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This study investigates the biodistribution of polysaccharide-based nanoparticles loaded with epirubicin (POLEPI) compared to epirubicin hydrochloride (EPI) in naïve female nude mice following a single intravenous dose. The inherent fluorescence of epirubicin was tracked using Newton 7 animal imager and Varioskan. Initial whole-animal optical imaging failed to reliably detect epirubicin distribution, necessitating ex vivo imaging of key tissues harvested at intervals between 10 min and 48 h post-injection. Optimal imaging conditions were established using a 5 s exposure time with excitation (Ex)/emission (Em) at 480 nm/550 nm. The biodistribution of POLEPI was further evaluated in both naïve mice and immunocompromised mice bearing patient-derived ovarian tumors. Unlike epirubicin, POLEPI exhibited notable tissue distribution within 3 h post-injection. By 48 h, fluorescence signals were undetectable in both models, although non-tumored animals exhibited persistent signals. In both models, the liver was the primary organ for POLEPI accumulation, with lower levels in tumored mice. Interestingly, brain fluorescence was higher in POLEPI-treated mice compared to those receiving epirubicin. Neither POLEPI nor epirubicin accumulated in the spleen or bone marrow. In tumors, POLEPI fluorescence peaked at 24 h, with levels 2.1 times higher than in the epirubicin-treated group over a 48 h period. Furthermore, POLEPI uptake in tumors exceeded that in healthy ovaries, with the most significant tumor-to-healthy-ovary ratio observed between 6 and 24 h post-injection. These findings demonstrate that POLEPI, a novel polyaldehydedextran nanoparticle formulation, exhibits enhanced accumulation and retention in tumor tissue compared to epirubicin, with preferential distribution to the orthotopic tumor-bearing ovary over healthy ovarian tissue. The inherent fluorescence of epirubicin provided a rapid and cost-effective means of estimating biodistribution, although the limitations of this method-particularly, the inability to differentiate between the parent drug and its metabolites-were acknowledged.

One of the promising candidates for new antimicrobial agents is membrane-lytic compounds that kill microbes through cell membrane permeabilization, such as antimicrobial peptides (AMPs) and their synthetic mimics (SMAMPs). Although SMAMPs have been under investigation for nearly 30 years, a few challenges must be addressed before they can reach clinical use. In this work, a step-growth polymerization leading to already-known highly antimicrobial ionenes was redirected toward the formation of macrocyclic quaternary ammonium salts (MQAs) employing a high dilution principle. Antimicrobial assays and cytotoxicity studies revealed the high antimicrobial activity of MQAs and better selectivity than their polymeric analogues. Therefore, MQAs seem to be a new class of promising antibacterial agents. Additionally, membrane-lytic experiments using large unilamellar liposomes (LUVs) and whole cells revealed significant differences between MQAs and ionenes in their ability to adsorb onto the surface of LUVs and microbes as well as their ability to permeate the lipid bilayer.

Introduction: Several complications of retrograde intrarenal surgery have been attributed to inadvertent increases in intrarenal pressure. We recently described the development of an innovative isoprenaline-eluting guidewire (IsoWire). The objective of this study was to investigate the impact of this IsoWire on the intrarenal pressure and evaluate its safety. Materials and Methods: This study was performed in 17 renal units using a porcine model. As controls, the intrarenal pressure, heart rate, and mean arterial pressure were measured for a duration of six minutes with a standard guidewire placed in the renal pelvis. For the experiment, the conventional guidewire was substituted with the IsoWire and the same parameters were measured. Blood samples were taken at one-minute intervals to measure plasma isoprenaline levels. This procedure was repeated on the opposite side. Results: The mean intrarenal pressure reduction was 29% (95% CI: 13%-53%). The mean isoprenaline effect time was 174 seconds. No changes in heart rate ( p = .908) or mean arterial pressure ( p = .749) were recorded after IsoWire insertion. Plasma isoprenaline levels were below the quantitation threshold. Isoprenaline concentrations in the plasma were below the quantification threshold. Ureteroscopy revealed no ureteral lesions. Conclusions: The IsoWire demonstrated a safe and effective reduction of intrarenal pressure. Additional research is necessary to determine whether ureteral smooth muscle relaxation generated by isoprenaline facilitates easier insertion of a ureteral access sheath, decreases the incidence of ureteral access sheath related ureteral lesions, or even encourage the practice of sheathless retrograde intrarenal surgery.

In this study, fibrous polyurethane (PU) materials with average fiber diameter of 200, 500, and 1000 nm were produced using a solution blow spinning (SBS) process. The effects of the rotation speed of the collector (in the range of 200-25 000 rpm) on the fiber alignment and diameter were investigated. The results showed that fiber alignment was influenced by the rotation speed of the collector, and such alignment was possible when the fiber diameter was within a specific range. Homogeneously oriented fibers were obtained only for a fiber diameter ≥500 nm. Moreover, the changes in fiber orientation and fiber diameter (resulting from changes in the rotation speed of the collector) were more noticeable for materials with an average fiber diameter of 1000 nm in comparison to 500 nm, which suggests that the larger the fiber diameter, the better the controlled architectures that can be obtained. The porosity of the produced scaffolds was about 65-70%, except for materials with a fiber diameter of 1000 nm and aligned fibers, which had a higher porosity (76%). Thus, the scaffold pore size increased with increasing fiber diameter but decreased with increasing fiber alignment. The mechanical properties of fibrous materials strongly depend on the direction of stretching, whereby the fiber orientation influences the mechanical strength only for materials with a fiber diameter of 1000 nm. Furthermore, the fiber diameter and alignment affected the pericyte growth. Significant differences in cell growth were observed after 7 days of cell culture between materials with a fiber diameter of 1000 nm (cell coverage 96-99%) and those with a fiber diameter of 500 nm (cell coverage 70-90%). By appropriately setting the SBS process parameters, scaffolds can be easily adapted to the cell requirements, which is of great importance in producing complex 3D structures for guided tissue regeneration.

3D printing is a promising technique for producing bone implants, but there is still a need to adjust efficiency, facilitate production, and improve biocompatibility. Porous materials have a proven positive effect on the regeneration of bone tissue, but their production is associated with numerous limitations. In this work, we described a simple method of producing polymer or polymer-ceramic filaments for 3D-printing scaffolds by adding micrometer-scale porous structures on scaffold surfaces. Scaffolds included polycaprolactone (PCL) as the primary polymer, β-tricalcium phosphate (β-TCP) as the ceramic filler, and poly(ethylene glycol) (PEG) as a porogen. The pressurized filament extrusion gave flexible filaments composed of PCL, β-TCP, and PEG, which are ready to use in fused filament fabrication (FFF) 3D printers. Washing of 3D-printed scaffolds in ethanol solution removed PEG and revealed a microporous structure and ceramic particles on the scaffold's surfaces. Furthermore, 3D-printed materials exhibit good printing precision, no cytotoxic properties, and highly impact MG63 cell alignment. Although combining PCL, PEG, and β-TCP is quite popular, the presented method allows the production of porous scaffolds with a well-organized structure without advanced equipment, and the produced filaments can be used to 3D print scaffolds on a simple commercially available 3D printer., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Introduction: Retrograde intrarenal surgery (RIRS) is associated with complications, many of which are related to the intrarenal pressure (IRP). We aim to describe the design of a novel isoprenaline-eluting guidewire ("IsoWire") and present the results from the first in vitro release studies and the first animal studies showing its effect on IRP. Materials and Methods: The IsoWire comprises a Nitinol core surrounded by a stainless-steel wire wound into a tight coil. The grooves created by this coil provided a reservoir for adding a hydrogel coating into which isoprenaline, a beta-agonist, was loaded. Animal studies were performed using a porcine model. For the control, IRP, heart rate (HR), and mean arterial pressure (MAP) were measured continuously for 6 minutes with a standard guidewire in place. For the experiment, the standard hydrophilic guidewire was removed, the IsoWire was inserted into the renal pelvis, and the same parameters were measured. Results: In vitro analysis of the isoprenaline release profile showed that most (63.9 ± 5.9%) of the loaded drug mass was released in the 1st minute, and almost all of the drug was released in the first 4 minutes exponentially. Porcine studies showed a 25.1% reduction in IRP in the IsoWire that released 10 μg in the 1st minute; however, there was a marked increase in HR. The average percentage reduction in IRP was 8.95% and 21.3% in the IsoWire that released 5 and 7.5 μg of isoprenaline, respectively, with no changes in HR or MAP. Conclusions: The IsoWire, which releases 5 and 7.5 μg of isoprenaline in the 1st minute, appears to be safe and effective in reducing the IRP. Further studies are needed to establish whether the isoprenaline-induced ureteral relaxation will render easier insertion of a ureteral access sheath, reduce IRP during sheathless RIRS, or even promote the practice of sheathless RIRS.

The challenge of integrating hydroxyapatite nanoparticles (nHAp) with polymers is hindered by the conflict between the hydrophilic and hygroscopic properties of nHAp and the hydrophobic properties of polymers. This conflict particularly affects the materials when calcium phosphates, including nHAp, are used as a filler in composites in thermal processing applications such as 3D printing with fused filament fabrication (FFF). To overcome this, we propose a one-step surface modification of nHAp with calcium stearate monolayer. Moreover, to build the scaffold with suitable mechanical strength, we tested the addition of nHAp with diverse morphology-spherical, plate- and rod-like nanoparticles. Our analysis showed that the composite of polycaprolactone (PCL) reinforced with nHAp with rod and plate morphologies modified with calcium stearate monolayer exhibited a significant increase in compressive strength. However, composites with spherical nHAp added to PCL showed a significant reduction in compressive modulus and compressive strength, but both parameters were within the applicability range of hard tissue scaffolds. None of the tested composite scaffolds showed cytotoxicity in L929 murine fibroblasts or MG-63 human osteoblast-like cells, supporting the proliferation of the latter. Additionally, PCL/nHAp scaffolds reinforced with spherical nHAp caused osteoactivation of bone marrow human mesenchymal stem cells, as indicated by alkaline phosphatase activity and COL1, RUNX2, and BGLAP expression. These results suggest that the calcium stearate monolayer on the surface of the nHAp particles allows the production of polymer/nHAp composites suitable for hard tissue engineering and personalized implant production in 3D printing using the FFF technique., (© 2024 Wiley Periodicals LLC.)

Epirubicin hydrochloride (EPI) is an anticancer drug widely used in the treatment of many solid tumors, including ovarian cancer. Because of its anatomical location, ovarian cancer shows symptoms when it is already in an advanced stage and is thus more difficult to treat. Epirubicin hydrochloride kills cancer cells effectively, but its dose escalation is limited by its severe toxicity. By encapsulating epirubicin in dextran-based nanoparticles (POLEPI), we expected to deliver higher and thus clinically more effective doses directly to tumors, where epirubicin would be released and retained longer in the tumor. The antitumor activity of POLEPI compared to EPI was first tested ex vivo in a series of ovarian cancer patient-derived tumor xenografts (PDX). The most promising PDX was then implanted orthotopically into immunocompromised mice, and tumor growth was monitored via magnetic resonance imaging (MRI). Although we succeeded in suppressing the growth of ovarian cancer derived from a patient, in a mouse model by 70% compared to 40% via EPI in 5 days after only one injection, we could not eliminate serious side effects, and the study was terminated prematurely for humane reasons.

New prophylactic vaccine platforms are imperative to combat respiratory infections. The efficacy of T and B memory cell-mediated protection, generated through the adenoviral vector, was tested to assess the effectiveness of the new adenoviral-based platforms for infectious diseases. A combination of adenovirus AdV1 (adjuvant), armed with costimulatory ligands (ICOSL and CD40L), and rRBD (antigen: recombinant nonglycosylated spike protein rRBD) was used to promote the differentiation of T and B lymphocytes. Adenovirus AdV2 (adjuvant), without ligands, in combination with rRBD, served as a control. In vitro T-cell responses to the AdV1+rRBD combination revealed that CD8+ platform-specific T-cells increased (37.2 ± 0.7% vs. 23.1 ± 2.1%), and T-cells acted against SARS-CoV-2 via CD8+TEMRA (50.0 ± 1.3% vs. 36.0 ± 3.2%). Memory B cells were induced after treatment with either AdV1+rRBD (84.1 ± 0.8% vs. 82.3 ± 0.4%) or rRBD (94.6 ± 0.3% vs. 82.3 ± 0.4%). Class-switching from IgM and IgD to isotype IgG following induction with rRBD+Ab was observed. RNA-seq profiling identified gene expression patterns related to T helper cell differentiation that protect against pathogens. The analysis determined signaling pathways controlling the induction of protective immunity, including the MAPK cascade, adipocytokine, cAMP, TNF, and Toll-like receptor signaling pathway. The AdV1+rRBD formulation induced IL-6, IL-8, and TNF. RNA-seq of the VERO E6 cell line showed differences in the apoptosis gene expression stimulated with the platforms vs. mock. In conclusion, AdV1+rRBD effectively generates T and B memory cell-mediated protection, presenting promising results in producing CD8+ platform-specific T cells and isotype-switched IgG memory B cells. The platform induces protective immunity by controlling the Th1, Th2, and Th17 cell differentiation gene expression patterns. Further studies are required to confirm its effectiveness., Competing Interests: The authors declare that they have no competing interests., (© 2023 Institute of Bioorganic Chemistry, Polish Academy of Sciences.)

The nanoprecipitation method was used to formulate ε-polycaprolactone (PCL) into fluorescent nanoparticles. Two methods of mixing the phases were evaluated: introducing the organic phase into the aqueous phase dropwise and via a specially designed microfluidic device. As a result of the nanoprecipitation process, fluorescein-loaded nanoparticles (NPs) with a mean diameter of 127 ± 3 nm and polydispersity index (PDI) of 0.180 ± 0.009 were obtained. The profiles of dye release were determined in vitro using dialysis membrane tubing, and the results showed a controlled release of the dye from NPs. In addition, the cytotoxicity of the NPs was assessed using an MTT assay. The PCL NPs were shown to be safe and non-toxic to L929 and MG63 cells. The results of the present study have revealed that PCL NPs represent a promising system for developing new drug delivery systems.

The aim of this study was to investigate the process of attachment of saccharide particles differing in degree of complexity to cell receptors responsible for transport of glucose across the cell membrane (GLUT proteins). This phenomenon is currently considered when designing modern medicines, e.g., peptide drugs to which glucose residues are attached, enabling drugs to cross the barrier of cell membranes and act inside cells. This study aims to help us understand the process of assimilation of polysaccharide nanoparticles by tumour cells. In this study, the interactions between simple saccharides (glucose and sucrose) and dextran nanoparticles with two species of GLUT proteins (GLUT1 and GLUT4) were measured using the surface plasmon resonance technique. We managed to observe the interactions of glucose and sucrose with both applied proteins. The lowest concentration that resulted in the detection of interaction was 4 mM of glucose on GLUT1. Nanoparticles were measured using the same proteins with a detection limit of 40 mM. These results indicate that polysaccharide nanoparticles interact with GLUT proteins. The measured strengths of interactions differ between proteins; thus, this study can suggest which protein is preferable when considering it as a mean of nanoparticle carrier transport.

3D printing technology can deliver tailored, bioactive, and biodegradable bone implants. However, producing the new, experimental material for a 3D printer could be the first and one of the most challenging steps of the whole bone implant 3D printing process. Production of polymeric and polymer-ceramic filaments involves using costly filament extruders and significantly consuming expensive medical-grade materials. Commercial extruders frequently require a large amount of raw material for experimental purposes, even for small quantities of filament. In our publication, we propose a simple system for pressure filament extruding, which allows obtaining up to 1-meter-long filament suitable for fused filament fabrication-type 3D printers, requiring only 30 g of material to begin work. Our device is based on stainless steel pipes used as a container for material, a basic electric heating system with a proportional-integral-derivative controller, and a pressurised air source with an air pressure regulator. We tested our device on various mixes of polylactide and polycaprolactone with β-tricalcium phosphate and demonstrated the possibility of screening production and testing of new materials for 3D-printed bone implants., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

In this article, we have demonstrated the feasibility of generating an active form of recombinant blood coagulation factor VIII using an E. coli bacterial expression system as a potential treatment for hemophilia type A. Factor VIII (FVIII), an essential blood coagulation protein, is a key component of the fluid phase blood coagulation system. So far, all available recombinant FVIII formulations have been produced using eukaryotic expression systems. Mammalian cells can produce catalytically active proteins with all the necessary posttranslational modifications. However, cultivating such cells is time-consuming and highly expensive, and the amount of the obtained product is usually low. In contrast to eukaryotic cells, bacterial culture is inexpensive and allows the acquisition of large quantities of recombinant proteins in a short time. With this study, we aimed to obtain recombinant blood coagulation factor VIII using the E. coli bacterial expression system, a method not previously explored for this purpose. Our research encompasses the synthesis of blood coagulation factor VIII and its expression in a prokaryotic system. To achieve this, we constructed a prokaryotic expression vector containing a synthetic factor VIII gene, which was then used for the transformation of an E. coli bacterial strain. The protein expression was confirmed by mass spectrometry, and we assessed the stability of the gene construct while determining the optimal growth conditions. The production of blood coagulation factor VIII by the E. coli bacterial strain was carried out on a quarter-technical scale. We established the conditions for isolation, denaturation, and renaturation of the protein, and subsequently confirmed the activity of FVIII., Competing Interests: The authors declare that they have no competing interests., (© 2023 Institute of Bioorganic Chemistry, Polish Academy of Sciences.)

Polyester-based granular scaffolds are a potent material for tissue engineering due to their porosity, controllable pore size, and potential to be molded into various shapes. Additionally, they can be produced as composite materials, e.g., mixed with osteoconductive β-tricalcium phosphate or hydroxyapatite. Such polymer-based composite materials often happen to be hydrophobic, which disrupts cell attachment and decreases cell growth on the scaffold, undermining its primary function. In this work, we propose the experimental comparison of three modification techniques for granular scaffolds to increase their hydrophilicity and cell attachment. Those techniques include atmospheric plasma treatment, polydopamine coating, and polynorepinephrine coating. Composite polymer/β-tricalcium phosphate granules have been produced in a solution-induced phase separation (SIPS) process using commercially available biomedical polymers: poly(lactic acid), poly(lactic-co-glycolic acid), and polycaprolactone. We used thermal assembly to prepare cylindrical scaffolds from composite microgranules. Atmospheric plasma treatment, polydopamine coating, and polynorepinephrine coating showed similar effects on polymer composites' hydrophilic and bioactive properties. All modifications significantly increased human osteosarcoma MG-63 cell adhesion and proliferation in vitro compared to cells cultured on unmodified materials. In the case of polycaprolactone/β-tricalcium phosphate scaffolds, modifications were the most necessary, as unmodified polycaprolactone-based material disrupted the cell attachment. Modified polylactide/β-tricalcium phosphate scaffold supported excellent cell growth and showed ultimate compressive strength exceeding this of human trabecular bone. This suggests that all investigated modification techniques can be used interchangeably for increasing wettability and cell attachment properties of various scaffolds for medical applications, especially those with high surface and volumetric porosity, like granular scaffolds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Biomaterial's surface functionalization for selective adhesion and patterned cell growth remains essential in developing novel implantable medical devices for regenerative medicine applications. We built and applied a 3D-printed microfluidic device to fabricate polydopamine (PDA) patterns on the surface of polytetrafluoroethylene (PTFE), poly(l-lactic acid- co -D,l-lactic acid) (PLA), and poly(lactic acid- co -glycolic acid) (PLGA). Then, we covalently attached the Val-Ala-Pro-Gly (VAPG) peptide to the created PDA pattern to promote the adhesion of the smooth muscle cells (SMCs). We proved that the fabrication of PDA patterns allows for the selective adhesion of mouse fibroblast and human SMCs to PDA-patterned surfaces after only 30 min of in vitro cultivation. After 7 days of SMC culture, we observed the proliferation of cells only along the patterns on PTFE but over the entire surface of the PLA and PLGA, regardless of patterning. This means that the presented approach is beneficial for application to materials resistant to cell adhesion and proliferation. The additional attachment of the VAPG peptide to the PDA patterns did not bring measurable benefits due to the high increase in adhesion and patterned cell proliferation by PDA itself., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Antimicrobial peptides (AMPs), or host defence peptides, are short proteins in various life forms. Here we discuss AMPs, which may become a promising substitute or adjuvant in pharmaceutical, biomedical, and cosmeceutical uses. Their pharmacological potential has been investigated intensively, especially as antibacterial and antifungal drugs and as promising antiviral and anticancer agents. AMPs exhibit many properties, and some of these have attracted the attention of the cosmetic industry. AMPs are being developed as novel antibiotics to combat multidrug-resistant pathogens and as potential treatments for various diseases, including cancer, inflammatory disorders, and viral infections. In biomedicine, AMPs are being developed as wound-healing agents because they promote cell growth and tissue repair. The immunomodulatory effects of AMPs could be helpful in the treatment of autoimmune diseases. In the cosmeceutical industry, AMPs are being investigated as potential ingredients in skincare products due to their antioxidant properties (anti-ageing effects) and antibacterial activity, which allows the killing of bacteria that contribute to acne and other skin conditions. The promising benefits of AMPs make them a thrilling area of research, and studies are underway to overcome obstacles and fully harness their therapeutic potential. This review presents the structure, mechanisms of action, possible applications, production methods, and market for AMPs.

Cationic polymers have been extensively investigated as a potential replacement for traditional antibiotics. Here, we examined the effect of molecular weight (MW) on the antimicrobial, cytotoxic, and hemolytic activity of linear polytrimethylenimine (L-PTMI). The results indicate that the biological activity of the polymer sharply increases as MW increases. Thanks to a different position of the antibacterial activity and toxicity thresholds, tuning the MW of PTMI allows one to achieve a therapeutic window between antimicrobial activity and toxicity concentrations. L-PTMI presents significantly higher antimicrobial activity against model microorganisms than linear polyethylenimine (L-PEI) when polymers with a similar number of repeating units are compared. For the derivatives of L-PTMI and L-PEI, obtained through N -monomethylation and partial N,N -dimethylation of linear polyamines, the antimicrobial activity and toxicity were both reduced; however, resulting selectivity indices were higher. Selected materials were tested against clinical isolates of pathogens from the ESKAPE group and Mycobacteria , revealing good antibacterial properties of L-PTMI against antibiotic-resistant strains of Gram-positive and Gram-negative bacteria but limited antibacterial properties against Mycobacteria .

Polysaccharides are the most abundant polymers in nature. They exhibit robust biocompatibility, reliable non-toxicity, and biodegradable character; thus, they are employed in multiple biomedical applications. The presence of chemically accessible functional groups on the backbone of biopolymers (amine, carboxyl, hydroxyl, etc.) makes them suitable materials for chemical modification or drug immobilisation. Among different drug delivery systems (DDSs), nanoparticles have been of great interest in scientific research in the last decades. In the following review, we want to address the issue of rational design of nanoparticle (NP)-based drug delivery systems in reference to the specificity of the medication administration route and resulting requirements. In the following sections, readers can find a comprehensive analysis of the articles published by authors with Polish affiliations in the last few years (2016-2023). The article emphasises NP administration routes and synthetic approaches, followed by in vitro and in vivo attempts toward pharmacokinetic (PK) studies. The 'Future Prospects' section was constructed to address the critical observations and gaps found in the screened studies, as well as to indicate good practices for polysaccharide-based nanoparticle preclinical evaluation.

Background: In this study, two types of polyurethane-based cylindrical multilayered grafts with internal diameters ≤ 6 mm were produced by the solution blow spinning (SBS) method. The main aim was to create layered-wall prostheses differing in their luminal surface morphology. Changing the SBS process parameters, i.e. working distance, rotational speed, volume, and concentration of the polymer solution allowed to obtain structures with the required morphologies. The first type of prostheses, termed Nano, possessed nanofibrous luminal surface, and the second type, Micro, presented morphologically diverse luminal surface, with both solid and microfibrous areas., Results: The results of mechanical tests confirmed that designed prostheses had high flexibility (Young's modulus value of about 2.5 MPa) and good tensile strength (maximum axial load value of about 60 N), which meet the requirements for vascular prostheses. The influence of the luminal surface morphology on platelet adhesion and the attachment of endothelial cells was investigated. Both surfaces did not cause hemolysis in contact with blood, the percentage of platelet-occupied area for Nano and Micro surfaces was comparable to reference polytetrafluoroethylene (PTFE) surface. However, the change in morphology of surface-adhered platelets between Nano and Micro surfaces was visible, which might suggest differences in their activation level. Endothelial coverage after 1, 3, and 7 days of culture on flat samples (2D model) was higher on Nano prostheses as compared with Micro scaffolds. However, this effect was not seen in 3D culture, where cylindrical prostheses were colonized using magnetic seeding method., Conclusions: We conclude the produced scaffolds meet the material and mechanical requirements for vascular prostheses. However, changing the morphology without changing the chemical modification of the luminal surface is not sufficient to achieve the appropriate effectiveness of endothelialization in the 3D model., (© 2023. The Author(s).)

3D printing is a promising technique for obtaining bone implants. However, 3D printed bone implants, especially those printed using fused deposition modelling, are still in the experimental phase despite decades of work. Research on new materials faces numerous limitations, such as reagents' cost and machines' high prices to produce filaments for 3D printing polymer-ceramic composites for fused deposition modelling. This paper presents a simple, low-cost, and fast method of obtaining polymer-ceramic filaments using apparatus consisting of parts available in a hardware store. The method's versatility for producing the filaments was demonstrated on two different biodegradable polymers - polylactic acid and polycaprolactone - and different concentrations of calcium phosphate - β-tricalcium phosphate - in the composite, up to 50 % by weight. For screening purposes, numerous scaffolds were 3D printed from the obtained filaments on a commercial 3D printer. Structural, mechanical, and biological tests show that the 3D printed scaffolds are suitable for bone implants, as their structure, mechanical, and non-cytotoxic properties are evident. Moreover, the proposed method of composite forming is a simplification of the processes of manufacturing and researching 3D printed materials with potential applications in the regeneration of bone tissue., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The ocular delivery route presents a number of challenges in terms of drug administration and bioavailability. The low bioavailability following topical ophthalmic administration shows that there is a clear need for in-depth research aimed at finding both more efficacious molecules and formulations precisely targeted at the site of action. Continuous technological development will eventually result in improved bioavailability, lower dosages, reduced toxicity, fewer adverse effects, and thus better patient compliance and treatment efficacy. Technological development, as well as increasingly stringent quality requirements, help stimulate analytical progress. This is also clearly evident in the case of medicinal products used in the treatment of glaucoma, which are the subject of this review. Impurity profiling of PGF2α analogues, either in the pure substance or in the finished formulation, is a crucial step in assessing their quality. The development of specific, accurate and precise stability-indicating analytical methods for determining the content and related substances seems to be an important issue in relation to this tasks. A total of 27 official and in-house analytical methods are presented that are used for the analysis of latanoprost, travoprost and bimatoprost. The conditions for chromatographic separation with UV or MS/MS detection and the available results obtained during method validation are described. In addition, several aspects are discussed, with particular emphasis on the instability of the analogues in aqueous solution and the phenomenon of isomerism, which affects a potentially large number of degradation products., (Copyright © 2022. Published by Elsevier B.V.)

Synthetic bone repair materials are becoming increasingly popular in tissue engineering as a replacement for autografts and human/animal-based bone grafts. The biomedical application requires precise control over the material composition and structure, as well as over the size of granulate used for filling the bone defects, as the pore size and interconnectivity affect the regeneration process. This paper proposes a process of alloplastic and biodegradable polylactic acid/β-tricalcium phosphate granulates preparation and its parameters described. Using solvent-induced phase separation technique, porous spheres have been obtained in various sizes and morphologies. The design of the experiment's approach generated an experimental plan for further statistical modeling using the resulting data. The statistical modeling approach to the data from conducting a designed set of experiments allowed analysis of the influence of process parameters on the properties of the resulting granules. We confirmed that the content of β-tricalcium phosphate plays the most significant role in the size distribution of prepared granulate. The shape of the particles becomes less spherical with higher phosphate concentration in the emulsion. The proposed technique allows preparing porous granulates in the 0.2-1.8 mm diameter range, where granules' mean diameter and sphericity are tunable with polymer and phosphate concentrations. The granulate created a potentially implantable scaffold for resected bone regeneration, as cytotoxicity tests assured the material is non-cytotoxic in vitro, and human mesenchymal stem cells have been cultured on the surface of granulates. Results from cell cultures seeded on the Resomer LR 706S granulates were the most promising., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In the present work, a solution blow spun nanofibrous mat comprised of chitosan (CS) and poly(ethylene oxide) (PEO) was obtained as vaginal platform for tenofovir disoproxil fumarate (TDF) to prevent sexually transmitted infections. Apart from physicochemical and mechanical analysis, the specific steps involved studies on nanofibrous mat mucoadhesive and swelling characteristics upon pH fluctuations over the physiological range. Physicochemical analysis showed uniform drug distribution within the CS/PEO mat volume and pointed toward physical interactions between the drug and polymers. TDF-loaded CS/PEO nanofibrous mat was shown potentially safe when evaluated by the MTT metabolic activity and JC-1 assays in human vaginal epithelial cells VK2-E6/E7. In vitro antiviral studies indicated inhibition efficacy of TDF-CS/PEO nanofibrous mat toward HSV-2 virus and proved the SBS process does not change the microbicidal activity of drug molecule. Fluctuations in the physiological vaginal pH range of 3.8 to 5.0 substantially affected mucoadhesive and swelling behavior of chitosan which in turn impacted drug dissolution rate from polymer carrier. The rate of permeation and accumulation of TDF in vaginal tissue differed in response to vaginal pH. Faster drug permeation assessed at pH 5.0 suggests that an increase in vaginal pH could improve TDF bioavailability at earlier time points., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Surface properties are crucial for medical device and implant research and applications. We present novel polycatecholamine coatings obtained by oxidative polymerization of l-tyrosine, l-phenylalanine, and 2-phenylethylamine based on mussel glue-inspired chemistry. We optimized the reaction parameters and examined the properties of coatings compared to the ones obtained from polydopamine. We produced polycatecholamine coatings on various materials used to manufacture implantable medical devices, such as polyurethane, but also hard-to-coat polydimethylsiloxane, polytetrafluoroethylene, and stainless steel. The coating process results in significant hydrophilization of the material's surface, reducing the water contact angle by about 50 to 80% for polytetrafluoroethylene and polyurethane, respectively. We showed that the thickness, roughness, and stability of the polycatecholamine coatings depend on the chemical structure of the oxidized phenylamine. In vitro experiments showed prominent hemocompatibility of our coatings and significant improvement of the adhesion and proliferation of human umbilical vein endothelial cells. The full confluence on the surface of coated polytetrafluoroethylene was achieved after 5 days of cell culture for all tested polycatecholamines, and it was maintained after 14 days. Hence, the use of polycatecholamine coatings can be a simple and versatile method of surface modification of medical devices intended for contact with blood or used in tissue engineering., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

The spread of antibiotic-resistant pathogens and the resurgence of tuberculosis disease are major motivations to search for novel antimicrobial agents. Some promising candidates in this respect are cationic polymers, also known as synthetic mimics of antimicrobial peptides (SMAMPs), which act through the membrane-lytic mechanism. Development of resistance toward SMAMPs is less likely than toward currently employed antibiotics; however, further studies are needed to better understand their structure-activity relationship. The main objective of this work is to understand the cross-influence of hydrophobicity, main-chain flexibility, and the topology of ionenes (polycations containing a cationic moiety within the main-chain) on activity. To fulfill this goal, a library of ionenes was developed and compared with previously investigated molecules. The obtained compounds display promising activity against the model microorganisms and drug-resistance clinical isolates, including Mycobacterium tuberculosis . The killing efficiency was also investigated, and results confirm a strong effect of hydrophobicity, revealing higher activity for molecules possessing the flexible linker within the polymer main-chain., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Iron oxide nanoparticles are commonly used in many medical applications as they can be easily modified, have a high surface-to-volume ratio, and are biocompatible and biodegradable. This study was performed to synthesize nanoparticles designed for multimodal HER2-positive cancer treatment involving radionuclide therapy and magnetic hyperthermia. The magnetic core (Fe 3 O 4 ) was coated with a gold-198 layer creating so-called core-shell nanoparticles. These were then further modified with a bifunctional PEG linker and monoclonal antibody to achieve the targeted therapy. Monoclonal antibody-trastuzumab was used to target specific breast and nipple HER2-positive cancer cells. The nanoparticles measured by transmission electron microscopy were as small as 9 nm. The bioconjugation of trastuzumab was confirmed by two separate methods: thermogravimetric analysis and iodine-131 labeling. Synthesized nanoparticles showed that they are good heat mediators in an alternating magnetic field and exhibit great specific binding and internalization capabilities towards the SKOV-3 (HER2 positive) cancer cell line. Radioactive nanoparticles also exhibit capabilities regarding spheroid degradation without and with the application of magnetic hyperthermia with a greater impact in the case of the latter. Designed radiobioconjugate shows great promise and has great potential for in vivo studies regarding magnetic hyperthermia and radionuclide combined therapy.

An alarming increase of antibiotic resistance among pathogens creates an urgent need to develop new antimicrobial agents. Many reported polycations show high antimicrobial activity along with low hemolytic activity. Unfortunately, most of those molecules remain highly cytotoxic against various mammalian cells. In this work, a systematic study on the impact of triethylene glycol monomethyl ether side groups (short polyethylene glycol (PEG) analog) on antimicrobial, hemolytic, and cytotoxic properties of novel amphiphilic ionenes is presented. A detailed description of synthesis, leading to well-defined alternating polymers, which differ in structural elements responsible for hydrophilicity (PEG) and hydrophobicity (alkyl chain), is presented. Obtained results show that the PEG moiety and fine-tuned hydrophilic-lipophilic balance of ionenes synergistically lead to low cytotoxic, low hemolytic molecules with high activity against S. aureus, including methicillin-resistant strains (MRSA). Additionally, the results of mechanistic studies on bacterial cells and fluorescently labeled liposomes are also discussed., (© 2022 Wiley-VCH GmbH.)

Nanofibrous materials are widely investigated as a replacement for the extracellular matrix, the 3D foundation for cells in all tissues. However, as with every medical material, nanofibers too must pass all safety evaluations like in vitro cytotoxicity assays or in vivo animal tests. Our literature research showed that differences in results of widely used cytotoxicity assays applied to evaluate nanofibrous materials are poorly understood. To better explore this issue, we prepared three nanofibrous materials with similar physical properties made of poly-L-lactic acid, polyurethane, and polycaprolactone. We tested five metabolic cytotoxicity assays (MTT, XTT, CCK-8, alamarBlue, PrestoBlue) and obtained different viability results for the same nanofibrous materials. Further, the study revealed that nanofibrous materials affect the reaction of cytotoxicity assays. Considering the results of both described experiments, it is evident that validating all available cytotoxicity assays for nanofibrous materials and possibly other highly porous materials should be carefully planned and verified using an additional analytical tool, like scanning electron microscopy or, more preferably, confocal microscopy., (© 2022. The Author(s).)

Chitosan (CS)/poly(ethylene oxide) (PEO)-based nanofiber mats have attracted particular attention as advanced materials for medical and pharmaceutical applications. In the scope of present studies, solution blow spinning was applied to produce nanofibers from PEO and CS and physicochemical and biopharmaceutical studies were carried out to investigate their potential as wound nanomaterial for skin healing and regeneration. Additional coating with hydrophobic poly(dimethylsiloxane) was applied to favor removal of nanofibers from the wound surface. Unmodified nanofibers displayed highly porous structure with the presence of uniform, randomly aligned nanofibers, in contrast to coated materials in which almost all the free spaces were filled in with poly(dimethylsiloxane). Infrared spectroscopy indicated that solution blow technique did not influence the molecular nature of native polymers. Obtained nanofibers exhibited sufficient wound exudate absorbency, which appears beneficial to moisturize the wound bed during the healing process. Formulations displayed greater tensile strength as compared to commercial hydrofiber-like dressing materials comprised of carboxymethylcellulose sodium or calcium alginate, which points toward their protective function against mechanical stress. Coating with hydrophobic poly(dimethylsiloxane) (applied to favor nanofiber removal from the wound surface) impacted porosity and decreased both mechanical properties and adherence to excised human skin, though the obtained values were comparable to those attained for commercial hydrofiber-like materials. In vitro cytotoxicity and irritancy studies showed biocompatibility and no skin irritant response of nanofibers in contact with a reconstituted three-dimensional human skin model, while scratch assay using human fibroblast cell line HDFa revealed the valuable potential of CS/PEO nanofibers to promote cell migration at an early stage of injury.

Rapid endothelialization helps overcome the limitations of small-diameter vascular grafts. To develop biomimetic non-thrombogenic coatings supporting endothelialization, medical-grade polyurethane (PU) nanofibrous mats and tubular scaffolds with a diameter below 6 mm prepared by solution blow spinning were coated with polydopamine (PDA), or PDA and gelatin (PDA/Gel). The scaffolds were characterized by scanning electron microscopy, porosity measurement, tensile testing, wettability, Fourier Transform Infrared spectroscopy, and termogravimetric analysis, followed by the measurement of coating stability on the tubular scaffolds. The effect of coating on scaffold endothelialization and hemocompatibility was evaluated using human umbilical vein endothelial cells (HUVECs) and human platelets, showing low numbers of adhering platelets and significantly higher numbers of HUVECs on PDA- and PDA/Gel-coated mats compared to control samples. Tubular PU scaffolds and commercial ePTFE prostheses coated with PDA or PDA/Gel were colonized with HUVECs using radial magnetic cell seeding. PDA/Gel-coated samples achieved full endothelial coverage within 1-3 days post-endothelialization. Altogether, PDA and PDA/Gel coating significantly enhance the endothelialization on the flat surfaces, tubular small-diameter scaffolds, and commercial vascular prostheses. The presented approach constitutes a fast and efficient method of improving scaffold colonization with endothelial cells, expected to work equally well upon implantation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)