PVA content on the porosity and compressive strength of the HA-PVA composite. The Hydroxyapatite powder, obtained from calcinated bovine bones, exhibits irregular shapes and sizes with a maximum grain size of 10µm, confirmed by SEM analysis. XRD analysis validates the successful production of Hydroxyapatite, showcasing characteristic peaks. The HA/PVA composite's XRD pattern indicates the dominance of HA, with PVA present as well. The study produces 27 specimens through the CSP, varying HA composition and sintering temperature. Porosity increases with higher HA content and sintering temperature, attributed to the role of PVA in binding HA particles. Compressive strength rises with increased HA content, emphasizing HA's role in enhancing mechanical strength. The presence of porosity is mitigated by a strong bond between HA and PVA, contributing to structural integrity. This research provides insights into tailoring HA-PVA materials for biomedical applications, considering controlled porosity and mechanical strength. The CSP, with its unique advantages, emerges as a promising method for developing customized materials to meet diverse biomedical needs.

SYNTHESIS OF MONO-DISPERSE MESOPOROUS SILICA-COATED MAGNETITE NANOPARTICLES FOR BIOSEPARATION

Magnetite nanoparticles (NPs) were synthesized using a cost-effective co-precipitation method. Magnetite NPs were encapsulated with silica via the modified Stober Method. Tetra ethyl ortho silicate (TEOS) was hydrolyzed and condensed with ethanol and H2O solution. Stable and biocompatible NPs were synthesized for biomedical applications such as bioseparation. This study expresses the NPs that can potentially be used in the bioseparation of toxic protein isolations and targeted drug delivery. X-ray diffraction verified the phase pattern having crystals like Fd-3[Formula: see text]m cubic space. Scanning electron microscopy (SEM) images identified the spherical-shaped NPs having size ranges from 15[Formula: see text]nm to 30[Formula: see text]nm for magnetite NPs and 20–40[Formula: see text]nm for silica-coated magnetite NPs. Fourier transform infrared spectroscopy (FTIR) confirmed the bond spectrum peak at 549[Formula: see text][Formula: see text] and 562[Formula: see text][Formula: see text] for magnetite NPs and silica-coated magnetite NPs, respectively. UV–Visible analysis observed the band absorptions above 250[Formula: see text]nm for magnetite and above 300[Formula: see text]nm for silica-coated magnetite NPs. This research suggests an easy way to use silica-coated Magnetite NPs for bioseparation at room temperature.

Zwitterionic Polyelectrolyte Complex Vesicles Assembled from Homopoly(2-Oxazoline)s as Enzyme Catalytic Nanoreactors for Potent Anti-Tumor Efficiency.

Enzymes are known for their remarkable catalytic efficiency across a wide range of applications. Here, we present a novel and convenient nanoreactor platform based on zwitterionic polyelectrolyte complex vesicles (PCVs), assembled from oppositely charged homopoly(2-oxazoline)s, facilitating enzyme immobilization. We show remarkable enhancements in catalytic activity and stability by encapsulation of lipase as a model enzyme. Even as the temperature rises, the performance of the lipase remains robust. Further, the structural characteristics of PCVs, including hollow architecture and semipermeable membranes, endow them with unique advantages for enzyme cascade reactions involving glucose oxidase (GOx) and horseradish peroxidase (HRP). A decline in catalytic efficiency is shown when the enzymes are individually loaded and subsequently mixed, in contrast to the coloaded GOx-HRP-PCV group. We demonstrate that the vesicle structures establish confined environments where precise enzyme-substrate interactions facilitate enhanced catalytic efficiency. In addition, the nanoreactors exhibit excellent biocompatibility and efficient anti-tumor activity, which hold significant promise for biomedical applications within enzyme-based technologies.

A Critical Review of Biodegradable Zinc Alloys toward Clinical Applications.

Biodegradable zinc (Zn) alloys stand out as promising contenders for biomedical applications due to their favorable mechanical properties and appropriate degradation rates, offering the potential to mitigate the risks and expenses associated with secondary surgeries. While current research predominantly centers on the in vitro examination of Zn alloys, notable disparities often emerge between in vivo and in vitro findings. Consequently, conducting in vivo investigations on Zn alloys holds paramount significance in advancing their clinical application. Different element compositions and processing methods decide the mechanical properties and biological performance of Zn alloys, thus affecting their suitability for specific medical applications. This paper presents a comprehensive overview of recent strides in the development of biodegradable Zn alloys, with a focus on key aspects such as mechanical properties, toxicity, animal experiments, biological properties, and molecular mechanisms. By summarizing these advancements, the paper aims to broaden the scope of research directions and enhance the understanding of the clinical applications of biodegradable Zn alloys.

Sulfur Dioxide (SO2) Releasing Polymeric Systems: Design, Synthesis, and Potential Biomedical Applications

Sulfur Dioxide (SO₂) Releasing Polymeric Systems: Design, Synthesis, and Potential Biomedical Applications

Improvement of biological and corrosion behavior of plasma electrolytic oxidized Mg implant by 3D printed scaffold of amine-terminated PEG/PCL loaded with dexamethasone

Although magnesium-based implants have good biocompatibility and biodegradability, they suffer from rapid corrosion in the body environment, which limits their biomedical applications. This study represents an approach for designing a bioactive and anti-corrosive hybrid structure composed of an inorganic layer by plasma electrolytic oxidation process and an organic layer of 3D printed polycaprolactone and amine-terminated polyethylene glycol scaffold containing dexamethasone. The results indicated that the hybrid layer exhibited superior adhesion strength, high corrosion resistance, remarkable biocompatibility, cell attachment, and osteogenic differentiation. The dexamethasone released from the 3D printed scaffold revealed high osteogenic differentiation capability. Hence, the fabrication of plasma electrolytic oxidized interlayer with a 3D printed scaffold can be a novel platform to preserve the magnesium-based biological implants from corrosion and to regenerate bone along with the controlled release of osteogenic components.

Early Detection and Noninvasive Staging of Kidney Dysfunction by a PEGylated Conventional Fluorophore via GFR-Sensitive Renal Transport.

Noninvasive fluorescence imaging of renal function is a valuable technique for understanding kidney disease progression and the development of renal medicine. This technique requires sensitive imaging probes for reporting renal dysfunction accurately at early stage. Herein, a molecularly engineered imaging probe (800CW-PEG45-COOH) was synthesized by simply PEGylating conventional near-infrared fluorophore IRDye800CW with NH2-PEG45-COOH (molecular weight ∼2100 Da) for early detection and staging of renal dysfunction through noninvasive real-time kidney imaging. 800CW-PEG45-COOH not only cleared through the kidney efficiently (>90% injection dosage at 24 h postinjection) but was also found to be freely filtered by glomeruli without renal tubular reabsorption and secretion. Despite this simple construction strategy, the transport of 800CW-PEG45-COOH within the kidneys was extremely sensitive to the alteration of the glomerular filtration rate (GFR), which enabled it to detect renal dysfunction much earlier than commonly used serum biomarkers and stage kidney function impairments (mild vs severe dysfunction) via imaging-based kidney clearance kinetics. This work not only provides a promising optical imaging probe for the noninvasive evaluation of kidney function but also highlights the utility of PEGylation in enhancing the performance of conventional organic dyes in biomedical applications.

Macro-Calcium Carbonate-Hydrogel Hybrid Spheroids: Design and Biomedical Applications.

In advancing tissue engineering, we introduce a particle system combining the strength of calcium carbonate with the flexibility of hydrogels enhanced with alkaline phosphatase (ALP) for improved bone regeneration. Our innovation lies in creating large hybrid macrospheroids by bonding mineral nanostructured microparticles loaded with ALP through hydrogel polymerization. These composite macrospheroids address critical challenges in cell seeding, growth, and handling within three-dimensional (3D) environments. We conducted extensive characterization of these particles using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), mechanical property assessment, and fluorescence microscopy. The results demonstrate that the hybrid macrospheroids significantly enhance cell manipulation and growth in three-dimensional structures. Specifically, ALP-loaded macrospheroids showed a marked improvement in osteogenic activity, promoting effective bone tissue regeneration. This study not only showcases a unique approach to overcoming the limitations of traditional hydrogels in tissue engineering but also opens pathways for bone tissue regeneration. Our findings offer a promising tool for cell seeding and growth in 3D structures, potentially revolutionizing practices in tissue engineering and regenerative medicine.

N2 as an Efficient IR Probe Molecule for the Investigation of Ceria-Containing Materials

Ceria and ceria-based catalysts are very important in redox and acid-base catalysis. Nanoceria have also been found to be important in biomedical applications. To design efficient materials, it is necessary to thoroughly understand the surface chemistry of ceria, and one of the techniques that provides such information about the surface is the vibrational spectroscopy of probe molecules. Although the most commonly used probe is CO, it has some disadvantages when applied to ceria and ceria-based catalysts. CO can easily reduce the material, forming carbonate-like species, and can be disproportionate, thus modifying the surface. Here, we offer a pioneering study of the adsorption of 15N2 at 100 K, demonstrating that dinitrogen can be more advantageous than CO when studying ceria-based materials. As an inert gas, N2 is not able to oxidize or reduce cerium cations and does not form any surface anionic species able to modify the surface. It is infrared and transparent, and thus there is no need to subtract the gas phase spectrum, something that often increases the noise level. Being a weaker base than CO, N2 has a negligible induction effect. By using stoichiometric nano-shaped ceria samples, we concluded that 15N2 can distinguish between surface Ce4+ sites on different, low index planes; with cations on the {110} facets and on some of the edges, Ce4+15N2 species with IR bands at 2258–2257 cm−1 are formed. Bridging species, where one of the N atoms from the molecule interacts with two Ce4+ cations, are formed on the {100} facets (2253–2252 cm−1), while the interaction with the {111} facets is very weak and does not lead to the formation of measurable amounts of complexes. All species are formed by electrostatic interaction and disappear during evacuation at 100 K. In addition, N2 provides more accurate information than CO on the acidity of the different OH groups because it does not change the binding mode of the hydroxyls.

A comprehensive review on Nanoparticle: Characterization, classification, synthesis method, silver nanoparticles and its applications

Nanotechnology offers many advantages in various fields of science. Recent advances in nanotechnology have proven that nanoparticles acquire a great potential in medical applications. Recent advances in nanoscience and nanotechnology radically changed the way we diagnose, treat, and prevent various diseases in all aspects of human life. This present review provided a detailed overview of the synthesis, properties and applications of Nanoparticles (NPs) exist in different forms. NPs are tiny & small, ranges from 1 to 100 nm. They are classified into different classes based on their properties, shapes or sizes. The different groups include fullerenes, metal NPs, ceramic NPs, and polymeric NPs. NPs possess unique physical and chemical properties due to their high surface area and nanoscale size. Silver nanoparticles (AgNPs) are one of the most vital and fascinating nanomaterials among several metallic nanoparticles that are involved in biomedical applications. AgNPs play an important role in nanoscience and nanotechnology, particularly in nanomedicine. The major applications of silver nanoparticles in the medical field include diagnostic applications and therapeutic applications, apart from its antimicrobial activity.

Design and synthesis of a novel chiral photoacoustic probe and accurate imaging detection of hydrogen peroxide in vivo.

Nanocatalytic medicine, which aims to accurately target and effectively treat tumors through intratumoral in situ catalytic reactions triggered by tumor-specific environments or markers, is an emerging technology. However, the relative lack of catalytic activity of nanoenzymes in the tumor microenvironment (TME) has hampered their use in biomedical applications. Therefore, it is crucial to develop a highly sensitive probe that specifically responds to the TME or disease markers in the TME for precision diagnosis and treatment of diseases. In this work, a chiral photoacoustic (PA) nanoprobe (D/L-Ce@MoO3) based on the H2O2-catalyzed TME activation reaction was constructed in a one-step method using D-cysteine (D-Cys) or L-cysteine (L-Cys), polymolybdate, and cerium nitrate as raw materials. The designed and synthesized D/L-Ce@MoO3 chiral nanoprobe can perform in situ, non-invasive, and precise imaging of pharmacological acute liver injury. In vivo and in vitro experiments have shown that the D/L-Ce@MoO3 probe had chiral properties, the CD signal decreased upon reaction with H2O2, and the absorption and PA signals increased with increasing H2O2 concentration. This is because of the catalytic reaction between Ce ions doped in the nanoenzyme and the high expression of H2O2 caused by drug-induced liver injury to produce ·OH, which has a strong oxidizing property to kill tumor cells and destroy the Mo-S bond in the probe, thus converting the chiral probe into an achiral polyoxometalate (POM) with PA signal.

Enhancing the Mechanical Strength and Thermal Stability of Polylactic Acid (PLA) with the Addition of Epoxidized Waste Cooking Oil (EWCO)

Polylactic Acid (PLA) comes from renewable resources, has a reasonable biodegradability rate, and is used in biomedical, food packaging, textiles, and agricultural applications. PLA offers high mechanical strength and the ability to compost, similar to polyethylene terephthalate (PET) and nylon. However, the brittleness of PLA has always limited its usage. Therefore, bio-based plasticizers in the biopolymer matrices can increase flexibility (elasticity), durability, and workability. This study aims to determine the optimal blending ratio for the PLA blended with epoxidized waste cooking oil (EWCO) to enhance the mechanical and thermal properties of PLA/EWCO. The mechanical strength test consists of the hardness test (N/mm<sup>2</sup>), flexural strength (MPa), and impact energy (kJ/m<sup></sup>) adopted to evaluate the plasticizing characteristics. The thermal stability analysis involves glass transition temperature (T<sub>g</sub>) (°C), cold-crystallization temperature (T<sub>cc</sub>) (°C) and melting temperature (T<sub>m</sub>) (°C). The blending ratio is 97.5PLA/2.5EWCO, 95PLA/5EWCO, 92.5PLA/7.5EWCO and 90PLA/10EWCO. As a result, 97.5:2.5 of PLA/EWCO reduces intermolecular interactions by stimulating more free volume in biopolymer chains’ mobility and enhancing the flexibility and elasticity of the PLA blends. Ultimately, the brittleness of PLA decreased with increasing EWCO bio-based plasticizer.

Sustainable and effective reconditioning of SPR gold chips functionalized with molecularly imprinted polynorepinephrine

Surface Plasmon Resonance (SPR) technology has revolutionized the study of affinity-based biomolecular interactions, offering label-free and real-time analysis capabilities. However, traditional SPR gold chips have been viewed as disposable due to challenges in post-use reconditioning, leading to significant resource wastage and increased costs. To address this issue, we propose a novel approach utilizing polynorepinephrine-based (PNE) Molecularly Imprinted Bio-Polymers (MIBPs) as alternative receptors to conventional antibodies. Self-adhesive MIBPs do not require covalent immobilization. This enables efficient and rapid chip functionalization and post-use removal, facilitating multiple reuses of the plasmon source without compromising analytical performance. We conducted a thorough characterization and data analysis, confirming the robustness and repeatability of a single MIBP-functionalized chip for human IgG detection. 10 cycles of reconditioning and reuse, assayed by 60 kinetic calibrations, were performed. Our findings demonstrate the potential indefinite reuse of SPR chips facilitated by PNE MIBPs, with implications for streamlining test development and routine implementation in SPR biosensing applications. Therefore, they represent a sustainable solution to the longstanding challenge of disposable SPR gold chips also by reducing the reliance on animal-derived Abs for bioanalytic testing. Being also extremely low-cost and green, PNE-based MIBPs minimize the ecological footprint associated with traditional SPR assays. Overall, our work represents a significant advancement towards the development of reusable SPR biosensors. It promises a more sustainable and cost-effective future for biomedical research and diagnostic applications, with application on other transducers and bioanalytical platforms.

Therapeutic efficacy of Strobilanthes urticifolia-infused pectin/polyacrylic acid hydrogel for targeted hepatorenal fibrosis mitigation: A multifaceted biomaterial approach.

Pectin/polyacrylic acid (PPAA) hydrogel is a unique and versatile biomaterial with applications in drug delivery, wound healing, tissue engineering, and agriculture, owing to its tailored properties and multifunctional attributes. This study aims to harness the therapeutic potential of Strobilanthes urticifolia extract within a PPAA hydrogel matrix to attenuate liver and kidney fibrosis through targeted and sustained delivery of biologically active substances. PPAA hydrogel was prepared by free radical polymerization, followed by its porosity and swelling determination. The results depicted the porous nature of PPAA hydrogel and improved swelling properties at pH 7.4, confirming its drug delivery promise. The polyphenolic-enriched S. urticifolia extracts of leaf and flower were loaded onto PPAA hydrogel, and the loading efficiency was 87% (leaf) and 62.5% (flower). Moreover, slow-release studies showed controlled and prolonged release of polyphenols for 7 days. The polyphenolic-enriched hydrogel's microstructure was characterized using SEM, FTIR, and thermogravimetric analysis (TGA). SEM results revealed a highly porous structure of polyphenol enriched PPAA hydrogel, while FTIR analysis confirmed the presence of functional groups such as OH group of carboxylic acid, aliphatic CH2 stretching due to acrylic acid grafting with pectin, CO stretching due to acid linkage with pectin, CH of aromatic ring, and CH of carboxylate salt in PPAA hydrogel. TGA of PPAA hydrogel showed its stability up to 488°C. Additionally, the S. urticifolia extract loaded PPAA hydrogel displayed significant antibacterial properties and minimum inhibitory concentrations against both Gram-positive and Gram-negative bacteria. In vivo studies carried out on rats demonstrated that polyphenolic enriched PPAA hydrogel significantly attenuates liver and kidney fibrosis. Therefore, it is concluded from the present study that loading of polyphenolic enriched extract from leaves and flower of S. urticifolia enhanced the biomedical applications of PPAA hydrogel. RESEARCH HIGHLIGHTS: The PPAA hydrogel developed in this study exhibits a highly porous structure and improved swelling properties at physiological pH (7.4), making it an excellent candidate for drug delivery systems. S. urticifolia extracts, rich in polyphenols, were successfully incorporated into the PPAA hydrogel with high loading efficiencies of 87% for leaf and 62.5% for flower extracts. Loading of polyphenolic enriched extracts of S. urticifolia onto PPAA enhanced its biological activities such as antibacterial, hepatoprotective, and reno-protective activities as depicted by in vitro and in vivo studies.

Sulfated Alginate for Biomedical Applications.

Alginate (Alg) polymers have received much attention due to the mild conditions required for gel formation and their good bio-acceptability. However, due to limited interactions with cells, many drugs, and biomolecules, chemically modified alginates are of great interest. Sulfated alginate (S-Alg) is a promising heparin-mimetic that continues to be investigated both as a drug molecule and as a component of biomaterials. Herein, the S-Alg literature of the past five years (2017-2023) is reviewed. Several methods used to synthesize S-Alg are described, with a focus on new advances in characterization and stereoselectivity. Material fabrication is another focus and spans bulk materials, particles, scaffolds, coatings, and part of multicomponent biomaterials. The new application of S-Alg as an antitumor agent is highlighted together with studies evaluating safety and biodistribution. The high binding affinity of S-Alg for various drugs and heparin-binding proteins is exploited extensively in biomaterial design to tune the encapsulation and release of these agents and this aspect is covered in detail. Recommondations include publishing key material properties to allow reproducibility, careful selection of appropriate sulfation strategies, the use of cross-linking strategies other than ionic cross-linking for material fabrication, and more detailed toxicity and biodistribution studies to inform future work.

Biosynthesized Graphene Oxide Nanoparticles: In-Vitro Comparative Study for Biomedical Applications

Biosynthesized Graphene Oxide Nanoparticles: In-Vitro Comparative Study for Biomedical Applications