Use Of Biomaterials Research Articles

An Aged Tree with a New Bloom: A Simple Spatiotemporal Programming Strategy Enables Carbon Dot Photosensitizers to Regulate Cell Pyroptosis for Enhanced Tumor Photodynamic-Immunotherapy.

Pyroptosis induced by photodynamic therapy (PDT) is a promising field in both PDT and immunotherapy for tumors. However, effectively inducing tumor cell pyroptosis while triggering a strong immune response using current photosensitizers remains challenging. Herein, the developed positively charged carbon dots (PCDs) nanoPSs were utilized to modulate tumor cell pyroptosis for the first time through a simple spatiotemporal programming strategy. Briefly, PCDs enabled precisely time-dependent targeting of the cell membrane or lysosome. Upon light irradiation, in vitro studies revealed that lysosome-targeted PDT primarily induced apoptosis, while membrane-targeted PDT triggered pyroptosis, resulting in enhanced PDT efficacy and robust activation of the immune response. Conclusively, in vivo studies demonstrated that PCDs could serve as a novel pyroptosis nanotuner for enhanced photodynamic-immunotherapy, thereby simultaneously eliminating primary tumors and inhibiting distant tumor growth and metastases. This spatiotemporal programming strategy unprecedentedly offers a rejuvenation of aged PSs and expands the biomedical use of CDs in immunotherapy.

Advanced functional polymer materials for biomedical applications

AbstractPolymer structures are essential in biomedical applications due to their biocompatibility, biodegradability, and ability to form intricate structures on micro‐ to nanometer scales. This review, emphasizing electrospinning and phase inversion techniques, examines the fabrication strategies and chemical design of polymer structures for biomedical use. Electrospinning, particularly needleless electrospinning, produces nanofibres with high porosity and flexibility and is widely applied in tissue engineering and drug delivery. Phase inversion, including thermal, nonsolvent‐, vapor‐ and evaporation‐induced phase separation, allows precise control over polymer properties but faces challenges in terms of cooling rates and solvent characteristics. Chemical design through doping, functionalization, cross‐linking and copolymerization enhances the biocompatibility, biodegradability and mechanical properties of polymers, facilitating advanced applications in drug delivery, tissue scaffolding and biosensors. Advanced functional polymers are revolutionizing biomedical fields, offering innovative solutions for therapeutic medicine delivery, disease detection, diagnostics, and regenerative medicine. Despite remarkable progress, challenges, such as scalability, cost‐effectiveness, and environmental impact, persist. This review underscores the transformative potential of advanced polymer materials in medical treatments and advocates for continuous research and interdisciplinary collaboration to overcome existing challenges and fully exploit the capabilities of these materials in improving patient care and medical outcomes. Future perspectives highlight enhancing precision control mechanisms, integrating phase inversion with other techniques and developing large‐scale production methods to advance the field further.

Synthesis of dumbbell-like heteronanostructures encapsulated in ferritin protein: Towards multifunctional protein based opto-magnetic nanomaterials for biomedical theranostic

Dumbbell-like hetero nanostructures based on gold and iron oxides is a promising material for biomedical applications, useful as versatile theranostic agents due the synergistic effect of their optical and magnetic properties. However, achieving precise control on their morphology, size dispersion, colloidal stability, biocompatibility and cell targeting remains as a current challenge. In this study, we address this challenge by employing biomimetic routes, using ferritin protein nanocages as template for these nanoparticles’ synthesis. We present the development of an opto-magnetic nanostructures using the ferritin protein, wherein gold and iron oxide nanostructures were produced within its cavity. Initially, we investigated the synthesis of gold nanostructures within the protein, generating clusters and plasmonic nanoparticles. Subsequently, we optimized the conditions for the superparamagnetic nanoparticles synthesis through controlled iron oxidation, thereby enhancing the magnetic properties of the resulting system. Finally, we produce magnetic nanoparticles in the protein with gold clusters, achieving the coexistence of both nanostructures within a single protein molecule, a novel material unprecedented to date. We observed that factors such as temperature, metal/protein ratios, pH, dialysis, and purification processes all have an impact on protein recovery, loading efficiency, morphology, and nanoparticle size. Our findings highlight the development of ferritin-based nanomaterials as versatile platforms for potential biomedical use as multifunctional theranostic agents.

Polymer-Based Optical Guided-Wave Biomedical Sensing: From Principles to Applications

Polymer-based optical sensors represent a transformative advancement in biomedical diagnostics and monitoring due to their unique properties of flexibility, biocompatibility, and selective responsiveness. This review provides a comprehensive overview of polymer-based optical sensors, covering the fundamental operational principles, key insights of various polymer-based optical sensors, and the considerable impact of polymer integration on their functional capabilities. Primary attention is given to all-polymer optical fibers and polymer-coated optical fibers, emphasizing their significant role in “enabling” biomedical sensing applications. Unlike existing reviews focused on specific polymer types and optical sensor methods for biomedical use, this review highlights the substantial impact of polymers as functional materials and transducers in enhancing the performance and applicability of various biomedical optical sensing technologies. Various sensor configurations based on waveguides, luminescence, surface plasmon resonance, and diverse types of polymer optical fibers have been discussed, along with pertinent examples, in biomedical applications. This review highlights the use of biocompatible, hydrophilic, stimuli-responsive polymers and other such functional polymers that impart selectivity, sensitivity, and stability, improving interactions with biological parameters. Various fabrication techniques for polymer coatings are also explored, highlighting their advantages and disadvantages. Special emphasis is given to polymer-coated optical fiber sensors for biomedical catheters and guidewires. By synthesizing the latest research, this review aims to provide insights into polymer-based optical sensors’ current capabilities and future potential in improving diagnostic and therapeutic outcomes in the biomedical field.

Comprehensive evaluation of the nephrotoxicity of carbon quantum dots: Effects of the surface charge

Carbon quantum dots (CQDs) are garnering attention for their broad applications. This study offers a detailed evaluation of the biomedical safety and health risks of carbon quantum dots (CQDs) with different surface modifications, addressing a key gap in their safe application. It focuses on three CQD types: diammonium citrate-based (CQDs-A), spermidine trihydrochloride-based (CQDs-S), and a combination (CQDs-A/S), analyzing their physicochemical properties, cytotoxicity, oxidative stress, inflammatory responses, and nephrotoxicity. While all CQDs were under 10 nm, their biological impacts varied. Positively charged CQDs-S and CQDs-A/S showed significant cytotoxicity in HEK293 cells, inducing oxidative stress but not activating NLRP3 inflammasome, indicating a limited inflammatory response. Renal integrity remained unaffected, with stable zonula occludens 2 expression and unaltered renal markers. In vivo studies in BALB/c mice further supported the safety of CQDs, showing no organ damage or kidney pathology at high doses. The findings underscore the potential for safe biomedical use of CQDs, particularly when their retention time is minimized. This research makes a novel contribution by linking CQDs' surface charge to cytotoxic effects and oxidative stress, providing key insights into their safe use in biomedicine and filling a critical gap in nanoparticle toxicity studies.

Curcumin-loaded lignin nanoparticles: Exploring sonication effects on drug loading and particle properties for future biomedical use

The present study investigates the effects of sonication and cross-linker (oxalic acid) concentration on drug loading and the properties of curcumin-loaded lignin nanoparticles. Selected samples were further assessed for their toxicity and antioxidant potential using the eukaryotic model organism Saccharomyces cerevisiae. Transmission electron microscopy analyses revealed the formation of spherical nanoparticles with diameters in the range of 39–49 nm. Differential scanning calorimetry experiments confirmed the encapsulation of curcumin. Factorial experimental design analyses indicated that sonication time, wave amplitude, cross-linker concentration, and their interactions significantly influenced both ζ-potential – from (−37.0 ± 1.7) mV to (−48.4 ± 0.6) mV – and curcumin loading – from (3.70 ± 0.32) % to (7.10 ± 0.57) %. These parameters are critical for biomedical applications as they relate to the clearance of nanoparticles from the human bloodstream and drug dosage optimization. Although sonication has been previously reported for the preparation of lignin nanoparticles, this study represents the first documented instance of manipulating drug loading by controlled sonication parameters. While none of the investigated factors significantly affected the mean particle diameter, observations from TEM micrographs suggest that cross-linker concentration and wave amplitude notably influence nanoparticle morphology. Moreover, the curcumin-loaded nanoparticles exhibited non-toxicity toward Saccharomyces cerevisiae and demonstrated the ability to enhance yeast cell tolerance to H2O2-induced oxidative stress, underscoring their antioxidant potential. Therefore, this research significantly contributes to the scientific understanding of how the control of sonication parameters and cross-linkers can modulate the properties of curcumin-loaded lignin nanoparticles for future biomedical applications.

Advances in Mesoporous Silica Nanoparticles: Synthesis, Characterization, and Biomedical Uses

Mesoporous silica nanoparticles (MSNs) have drawn significant attention due to their exceptional properties and diverse range of applications, particularly in nanomedicine. The distinctive properties of MSNs, such as their high surface area, tunable pore size, and versatile surface chemistry, make them ideal candidates for various biomedical applications. This review aims to present a detailed understanding of MSNs, from synthesis and characterization to their versatile applications in biomedicine, highlighting their significant potential in advancing healthcare technologies. The synthesis methods for MSNs were comprehensively discussed, emphasizing the influence of parameters like solvent, base, alkoxysilane concentrations, and template surfactants on the size and shape of the nanostructures. Different types of MSNs, including MCM-41, SBA-15, KIT-6, and hollow MSNs, are discussed, along with their synthesis protocols and unique characteristics. The review also covers various spectroscopic techniques, such as XRD, XPS, FTIR, NMR, and fluorescence spectroscopy, which are crucial for characterizing MSNs. Furthermore, the biomedical applications of MSNs are highlighted, demonstrating their potential in drug delivery systems, imaging, and diagnostics. The review concludes with a discussion of the future perspectives and challenges in the field, providing insights into potential developments and the prospects for clinical translation.

Regioselective sulfation of alginate at 2-O-position of mannuronic acid unit with Py∙SO3 in DMSO

Alginates are brown algal polysaccharides consisting of β-D-mannuronic (M) and α-l-guluronic acid (G) residues linked with 1→4 glycosidic bonds. To functionalize these natural resources for biomedical use, alginates can be chemically modified, including by sulfation. Here regioselective sulfation of alginates at M-2 in DMSO with Py∙SO3 is described, by either sulfating alginates directly or through using alginates with added protecting groups (PG-s), including TBDMS-ether, Piv-, Bz-esters and intramolecular 3,6-lactone. Highest regioselectivity was found by sulfating TBDMS- and Piv-protected alginates, with over 65 % of M-residues being 2-O-sulfated. However significant reduction in molecular weight was found when alginates were sulfated in DMSO. Results from this work will allow a degree of control over substitution patterns in sulfated alginates. This will allow to more accurately determine structure-property relationships in biomedical research.

Medical Applications and Cellular Mechanisms of Action of Carboxymethyl Chitosan Hydrogels.

Carboxymethyl chitosan (CMCS) hydrogels have been investigated in biomedical research because of their versatile properties that make them suitable for various medical applications. Key properties that are especially valuable for biomedical use include biocompatibility, tailored solid-like mechanical characteristics, biodegradability, antibacterial activity, moisture retention, and pH stimuli-sensitive swelling. These features offer advantages such as enhanced healing, promotion of granulation tissue formation, and facilitation of neutrophil migration. As a result, CMCS hydrogels are favorable materials for applications in biopharmaceuticals, drug delivery systems, wound healing, tissue engineering, and more. Understanding the interactions between CMCS hydrogels and biological systems, with a focus on their influence on cellular behavior, is crucial for leveraging their versatility. Because of the constantly growing interest in chitosan and its derivative hydrogels in biomedical research and applications, the present review aims to provide updated insights into the potential medical applications of CMCS based on recent findings. Additionally, we comprehensively elucidated the cellular mechanisms underlying the actions of these hydrogels in medical settings. In summary, this paper recapitulates valuable data gathered from the current literature, offering perspectives for further development and utilization of carboxymethyl hydrogels in various medical contexts.

Structure and mechanisms of stabilization of cytokines EMAP II and AIMP1/p43 in complexes with ligands for biomedical use

Structure and mechanisms of stabilization of cytokines EMAP II and AIMP1/p43 in complexes with ligands for biomedical use

Therapeutic Polymer Hydrogels for Biomedical Use: A Short Review of Critical Conclusions

Therapeutic Polymer Hydrogels for Biomedical Use: A Short Review of Critical Conclusions

(Invited) Nanofluidic Ion Transport in Carbon Nanotube Porin Channels

Extreme spatial confinement in narrow fluidic channels strongly influences their transport properties and enables unconventional selectivity mechanisms that can often mimic some of the selectivity and transport characteristics of biological membrane channels. More than any modern nanomaterial, carbon nanotubes have enabled experimental platforms that can recreate such extreme confinement in a channel with defined geometry and controllable electronic properties. I will discuss ion transport in canon nanotube porin channels and show how confinement phenomena, coupled with the different electronic effects in these channels can shape their transport properties and ion selectivity characteristics. Overall, these observations contribute to our understanding of nanoscale transport and pave the way for developing a new generation of precision separation platforms for biomedical and industrial use.

Synthesis of ZnO nanoparticles from the medicinal plant Salvia fruticosa Mill.: Green approach for potential biomedical application against Zn deficiency in humans

We hypothesized that we could prepare ZnO nanoparticles (ZnO NPs) as a biomedical application treatment of zinc deficiency in human populations. In this study, we report a formulation prepared using a low-cost method for the green synthesis of ZnO NPs by utilizing the medicinal species Salvia fruticosa as natural raw material and Zn(NO3)2∙6H2O as a Zn source. The final product was identified and characterized by elemental analysis using X-ray energy-scattering spectroscopy (EDS), ultraviolet–visible spectroscopy (UV-VIS Spectroscopy), X-ray powder diffraction (XRD), and morphometric analysis using scanning electron microscopy (SEM). Finally, crystallization was studied using transmission electron microscopy (TEM). Afterward, ZnO NPs thus produced were utilized for foliar spraying on S. fruticosa open cultures, and Zn fortification in the foliage. Then, their effects on the biosynthesis of essential oils, and Zn bioavailability to humans were studied through different modes of consumption.ZnO NPs produced using our method were spherical while some were hexagonal, with an average size of approximately 22 nm, based on XRD results. The green synthesis method devised in this study afforded ZnO NPs from Zn(NO3)2∙6H2O with a 95 % yield, and consequently yielded economic benefits with respect to the current market prices. Foliage Zn fortification and the desired features were successfully achieved using ZnO NPs, and the proper mode of consumption of this medicinal plant has been recommended in this study.In conclusion, the methodology described in this study enables eco-friendly green synthesis of ZnO NPs at a low cost using S. fruticosa and puts forward a contemporary and integrated biomedical use of ZnO NPs to treat disorders resulting from or related to Zn deficiency.

Laser processing effects on Ti−45Nb alloy surface, corrosive and biocompatible properties

The Ti−45Nb (wt.%) alloy properties were investigated in relation to its potential biomedical use. Laser surface modification was utilized to improve its performance in biological systems. As a result of the laser treatment, (Ti,Nb)O scale was formed and various morphological features appeared on the alloy surface. The electrochemical behavior of Ti−45Nb alloy in simulated body conditions was evaluated and showed that the alloy was highly resistant to corrosion deterioration regardless of additional laser surface modification treatment. Nevertheless, the improved corrosion resistance after laser treatment was evident (the corrosion current density of the alloy before laser irradiation was 2.84×10−8 A/cm2, while that after laser treatment with 5 mJ was 0.65×10−8 A/cm2) and ascribed to the rapid formation of a complex and passivating bi-modal surface oxide layer. Alloy cytotoxicity and effects of the Ti−45Nb alloy laser surface modification on the MRC-5 cell viability, morphology, and proliferation were also investigated. The Ti−45Nb alloy showed no cytotoxic effect. Moreover, cells showed improved viability and adherence to the alloy surface after the laser irradiation treatment. The highest average cell viability of 115.37% was attained for the alloy laser-irradiated with 15 mJ. Results showed that the laser surface modification can be successfully utilized to significantly improve alloy performance in a biological environment.

Modeling hydration of graphene oxide (GO) – Does size matter?

The biomedical applications of graphene-based materials become one of hot scientific and technological topics in the last few years. Flake graphene oxide (GO) is considered as one of the promising materials for biomedical use due to a number of specific properties, in particular in design of advanced drug delivery systems (DDS). The key factor in the formation of non-covalently bonded complexes for drug transport is the strength of non-covalent interactions of the carrier with both the drug and the environment. In the current work, we have focused on molecular modeling of solvation of zigzag-edged graphene oxide, functionalized with hydroxyl and carboxyl substituents. The hydration was determined from the magnitude of weak intermolecular interactions of GO with one or two water molecules. Our goal was to establish the dependence of the degree and type of functionalization, as well as the size of graphene flakes and the position of hydrophilic substituents on the number and strength of H-bonds. All calculations were performed using density functional theory (DFT) at the B3LYPD3BJ/6-311++G** level. The effect of water solvent was established using an explicit (discrete) model of solvent.

A novel approach for nanobubble generation toward biomedical applications

The stability of free-standing nanobubbles is a long-standing controversial problem due to the Laplace pressure catastrophe at the nanoscale. In most industrial circumstances, a large quantity of surfactants is required as stabilisers or emulsifiers to generate stable bubbles or foams. However, when surfactants exceed a certain level, they can adversely affect living organisms and pose environmental risks. Towards biomedical use, we investigated nanobubble generation through a mini-extruder in amino acid solutions. Herein, we considered glycine (having two acid dissociation constants, i.e. pKa values) and lysine (having three pKa values) as two model amino acids, conducting experiments with various concentrations (0.1 M, 0.5 M and 1 M), along with different pH values (above, equal to, and below the isoelectric points of each amino acids; 5.97 for glycine and 9.74 for lysine). Our results showcased the proof of concept that amino acids can stabilise nanobubbles in bulk for a few days. We achieved remarkable products of nanobubbles via nanopores by extrusion, with reproducible size distribution and stability. We also compared the extrusion protocol with the commonly used ultrasound method. It turned out that extrusion generated samples with smaller sizes and higher concentrations than sonication. This study provides a reliable protocol for generating small-scale nanobubbles for biomedical use, showing great potential in drug delivery for medical treatment.

Anticancer efficacy of biosynthesized silver nanoparticles loaded with recombinant truncated parasporin-2 protein

Bacterial toxins have received a great deal of attention in the development of cancer treatments. Parasporin-2 (PS2Aa1 or Mpp46Aa1) is a Bacillus thuringiensis parasporal protein that preferentially destroys human cancer cells while not harming normal cells, making it a promising anticancer treatment. With the efficient development and sustainable silver nanoparticles (AgNPs) synthesis technology, the biomedical use of AgNPs has expanded. This study presents the development of a novel nanotoxin composed of biosynthesized silver nanoparticles loaded with the N-terminal truncated PS2Aa1 toxin. MOEAgNPs were synthesized using a biological method, with Moringa oleifera leaf extract and maltose serving as reducing and capping agents. The phytochemicals present in M. oleifera leaf extract were identified by GC–MS analysis. MOEAgNPs were loaded with N-terminal truncated PS2Aa1 fused with maltose-binding protein (MBP-tPS2) to formulate PS2-MOEAgNPs. The PS2-MOEAgNPs were evaluated for size, stability, toxin loading efficacy, and cytotoxicity. PS2-MOEAgNPs demonstrated dose-dependent cytotoxicity against the T-cell leukemia MOLT-4 and Jurkat cell lines but had little effect on the Hs68 fibroblast or normal cell line. Altogether, the current study provides robust evidence that PS2-MOEAgNPs can efficiently inhibit the proliferation of T-cell leukemia cells, thereby suggesting their potential as an alternative to traditional anticancer treatments.

Anti-tumoral Immunity and Chemo-preventive Effectiveness of Herbal Extracts of Curcumin, Ginger, Clove and Amygdaline in Ehrlich Ascites Carcinoma-Challenging Mice.

Due to its systemic toxicity, traditional chemotherapy of tumors is being taken into consideration. Herbal therapy, containing phytochemical polyphenol derivatives such as Curcumin (Cur), Ginger (Gin), Cloves (Clov) and Amygdaline (Amyg), is one of the numerous complementary and alternative approaches as an anti-cancer therapy and holds great promise for cancer chemo-prevention with fewer side effects. The current study was designated to assess anti-tumoral immunity and anti-cancer and chemo-preventive effectiveness of herbal extracts of Cur, Ginger, Clov and Amyg in Ehrlich Ascites Carcinoma (EAC)-challenging mice. Chemo-preventive efficacy of herbal extracts of Cur, Gin, Clov and Amyg were analyzed in vivo by examination of the apoptosis rate of EAC tumor cells by flow cytometry. The total numbers of EAC cells, splenocytes counts and leucocytes count with their differentials relative % in peripheral blood (PB) of EACchallenging mice were investigated. EAC-challenging mice treated with herbal extracts of Cur, Gin, Clov and Amyg showed a marked decline in EAC tumor cell count and a noticeable increase in apoptosis rate of EAC tumor cells, a remarkable decrease in serum level of cancer antigen 125 (CA-125) with an obvious increase in the number of splenocytes comparing to that in EAC-challenging mice treated with PBS alone. Moreover, the data indicated an insignificant change in the total leucocytes count and their differentials relative % of eosinophil, neutrophils, monocytes and lymphocytes in EAC-challenging mice treated with Cur and Amyg, but these parameters were markedly increased in EAC-challenging mice injected with Gin and Clov compared to that in EAC-challenging mice treated with PBS alone. To conclude, the herbal extracts of Cur, Gin, Clov and Amyg may have anti-tumoral immunity and anti-cancer potency and potential to reduce the resistance to cancer conventional chemotherapy and exert cancer chemo-protective approaches with low adverse effects. Further research is necessary to determine the regimen's toxicity on various tissues and organs and to connect the diagnostic and therapeutic approaches used in the regimen's biomedical use.

Tuning the photophysical properties of cyanine by barbiturate functionalization and nanoformulation for efficient optoacoustics- guided phototherapy

Cyanine derivatives are organic dyes widely used for optical imaging. However, their potential in longitudinal optoacoustic imaging and photothermal therapy remains limited due to challenges such as poor chemical stability, poor photostability, and low photothermal conversion. In this study, we present a new structural modification for cyanine dyes by introducing a strongly electron-withdrawing group (barbiturate), resulting in a new series of barbiturate-cyanine dyes (BC810, BC885, and BC1010) with suppressed fluorescence and enhanced stability. Furthermore, the introduction of BC1010 into block copolymers (PEG114-b-PCL60) induces aggregation-caused quenching, further boosting the photothermal performance. The photophysical properties of nanoparticles (BC1010-NPs) include their remarkably broad absorption range from 900 to 1200 nm for optoacoustic imaging, allowing imaging applications in NIR-I and NIR-II windows. The combined effect of these strategies, including improved photostability, enhanced nonradiative relaxation, and aggregation-caused quenching, enables the detection of optoacoustic signals with high sensitivity and effective photothermal treatment of in vivo tumor models when BC1010-NPs are administered before irradiation with a 1064 nm laser. This research introduces a barbiturate-functionalized cyanine derivative with optimal properties for efficient optoacoustics-guided theranostic applications. This new compound holds significant potential for biomedical use, facilitating advancements in optoacoustic-guided diagnostic and therapeutic approaches.

Selective delivery of neuropeptide Y peptides linked to magnetic particles for hyperthermia application

Although standard treatments against cancer have achieved significant effects in growth inhibition and tumor elimination, they still cause severe side effects. Therefore, the specific targeting of cancer cells without affecting healthy tissue is currently an important desire in cancer therapy. Cell surface receptors that bind peptides are often overexpressed on tumor cells and can therefore be considered promising targets for selective tumor therapy. Here, we report on the use of neuropeptide Y receptor 1 (Y1R) specific delivery of magnetic nanoparticles. The Y1R is overexpressed in breast cancer cells including triple negative type tumors. Magnetic particles allow for hyperthermia applications for the treatment of malignant cells and have been proposed for biomedical use for several years. One of the limitations so far was selectivity and intracellular uptake into tumor cells. By using specifically modified nanoparticles and site-specific conjugation to selective peptides specific uptake into Y1R positive cells is demonstrated here.