Hydrogels from natural polymers such as sodium alginate have great potential in regenerative medicine because of their biocompatibility, biodegradability, mechanical properties, bioresorption ...ability, and relatively low cost. Sodium alginate, a polysaccharide derived from brown seaweed, is the most widely investigated and used biomaterial in biomedical applications. Alginate dressings are also useful as a delivery platform in order to provide a controlled release of therapeutic substances (e.g., pain-relieving, antibacterial, and anti-inflammatory agents). In our work, we aimed to analyze process of degradation of alginate hydrogels. We also describe an original hybrid crosslinking process by using not one, as usual, but a mixture of two crosslinking agents (calcium chloride and barium chloride). We proved that different crosslinking agents allow producing hydrogels with a spectrum of mechanical properties, similar to the urethra tissue. Hydrogels were formed using a dip-coating technique, and then examined by mechanical testing, FTIR (Fourier-Transform Infrared Spectroscopy), and resorption on artificial urine. Obtained hydrogels have a different degradation rate in artificial urine, and they can be used as a material for healing of urethra injuries, especially urethra strictures, which significantly affect the quality of life of patients.
The search for ideal solutions for the treatment of urethral stenosis continues. This includes developing the material, design, while maintaining its optimal and desired properties. This paper ...presents the results of the research conducted on sodium alginate-based hydrogel material (AHM), which may be used as a material for stents dedicated to the treatment of pathologies occurring in the genitourinary system. In order to determine the selected parameters of the AHM samples, strength and degradation tests, as well as analysis of the micro changes occurring on the surface of the material using a digital image correlation (µDIC) system, were performed. This study shows that the material possessed good mechanical strength parameters, the knowledge of which is particularly important from the point of view of the stent-tissue interaction. The degradation analysis performed showed that the AHM samples degrade in an artificial urine environment, and that the degradation time mainly depends on the chemical composition of the material. The novel µDIC method performed allowed us to characterize the homogeneity of the material structure depending on the cross-linking agent used.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
New hydrogel materials developed to improve soft tissue healing are an alternative for medical applications, such as tissue regeneration or enhancing the biotolerance effect in the ...tissue-implant–body fluid system. The biggest advantages of hydrogel materials are the presence of a large amount of water and a polymeric structure that corresponds to the extracellular matrix, which allows to create healing conditions similar to physiological ones. The present work deals with the change in mechanical properties of sodium alginate mixed with gelatin containing Pygeum africanum. The work primarily concentrates on the evaluation of the mechanical properties of the hydrogel materials produced by the sol–gel method. The antimicrobial activity of the hydrogels was investigated based on the population growth dynamics of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923, as well as the degree of degradation after contact with urine using an innovative method with a urine flow simulation stand. On the basis of mechanical tests, it was found that sodium alginate-based hydrogels with gelatin showed weaker mechanical properties than without the additive. In addition, gelatin accelerates the degradation process of the produced hydrogel materials. Antimicrobial studies have shown that the presence of African plum bark extract in the hydrogel enhances the inhibitory effect on Gram-positive and Gram-negative bacteria. The research topic was considered due to the increased demand from patients for medical devices to promote healing of urethral epithelial injuries in order to prevent the formation of urethral strictures.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background: Frequency of urethral stenosis makes it necessary to develop new innovative methods of treating this disease. This pathology most often occurs in men and manifests itself in painful ...urination, reduced urine flow, or total urinary retention. This is a condition that requires immediate medical intervention. Methods: Experimental tests were carried out on a rabbit in order to determine the changes of pressure in the urethra system and to estimate the velocity of urine flow. For this purpose, a measuring system was proposed to measure the pressure of a fluid-filled urethra. A fluoroscope was used to observe the deformability of the bladder and urethra canal. Results: Based on these tests, the range of changes in the urethra tube diameter, the pressures inside the system, and the flow velocity during micturition were determined. Conclusions: The presented studies allowed determining the behavior of the urethra under the conditions of urinary filling. The fluid-filled bladder and urethra increased their dimensions significantly. Such large changes require that the stents used for the treatment of urethral stenosis should not have a fixed diameter but should adapt to changing urethral dimensions.
The paper contains the results of the analysis of sodium alginate use as a material for making urethral stents, necessary for the treatment of urinary disorders. Strength tests of the material were ...carried out, analyzing the characteristics of the material in terms of its interaction with the urethra. The characteristics of the urethra, which is characterized by large deformations, were investigated experimentally. Based on the results of the experiments, geometric dimensions of the stent were developed. According to the results obtained, stent structure was developed, which was implanted into the rabbit urethra. The in vivo study confirmed the assumptions. The implanted stent was effectively and without damage expanded inside the urethra within the assumed diameter variation limits, free flow of urine during the urination was obtained after the implantation, and the proposed design fulfilled the strength assumptions resulting from the pressure of the urethra walls on the stent surface.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The mitral valve apparatus is a complex structure consisting of the mitral ring, valve leaflets, papillary muscles and Chordae tendineae (CT). The latter are mainly responsible for the mechanical ...functions of the valve. Our study included investigations of the biomechanical and structural properties of CT collected from canine and porcine hearts, as there are no studies about these properties of canine CT. We performed a static uniaxial tensile test on CT samples and a histopathological analysis in order to examine their microstructure. The results were analyzed to clarify whether the changes in mechanical persistence of Chordae tendineae are combined with the alterations in their structure. This study offers clinical insight for future research, allowing for an understanding of the process of Chordae tendineae rupture that happens during degenerative mitral valve disease—the most common heart disease in dogs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Endotoxin tolerance, the transient, secondary down-regulation of a subset of endotoxin-driven responses after exposure to bacterial products, is thought to be an adaptive response providing ...protection from pathological hyperactivation of the innate immune system during bacterial infection. However, although protecting from the development of sepsis, endotoxin tolerance also can lead to fatal blunting of immunological responses to subsequent infections in survivors of septic shock. Despite considerable experimental effort aimed at characterizing the molecular mechanisms responsible for a variety of endotoxin tolerance-related phenomena, no consensus has been achieved yet. IL-12 is a macrophage- and dendritic cell (DC)-derived cytokine that plays a key role in pathological responses to endotoxin as well as in the induction of protective responses to pathogens. It recently has been shown that IL-12 production is suppressed in endotoxin tolerance, providing a likely partial mechanism for the increased risk of secondary infections in sepsis survivors. We examined the development of IL-12 suppression during endotoxin tolerance in mice. Decreased IL-12 production in vivo is clearly multifactorial, involving both loss of CD11c(high) DCs as well as alterations in the responsiveness of macrophages and remaining splenic DCs. We find no demonstrable mechanistic role for B or T lymphocytes, the soluble mediators IL-10, TNF-alpha, IFN-alphabeta, or nitric oxide, or the NF-kappaB family members p50, p52, or RelB.
Approaches to limiting exposure to antiretroviral therapy (ART) drugs are an active area of HIV therapy research. Here we present longitudinal follow-up of a randomized, open-label, single-center ...study of the immune, viral, and safety outcomes of structured therapy interruptions (TIs) in patients with chronically suppressed HIV-1 infection as compared to equal follow-up of patients on continuous therapy and including a final therapy interruption in both arms.
Forty-two chronically HIV-infected patients on suppressive ART with CD4 counts higher than 400 were randomized 1:1 to either (1) three successive fixed TIs of 2, 4, and 6 wk, with intervening resumption of therapy with resuppression for 4 wk before subsequent interruption, or (2) 40 wk of continuous therapy, with a final open-ended TI in both treatment groups. Main outcome was analysis of the time to viral rebound (>5,000 copies/ml) during the open-ended TI. Secondary outcomes included study-defined safety criteria, viral resistance, therapy failure, and retention of immune reconstitution. There was no difference between the groups in time to viral rebound during the open-ended TI (continuous therapy/single TI, median interquartile range = 4 1-8 wk, n = 21; repeated TI, median interquartile range = 5 4-8 wk, n = 21; p = 0.36). No differences in study-related adverse events, viral set point at 12 or 20 wk of open-ended interruption, viral resistance or therapy failure, retention of CD4 T cell numbers on ART, or retention of lymphoproliferative recall antigen responses were noted between groups. Importantly, resistance detected shortly after initial viremia following the open-ended TI did not result in a lack of resuppression to less than 50 copies/ml after reinitiation of the same drug regimen.
Cycles of 2- to 6-wk time-fixed TIs in patients with suppressed HIV infection failed to confer a clinically significant benefit with regard to viral suppression off ART. Also, secondary analysis showed no difference between the two strategies in terms of safety, retention of immune reconstitution, and clinical therapy failure. Based on these findings, we suggest that further clinical research on the long-term consequences of TI strategies to decrease drug exposure is warranted.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The appropriate development and customisation of the stent to the urethral tissues requires the determination of many factors such as strength and degradation. Given the distinctive conditions of ...urethral tissues, it is important that the design of the stent be properly developed. The selection of a stent material requires knowing its material characteristics and verifying that they are suitable for the future implantation site. In the present study, the development of a polydioxanone (PDO)-based stent was undertaken. The PDO material was fabricated using an additive technique – 3D printing. Then, in vitro tests were performed to determine the degradation time of the material under conditions simulating an aggressive urinary environment. The changes in the parameters of mechanical properties before and after the degradation period were determined, and the changes in the structure of the material before and after degradation were observed. Numerical analysis was performed for the proposed stent design. The results showed that PDO has good mechanical properties, but its degradation time is too short to be used in a urethral stent. Among the innovations of the studies conducted are bending strength tests, which is not a frequently considered aspect so far.
The aim of the study was the histological and morphometrical evaluation of the urethral wall at three time points after bioresorbable stent implantation in male New Zealand White Rabbits. The ...research was performed on 26 male New Zealand White rabbits aged 3-4 months and weighing 2.1-3.0 kg. Two models of bioresorbable sodium alginate-based stents were developed and implanted into the urethral lumen for one (T1), three (T3), and six weeks (T6). Sections of 5 µm thickness were cut from the urethra at intervals of 2 mm. The sliced sections were stained with hematoxylin-eosin (H&E), Van Gieson's (VG), Von Kossa, and Movat-Russell modified pentachrome (MOVAT) staining methods. The study provided valuable information for future models of urethral stents. The first model of the stent failed to fit the requirements due to inadequate mechanical properties. It curled up on itself losing the ability to adhere to the animals' urethra and was bioresorbed three weeks after implantation. The more rigid no. 2 stent was effective in widening the urethral lumen but did not biodegrade during the experiment. A comprehensive assessment of the second model's properties of biosorption and biointegration requires an extended observation of at least 12 months for an in depth morphological analysis. Stent migration is not likely to be caused solely by the mechanical properties of the urethra or urinary flow but mainly by muscle contraction of the organ wall.
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