Biomechanical effects of hemin and sildenafil treatments on the aortic wall of chronic-hypoxic lambs.

Introduction: Gestation under chronic hypoxia causes pulmonary hypertension, cardiovascular remodeling, and increased aortic stiffness in the offspring. To mitigate the neonatal cardiovascular risk, pharmacological treatments (such as hemin and sildenafil) have been proposed to improve pulmonary vasodilation. However, little is known about the effects of these treatments on the aorta. Therefore, we studied the effect of hemin and sildenafil treatments in the aorta of lambs gestated and raised at highlands, thereby subjected to chronic hypoxia. Methods: Several biomechanical tests were conducted in the descending thoracic aorta (DTA) and the distal abdominal aorta (DAA), assessing 3 groups of study of hypoxic animals: non-treated (Control) and treated either with hemin or sildenafil. Based on them, the stiffness level has been quantified in both zones, along with the physiological strain in the unloaded aortic duct. Furthermore, a morphological study by histology was conducted in the DTA. Results: Biomechanical results indicate that treatments trigger an increment of axial pre-stress and circumferential residual stress levels in DTA and DAA of lambs exposed to high-altitude chronic hypoxia, which reveals a vasodilatation improvement along with an anti-hypertensive response under this characteristic environmental condition. In addition, histological findings do not reveal significant differences in either structure or microstructural content. Discussion: The biomechanics approach emerges as a valuable study perspective, providing insights to explain the physiological mechanisms of vascular function. According to established results, alterations in the function of the aortic wall may not necessarily be explained by morphostructural changes, but rather by the characteristic mechanical state of the microstructural components that are part of the studied tissue. In this sense, the reported biomechanical changes are beneficial in mitigating the adverse effects of hypobaric hypoxia exposure during gestation and early postnatal life.

Synthesis, Characterization and Catechol-Based Bioinspired Adhesive Properties in Wet Medium of Poly(2-Hydroxyethyl Methacrylate-co-Acrylamide) Hydrogels.

Hydrogels consist of crosslinked hydrophilic polymers from which their mechanical properties can be modulated for a wide variety of applications. In the last decade, many catechol-based bioinspired adhesives have been developed following the strategy of incorporating catechol moieties into polymeric backbones. In this work, in order to further investigate the adhesive properties of hydrogels and their potential advantages, several hydrogels based on poly(2-hydroxyethyl methacrylate-co-acrylamide) with N'N-methylene-bisacrylamide (MBA), without/with L-3,4-dihydroxyphenylalanine (DOPA) as a catecholic crosslinker, were prepared via free radical copolymerization. 2-Hydroxyethyl methacrylate (HEMA) and acrylamide (AAm) were used as comonomers and MBA and DOPA both as crosslinking agents at 0.1, 0.3, and 0.5 mol.-%, respectively. The polymeric hydrogels were characterized by Fourier transform infrared spectroscopy (FT-IR), thermal analysis and swelling behavior analysis. Subsequently, the mechanical properties of hydrogels were determined. The elastic properties of the hydrogels were quantified using Young's modulus (stress-strain curves). According to the results herein, the hydrogel with a feed monomer ratio of 1:1 at 0.3 mol.-% of MBA and DOPA displayed the highest rigidity and higher failure shear stress (greater adhesive properties). In addition, the fracture lap shear strength of the biomimetic polymeric hydrogel was eight times higher than the initial one (only containing MBA); however at 0.5 mol.-% MBA/DOPA, it was only two times higher. It is understood that when two polymer surfaces are brought into close contact, physical self-bonding (Van der Waals forces) at the interface may occur in an -OH interaction with wet contacting surfaces. The hydrogels with DOPA provided an enhancement in the flexibility compared to unmodified hydrogels, alongside reduced swelling behavior on the biomimetic hydrogels. This approach expands the possible applications of hydrogels as adhesive materials, in wet conditions, within scaffolds that are commonly used as biomaterials in cartilage tissue engineering.

Analysis of the geometrical influence of ring-opening samples on arterial circumferential residual stress reconstruction.

This work consists of analyzing the impact of geometrical features (thickness and curvature) on the estimation of circumferential residual stresses in arteries. For this purpose, a specific sample of lamb abdominal artery is chosen for analysis and, through computational tools based on Python libraries, the stress-free geometry is captured after the ring opening test. Numerical simulations are then used to reconstruct the sample in order to estimate the circumferential residual stresses. Then, four stress-free geometry models are analyzed: an ideal geometry, i.e., constant curvature and thickness; a constant curvature and variable thickness geometry; a variable curvature and constant thickness geometry; and a variable curvature and thickness geometry. The numerical results show that models perform well from a geometric point of view, where the most different feature was the closed outer perimeter that differs about 14% from the closed real sample. As far as residual stress is concerned, differences up to 198% were found in more realistic models taking a constant curvature and thickness model as reference. Thus, the analysis of a realistic geometry with highly variable curvature and thickness can introduce, compared to an idealized geometry, significant differences in the estimation of residual stresses. This could indicate that the characterization of arterial residual stresses is not sufficient when considering only the opening angle and, therefore, it is also necessary to incorporate more geometrical variables.