Design, manufacturing and testing of a green non-isocyanate polyurethane prosthetic heart valve.

The sole effective treatment for most patients with heart valve disease is valve replacement by implantation of mechanical or biological prostheses. However, mechanical valves represent high risk of thromboembolism, and biological prostheses are prone to early degeneration. In this work, we aim to determine the potential of novel environmentally-friendly non-isocyanate polyurethanes (NIPUs) for manufacturing synthetic prosthetic heart valves. Polyhydroxyurethane (PHU) NIPUs are synthesized via an isocyanate-free route, tested in vitro, and used to produce aortic valves. PHU elastomers reinforced with a polyester mesh show mechanical properties similar to native valve leaflets. These NIPUs do not cause hemolysis. Interestingly, both platelet adhesion and contact activation-induced coagulation are strongly reduced on NIPU surfaces, indicating low thrombogenicity. Fibroblasts and endothelial cells maintain normal growth and shape after indirect contact with NIPUs. Fluid-structure interaction (FSI) allows modeling of the ideal valve design, with minimal shear stress on the leaflets. Injection-molded valves are tested in a pulse duplicator and show ISO-compliant hydrodynamic performance, comparable to clinically-used bioprostheses. Poly(tetrahydrofuran) (PTHF)-NIPU patches do not show any evidence of calcification over a period of 8 weeks. NIPUs are promising sustainable biomaterials for the manufacturing of improved prosthetic valves with low thrombogenicity.

Design of 3D-Photoprintable, Bio-, and Hemocompatible Nonisocyanate Polyurethane Elastomers for Biomedical Implants.

Polyurethanes (PUs) have adjustable mechanical properties, making them suitable for a wide range of applications, including in the biomedical field. Historically, these PUs have been synthesized from isocyanates, which are toxic compounds to handle. This has encouraged the search for safer and more environmentally friendly synthetic routes, leading today to the production of nonisocyanate polyurethanes (NIPUs). Among these NIPUs, polyhydroxyurethanes (PHUs) bear additional hydroxyl groups, which are particularly attractive for derivatizing and adjusting their physicochemical properties. In this paper, polyether-based NIPU elastomers with variable stiffness are designed by functionalizing the hydroxyl groups of a poly(propylene glycol)-PHU by a cyclic carbonate carrying a pendant unsaturation, enabling them to be post-photo-cross-linked with polythiols (thiol-ene). Elastomers with remarkable mechanical properties whose stiffness can be adjusted are obtained. Thanks to the unique viscous properties of these PHU derivatives and their short gel times observed by rheology experiments, formulations for light-based three-dimensional (3D) printing have been developed. Objects were 3D-printed by digital light processing with a resolution down to the micrometer scale, demonstrating their ability to target various designs of prime importance for personalized medicine. In vitro biocompatibility tests have confirmed the noncytotoxicity of these materials for human fibroblasts. In vitro hemocompatibility tests have revealed that they do not induce hemolytic effects, they do not increase platelet adhesion, nor activate coagulation, demonstrating their potential for future applications in the cardiovascular field.

Optimal Global Longitudinal Strain Thresholds for Pediatric Heart Surgery: Insights from a University Hospital.

Congenital heart diseases impact millions annually, with pediatric care lacking suitable risk assessment tools. This research seeks to illuminate the association between the global longitudinal strain (GLS) and the subsequent impact on postoperative outcomes, contributing to a deeper understanding of its predictive value in the pediatric population affected by congenital heart diseases. An observational, analytic, longitudinal, and prospective study was conducted from May 2022 to May 2023, including all patients under 18 undergoing heart surgery with cardiopulmonary bypass (CBP). Patients not classifiable within the Risk Adjustment for Congenital Heart Surgery were excluded. Using transesophageal echocardiography, GLS was measured pre- and post-CPB. Receiver operating characteristic curve analysis determined GLS cut-off points for 30-day mortality risk, using Youden's method for optimal sensitivity and specificity. Bivariate and multivariate analysis identified the relationships between clinical variables. Eighty-nine patients undergoing congenital heart surgery were included. Fifteen deaths occurred. The area under the curve (AUC) for each GLS classification (pre, post, index) demonstrated effective discriminatory capacity (> 0.70) in predicting 30-day mortality. Pre-CBP GLS showed the strongest predictive power (AUC 0.833, IQR: 0.731 - 0.936) with a cut-off point of 12. Values lower than the cut-off point of pre-CPB GLS correlated with increased vasoactive-inotropic Scores and longer mechanical ventilation. GLS measurement is a reproducible method for assessing ventricular function in pediatric heart surgery, showing potential as a prognostic tool. This study marks the initial effort to establish cut-off points for preoperative GLS, postoperative GLS, and the strain index.

Graphene Oxide Coating Improves the Mechanical and Biological Properties of Decellularized Umbilical Cord Arteries.

The lack of small-diameter vascular grafts (inner diameter <5 mm) to substitute autologous grafts in arterial bypass surgeries has a massive impact on the prognosis and progression of cardiovascular diseases, the leading cause of death globally. Decellularized arteries from different sources have been proposed as an alternative, but their poor mechanical performance and high collagen exposure, which promotes platelet and bacteria adhesion, limit their successful application. In this study, these limitations were surpassed for decellularized umbilical cord arteries through the coating of their lumen with graphene oxide (GO). Placental and umbilical cord arteries were decellularized and perfused with a suspension of GO (C/O ratio 2:1) with ∼1.5 µm lateral size. A homogeneous GO coating that completely covered the collagen fibers was obtained for both arteries, with improvement of mechanical properties being achieved for umbilical cord decellularized arteries. GO coating increased the maximum force in 27%, the burst pressure in 29%, the strain in 25%, and the compliance in 10%, compared to umbilical cord decellularized arteries. The achieved theoretical burst pressure (1960 mmHg) and compliance (13.9%/100 mmHg) are similar to the human saphenous vein and mammary artery, respectively, which are used nowadays as the gold standard in coronary and peripheral artery bypass surgeries. Furthermore, and very importantly, coatings with GO did not compromise the endothelial cell adhesion but decreased platelet and bacteria adhesion to decellularized arteries, which will impact on the prevention of thrombosis and infection, until full re-endothetialization is achieved. Overall, our results reveal that GO coating has an effective role in the improvement of decellularized umbilical cord artery performance, which is a huge step toward their application as a small-diameter vascular graft.

Incorporation of graphene oxide into poly(ɛ-caprolactone) 3D printed fibrous scaffolds improves their antimicrobial properties.

Implantable medical devices infection and consequent failure is a severe health issue, which can result from bacterial adhesion, growth, and subsequent biofilm formation at the implantation site. Graphene-based materials, namely graphene oxide (GO), have been described as potential antibacterial agents when immobilized and exposed in polymeric matrices. This work focuses on the development of antibacterial and biocompatible 3D fibrous scaffolds incorporating GO. Poly(ε-caprolactone) scaffolds were produced, with and without GO, using wet-spinning combined with additive manufacturing. Scaffolds with different GO loadings were evaluated regarding physical-chemical characterization, namely GO surface exposure, antibacterial properties, and ability to promote human cells adhesion. Antimicrobial properties were evaluated through live/dead assays performed with Gram-positive and Gram-negative bacteria. 2 h and 24 h adhesion assays revealed a time-dependent bactericidal effect in the presence of GO, with death rates of adherent S. epidermidis and E. coli reaching ~80% after 24 h of contact with scaffolds with the highest GO concentration. Human fibroblasts cultured for up to 14 days were able to adhere and spread over the fibers, independently of the presence of GO. Overall, this work demonstrates the potential of GO-containing fibrous scaffolds to be used as biomaterials that hinder bacterial infection, while allowing human cells adhesion.

Phakic Intraocular Lens Implantation: Refractive Outcome and Safety in Patients with Anterior Chamber Depth between 2.8 and 3.0 versus ≥3.0 mm.

PURPOSE: To compare endothelial cell (EC) variation after anterior chamber phakic intraocular lens (AC-pIOL) implantation in highly myopic patients with a preoperative anterior chamber depth (ACD) between 2.8 and 3.0 versus ≥3.0 mm. METHODS: A total of 280 eyes submitted to primary AC-pIOL implantation were analyzed. Pre- and postoperative values for uncorrected distance visual acuity, corrected distance visual acuity, spherical equivalent, ACD (endothelial surface), and EC count were collected. The eyes were divided into 2 groups: group A - ACD between 2.8 and 3.0 mm; group B - ACD ≥3.0 mm. Mean global EC loss (ECL) and loss for each ACD group, according to pIOL type, were analyzed. RESULTS: Significant improvement of the spherical equivalent (-11.38 ± 4.57 vs. -0.49 ± 0.79; p = 0.000) and a significant decrease in EC density (2,810.95 ± 343.88 vs. 2,584.09 ± 374.88 cells/mm2; p = 0.000) were noted. The mean annual ECL was -2.19 ± 3.97%. Regarding group A (n = 80), a mean annual ECL of -2.06 ± 3.88% was registered, higher for the Acrysof Cachet® subtype, while group B (n = 200) showed -2.25 ± 4.01% ECL, higher for the Verisyse® subtype. There was no significant difference between the groups (p = 0.96). CONCLUSIONS: AC-pIOL implantation significantly improves the spherical equivalent in myopic patients. The mean annual ECL after pIOL implantation was higher in the larger ACD group, but this value was not statistically significant. A 2.8-mm ACD value seems to be a safe cutoff for AC-pIOL implantation.

Transplante renal: a influência da terapia imunosupressora na prevalência de manifestações estomatológicas / Renal transplant: the influence of the immunosuppressive therapy in the prevalence of stomatologic manifestations

Os autores, após dimensionarem o problema da rejeição pós-transplante renal, fazem uma revisão, sob a ótica do cirurgião-dentista, a respeito da terapia imunossupressora e sua influência nas manifestações estomatológicas. No texto são ressaltados a importância do conhecimento da prevalência dessas lesões orais associadas ao transplante renal e o uso de medicações, para um correto estabelecimento a respeito da origem de tais lesões