Introduction

The development/application of novel drug delivery systems capable of precisely controlling the delivery of their payloads is an area of intense current research interest as the importance of personalized medicine has been understood. Such systems potentially enable spatiotemporally controlled delivery, for example, maintaining a therapeutically effective level of a drug, minimizing unwanted side effects, and thereby enhancing treatment efficiency. Stimuli-responsive materials (SRMs) have significant potential for the development of smart biomaterials capable of drug delivery with defined release profiles. We are interested in the design, synthesis, and characterization of biomaterials capable of responding to one or more stimuli, and their use in various paradigms.

Methods

An interdisciplinary approach combining chemistry (synthesis), materials science and engineering was employed to prepare and characterize SRMs and their composites (e.g., mechanics, microscopy and spectroscopy). SRMs and their composites were exposed to stimuli (electricity, light and magnetism), and the release profiles of their payloads (e.g., drugs) was quantified spectroscopically.

Results

Electricity, light and magnetism are capable of triggering the delivery of drugs or biologics of various molecular weights from SRMs and their composites in vitro and ex vivo as demonstrated spectroscopically.

Conclusion

SRMs can deliver a variety of clinically relevant payloads of various molecular weights in response to triggers, and can potentially be used to control the chronopharmacology of their payloads in line with the chronobiology of the condition needing treatment. The bioactivities of the bioactive molecules includes anti-microbial, anti-cancer, anti-inflammatory and growth factors. The stimulation paradigms are either designed to be adaptable to integration in existing medical devices or technologies (e.g., catheter balloons inserted via minimally invasive surgery, medical electronics such as bionic eyes, cochlear implants, electrodes for deep brain stimulation, etc.).

In recent years, phytosynthesis of metallic nanoparticles using aqueous extracts of plants and plant products has become considerably important in biomedical and environmental applications due to its non-toxicity and the fact that it is an environmentally friendly approach.

In this study, we developed stable silver nanoparticles using the peels of mangosteen fruit. This fruit peel contains several phytochemicals including flavonoids and polyphenols (phenolic compounds). These phytochemicals possess anti-aging, antioxidant and cytoprotective properties. The formation of nanoparticles was confirmed by the characteristic surface plasmon resonance peak at around 400 nm.

The synthesized nanoparticles were encapsulated in sodium alginate beads with a single-step method via ionotropic crosslinking using calcium chloride (5 wt%). The resulting beads were compact and porous. The photocatalytic properties of the beads were evaluated using various toxic dyes such as Congo red, methylene blue, Alizarin yellow and methyl orange both in the presence and absence of solar radiation.

The nanoclusters acted as catalytic sites for the degradation process, while alginate provided a stable matrix for the immobilization of the nanoclusters and facilitated the mass transfer of the pollutants to the catalytic sites. The study highlights the effectiveness of silver-nanocluster-loaded alginate beads as a promising and eco-friendly material for the treatment of medical waste and contaminated water in the future.

1. Introduction & Significance

Nanoparticles are small particles that range in nanoscale less than 100 nm, which is equivalent to one billionth 10^{-9 1}. The development of nanoparticles by green methods has gained considerable research attention in medical applications such as cancer therapy, tissue engineering, and target-specific drug delivery due to their non-toxicity, surface functionality, and stability. This approach reduces environmental pollution and provides benign materials with desired properties (antibacterial, antibiofilm, antimalarial, and anticancer) for advanced biomedical applications. Palm trees are rich in polyphenols, which can act as both reducing and stabilizing agents ².

2. Methods

In this study, silver and selenium nanoparticles were synthesized using a variety of local palm tree waste and products such as date palm leaves, date buds, and homemade date syrup. The formation of nanoparticles was confirmed by measuring the surface plasmon resonance peak using a UV-VIS spectrophotometer. The antibacterial properties of the silver nanoparticles on three different types of bacteria were studied using the Hinton–Broth method.

3. Results

UV-Vis Spectroscopy confirmed the presence of nanoparticles in all prepared solutions. Additionally, the antibacterial effect was assessed using the disc diffusion method. The greatest antibacterial activity was seen against Escherichia coli, which was evidenced by the large clear zone of inhibition. Moreover, the growth of Staphylococcus aureus was disturbed by the silver nanoparticles.

4. Conclusion

Using palm leaves, buds, and date syrup, a successful synthesis of silver, selenium, and gold nanoparticles was achieved. Bacterial studies showed disruption of bacterial growth in Gram-positive staphylococcus aureus and significant antibacterial effect against Gram-negative Escherichia coli. Next, we aim to examine the effect of the synthesized nanoparticles on cancer cell lines and fibroblasts as well as investigate their ability to enhance wound healing stimuli response using hydrogels. Material sustainability and the conversion of waste to advanced materials were successfully demonstrated in this project.

Introduction: Approximately 40% of nosocomial infections are catheter-associated urinary tract infections. Various surface modification methods are under consideration, with the potential to prevent bacterial colonization on the urinary catheter (UC). Objectives: Herein, we aimed to coat the UC with a coating of polyvinyl alcohol (PVA) and ε-polylysine (PLL) and to check their antimicrobial effects against Staphylococcus aureus. Methodology: A 10% PVA solution was prepared by mixing 10g of PVA in 90 ml deionized water and stirring at 90 °C for two hours. Subsequently, 0.15 ml of 2% glutaraldehyde was added to the PVA solution. Next, the 20 ml of PVA/GA solution was shifted to small beakers to prepare PVA/GA/ε-PL solution in different ratios such as 1ml ε-PL (PVA/GA/ε-PL-1), 0.75 ml ε-PL (PVA/GA/ε-PL-2), 0. 5ml ε-PL (PVA/GA/ε-PL-3), 0. 25ml ε-PL (PVA/GA/ε-PL-4). Pure PVA was used as a control. The solution of PVA/GA/ε-PL was coated on the UC by plasma-induced surface treatment to ensure optimal coating adhesion. The chemical analysis of the polymer-modified UC was performed by Fourier-Transform Infrared Spectroscopy (FTIR). The antimicrobial activity of modified UC was tested by a disc diffusion method and a colony forming unit/ml method against S. aureus. Results: The disc diffusion method confirmed the antimicrobial activity of polymer-coated UCs through a zones on the plates. The colony-forming unit/ml showed that polymer-coated UCs caused a 4-log reduction compared to the control. The four tested polymer-coated UCs restricted bacterial growth until three dilutions. Confocal microscopy was performed for further confirmation of the antimicrobial properties of the polymer-modified UCs. Sample 1 caused the death of 74% of cells, followed by sample 4 (69%), sample 2 (49%), and sample 3 (43%), whereas in control samples, only 29% of dead bacterial cells were found. Conclusion: Polymer-coated UCs showed promising antimicrobial effects against S. aureus.

Keywords: PVA; PLL; catheter; antimicrobial coatings,;Staphylococcus aureus.

Objective: The repair of large-size skin and bone defects remains an important clinical challenge. On one hand, the microenvironment of trauma is complicated and affects the tissue regeneration. On the other hand, using exogenous growth factors is limited by poor stability, high cost, and dysfunction in a harmful microenvironment. Recently, a great deal of attention has been paid to the development of metal–organic frameworks (MOF) as alternative biomaterials. However, creating MOF with negligible cytotoxicity, excellent chemical stability, ROS scavenging ability, and functions regulating endogenous growth factor production remains challenging.

Results: We synthetized magnesium-seamed and zinc-seamed C-propylpyrogallol[4]arene (PgC₃Mg and PgC₃Zn, separately). These two kinds of metal–organic cages both exhibited excellent stability, biocompatibility, and efficient antioxidant properties. Afterward, we investigated the function of PgC₃Mg in bone regeneration and PgC₃Zn in wound healing. PgC₃Mg promoted osteogenic differentiation of bone-marrow-derived mesenchymal stem cells. In vivo results indicated that PgC₃Mg significantly accelerated cranial bone regeneration. PgC₃Mg functionalized GelMA hydrogel exhibited a better effect than commercial Bio-Gide membranes. Immunostaining showed that PgC₃Mg increased the formation of type H vessels and the expression of platelet-derived growth factor BB. For soft tissue repair, PgC₃Zn exerted a bacteriostatic effect against S. aureus and E. coli, and more significantly promoted proliferation and migration of L929 fibroblast cells compared with ZnCl₂. Animal experiments suggested that PgC₃Zn accelerated acute and that S. aureus infected skin defect healing. Histological staining revealed a high level of collagen deposition, epithelialization, and vascularization after PgC₃Zn treatment. Immunostaining revealed that PgC₃Zn remarkably increased the expression of TGF-β, EGF and VEGF growth factors.

Conclusion: All these results demonstrated that PgC₃Mg and PgC₃Zn are promising treatment strategies in tissue engineering, and have become potential alternative materials for multiple growth factors.

Materials for tissue bioengineering must have a set of properties, such as biocompatibility when interacting with cells in vitro and in vivo, adhesion, proliferation and differentiation of cells in the material. One of the most important requirements for this kind of materials is satisfactory physical and mechanical characteristics that are not inferior to the actual regenerated tissue in a given area of the body. The strength of collagen and chitosan-based materials meet all the requirements when used as matrices for tissue engineering. Block copolymers based on fish collagen and chitosan were obtained 0via ultrasonic irradiation of a mixture of homopolymers. Under the influence of ultrasonic irradiation, two effects— mechanochemical and radical—contribute to the breaking of chains (degradation of macromolecules). As a result, macroradicals are formed that randomly combine with each other. If there are two homopolymers in a solution, then under the influence of ultrasound the chains of both polymers are broken, the resulting macroradicals of different natures recombine and a block copolymer is formed. Films based on the obtained block copolymers of chitosan and collagen are characterized by a tensile strength of up to 120 MPa and are biocompatible with hTert-BJ5ta fibroblast cells. The properties of the material can be controlled by changing the ratio of components, the time of ultrasonic treatment, the molecular weight characteristics of the original homopolymers and the introduction of plasticizers that have a positive effect on the properties of the matrix. The totality of the results obtained shows that compositions based on block copolymers are superior to films made from homopolymers and their mechanical mixtures in terms of mechanical properties, adhesion and proliferation of fibroblast cells. This work was supported by grant of the Russian Science Foundation (project No. 23-13-00342, https://rscf.ru/project/23-13-00342/)

The most common root canal sealers are bioceramic, which release hydroxyl anions and demonstrate bactericidal activity against microorganisms. However, because of its high solubility, this has an impact on sealing capacity as well. Another option is a resin-based sealer, which has a high sealing capacity but is inert to microorganisms. Thus, in this work, an experimental sealer was developed with both features: low solubility and bioactivity due to the use of a polymeric system, and release of the drug N-acetylcysteine (NAC) absorbed onto hydroxyapatite (HAp) nanoparticles incorporated in an epoxy polymer system. Thiol bond interactions allow NAC molecules to disrupt bacterial membranes. Because HAp is soluble in acidic pH, it is expected to release NAC molecules when exposed to a low pH environment.

The sealers were produced by incorporating the particles of interest with a radiopacifier in a mix of resin monomers to form epoxy sealers by chemical polymerization. Physical-chemical properties were determined and compared with a commercial sealer (AH Plus).

As expected, AH Plus demonstrated low sorption in the immersion media and a constant pH. After 28 days, only the Epoxy/NAC and Epoxy/HApNAC groups lost weight in water and PBS, indicating that NAC had been released. However, Epoxy/HApNAC showed lower pH variation across all media, which could be attributed to Epoxy/NAC's lower drug content or particle dimensions. The weight loss in water of Epoxy/NAC (30.23 ± 5.12% w/w) and Epoxy/HApNAC (1.67 ± 0.16%) corroborates with the NAC release profile. Epoxy/HApNAC samples released 49 μmol/L (0,09% mm) of NAC into water. DC data show that the interaction of NAC molecules with epoxy resin polymer chains improves particle compatibility in comparison the Epoxy/HAp group.

The Epoxy/HApNAC group showed similar behavior to the AH Plus group and potential bioactive property by NAC-released content, without compromising the degree of conversion.

The relevance of this study is related to the demand for biocompatible and thermoplastic polymer materials suitable for use in personalized regenerative medicine. Materials based on polycaprolactone and chitosan are recognized as promising candidates for the development of biodegradable materials that successfully combine the properties of synthetic and natural components. The basic idea is that polycaprolactone is convenient from a processing properties perspective, since materials based on it are thermoplastic and have good mechanical properties, but high hydrophobicity and low cellular adhesion limit the use for solving certain medical problems. This can be solved by combining it with chitosan in one composition.

The copolymerization was performed in solution using ultrasonic irradiation. To obtain homogenous solution of chitosan with polycaprolactone, they were dissolved in DMSO and chloroform, respectively, after which both solutions were mixed and irradiated by ultrasonic treatment for 30 minutes at 25 ° C. The structure and properties of the synthesized block copolymers were studied by XRD analysis, gel-permeation chromatography (GPC) and differential scanning calorimetry (DSC). The study of samples by XRD analysis showed the amorphous structure of copolymers, in contrast to the original crystalline homopolymers. The results of DSC study showed a decrease in the melting point of polyester blocks and a decrease in the glass transition temperature of chitosan blocks in the copolymer. The fermentative depolymerization of chitosan blocks in the samples was performed, which made it possible to determine the molecular weight characteristics of the polycaprolactone blocks by GPC study. Films were obtained from block copolymer solutions by the solvent casting method, drying them at 65 ° C to a constant mass. The film samples were characterized by high mechanical properties (tensile strength ~ 70 MPa, with elongation at break ~ 35%). The biocompatibility of the composition was investigated and proven by the MTT assay.

This research was funded by the Russian Science Foundation, grant number 23-13-00342

Three-dimensional (3D) bioprinting has been proven to be the chosen method of fabricating tissue implants and organ models because it can replicate the desired intricate geometries with great accuracy and precision. However, it faces unique challenges distinct from other 3D printing methods, particularly concerning the viscosity of bioink and the multidimensionality of biological structures. There are three fundamental challenges to bioprint any functional tissue, namely 1) achieving shape fidelity for structures in the biological dimensional range with native mechanical properties, 2) ensuring dense vascularization, and 3) attaining cell density akin to native tissue. Despite exploring diverse combinations of bioink materials, achieving consistent success and reproducibility remains challenging. We focused on attaining shape fidelity; here, we have described a 3D printing methodology where chitosan was dissolved in an alkaline solvent, enabling crosslinking with water. Rheological assessment of the bioink using the Power law model illustrated its shear-thinning properties, which is essential for extrusion-based 3D bioprinting. Printing parameters were optimized. The 3D bioprinting was carried out within a support hydrogel comprising thermoresponsive gelatin showing Bingham rheology. This supportive material prevented the collapse of the printed structures. Post-printing, the structures were crosslinked by pouring 40ºC water into the print container, simultaneously melting the support medium, and facilitating the recovery of the 3D bioprinted complex structure like a tri-leaflet heart valve, etc. The printed dimensional accuracy was in the range of .stl file dimensions. The mechanical properties of the printed structures fall in the range of native human soft tissue, i.e. 0.1KPa–1MPa. The degradation study described the variation in stability of the 3D bioprinted construct at different incubation conditions. Utilizing chitosan-based bioink and support-driven 3D bioprinting presents a promising avenue for creating intricate vascular structures, propelling advancements in tissue engineering and diverse biomedical applications.

Currently, mediator biosensors make it possible to determine the glucose content in biological fluids, food products and other complex samples, and the urgent task today is to develop the most convenient and accurate online biosensor for determining glucose levels. The developed biosensor includes a portable potentiostat, a 5 ml measuring cell and a screen-printed electrode. The working surface of the screen-printed electrode is modified with single-walled carbon nanotubes, bovine serum albumin covalently bound wuth neutral red and a glucose oxidase enzyme. Modification of bovine serum albumin with neutral red was carried out using glutaraldehyde. All measurements were carried out at pH = 7.0 (phosphate buffer solution, buffer solution salt concentration of 33 mM) and at an applied potential of -0.7 V. Modification of the working electrode with a biocomposite makes it possible to analyze glucose in the range of 0.1 – 60 mM. The functioning time of the system is 29 days. This range allows us to carry out online glucose monitoring of human blood samples, as well as of tear fluid, where glucose levels should average 0.1-0.3 mM for non-invasive measurements. The biosensor was tested on three samples of physiological fluids; a comparison of the results obtained with the data from the standard method using the Student's statistical test and Welch approximation showed a statistically insignificant difference in the results obtained via the different methods of analysis. Thus, the developed system may become an alternative analytical system for non-invasive monitoring of glucose levels in the future.

The study was supported by the Russian Science Foundation, grant No. 23-73-01220, https://rscf.ru/project/23-73-01220/»