Ureteral stents are broadly used for the treatment of a wide range of pathologies, with different complexities and characteristics. Despite being efficient, the morbidity associated with stents, such as bacterial infection and pain, limits their therapeutic action and often represents an increase in healthcare costs. As no single solution fits all problems, there is still a need to improve these medical devices. Throughout this review, the most recent innovations are outlined and suggestions regarding future directions for ureteral stent technology are formulated with respect to materials, coatings, and designs of these devices. As highlighted here, during the process of passing these innovations to the growing market of ureteral stents, one of the biggest challenges is to increase the predictive value of the in vitro assays and, consequently, reduce the number of in vivo tests needed. Thus, recommendations concerning in vitro standard testing of these devices are provided, with focus on medium, flow conditions, and microbiological parameters. Additionally, the reader is also presented with insights about a crucial but rarely discussed topic, the bureaucratic part of the bench to market process, particularly the product certification legislation in Europe.
Extracellular matrix (ECM)-based bioinks have been steadily gaining interest in the field of bioprinting to develop biologically relevant and functional tissue constructs. Herein, we propose the use of supercritical carbon dioxide (scCO2) technology to extract the ECM components of cell-sheets that have shown promising results in creating accurate 3D microenvironments replicating the cell’s own ECM, to be used in the preparation of bioinks. The ECM extraction protocol best fitted for cell sheets was defined by considering efficient DNA removal with a minor effect on the ECM. Cell sheets of human dermal fibroblasts (hDFbs) and adipose stem cells (hASCs) were processed using a customised supercritical system by varying the pressure of the reactor, presence, exposure time, and type of co-solvent. A quantification of the amount of DNA, protein, and sulfated glycosaminoglycans (sGAGs) was carried out to determine the efficiency of the extraction in relation to standard decellularization methodologies. The bioinks containing the extracted ECM were fabricated by combining them with alginate as a support polymer. The influence of the alginate (1%, 2% w/vol) and ECM (0.5% and 1.5% w/vol) amounts on the printability of the blends was addressed by analysing the rheological behaviour of the suspensions. Finally, 3D printed constructs were fabricated using an in-house built extrusion-based bioprinter, and the impact of the extrusion process on cell viability was assessed. The optimised scCO2 protocol allowed efficient removal of DNA while preserving a higher number of proteins and sGAGs than the standard methodologies. The characterization of extract’s composition also revealed that the ECM produced by hDFbs (fECM) and hASCs (aECM) is distinctively affected by the extraction protocols. Furthermore, rheological analysis indicated an increase in viscosity with increasing ECM composition, an effect even more prominent in samples containing aECM. 3D printing of alginate/ECM constructs demonstrated that cell viability was only marginally affected by the extrusion process, and this effect was also dependent on the ECM source. Overall, this work highlights the benefits of supercritical fluid-based methods for ECM extraction and strengthens the relevance of ECM-derived bioinks in the development of printed tissue-like constructs.
Urinary stent coatings are a strategy to tackle certain complications associated with the use of biomaterials. The latest innovations in surface coatings focused on the prevention of those problems, thus reducing further costs with treatments. Urinary stents associated symptoms, infections and encrustation are considered the major challenges, and, in an attempt to prevent such morbidity, several strategies were developed. Hence, coatings have been designed to improve quality of life for patients, reducing the friction, inhibiting uropathogens survival or attachment on stents, and avoiding the deposition of urinary crystals that triggers encrustation. Currently for ureteral stents, hydrophilic and diamond-like carbon coatings are commercial options associated with an enhanced performance of devices, comparing with uncoated ones. These commercially available approaches are all anti-adhesive coatings, and, in the general overview, this type of strategy appears to be a superior alternative than bactericidal coatings. Designs that trigger uropathogen death are usually associated with higher toxicity, and, in some cases, it can even favor the development of microbial resistance, which can hamper the infection treatment. With the present knowledge about antimicrobial mechanisms and inspired by nature, more cutting-edge alternatives, able to confer antimicrobial properties to the inner and outer parts of stents, will surely appear.
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