Time-dependent mechanical behavior of human amnion: Macroscopic and microscopic characterization

Characterizing the mechanical response of the human amnion is essential to understand and to eventually prevent premature rupture of fetal membranes. In this study, a large set of macroscopic and microscopic mechanical tests have been carried out on fresh unfixed amnion to gain insight into the time-dependent material response and the underlying mechanisms. Creep and relaxation responses of amnion were characterized in macroscopic uniaxial tension, biaxial tension and inflation configurations. For the first time, these experiments were complemented by microstructural information from nonlinear laser scanning microscopy performed during in situ uniaxial relaxation tests. The amnion showed large tension reduction during relaxation and small inelastic strain accumulation in creep. The short-term relaxation response was related to a concomitant in-plane and out-of-plane contraction, and was dependent on the testing configuration. The microscopic investigation revealed a large volume reduction at the beginning, but no change of volume was measured long-term during relaxation. Tension–strain curves normalized with respect to the maximum strain were highly repeatable in all configurations and allowed the quantification of corresponding characteristic parameters. The present data indicate that dissipative behavior of human amnion is related to two mechanisms: (i) volume reduction due to water outflow (up to ∼20 s) and (ii) long-term dissipative behavior without macroscopic deformation and no systematic global reorientation of collagen fibers

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

A comparative investigation of mussel-mimetic sealants for fetal membrane repair

Towards the prevention of iatrogenic preterm premature rupture of the fetal membrane, two mussel-mimetic tissue adhesives (cT and cPEG) have been compared and qualified as possible sealants for membrane repair. Monotonic and cyclic inflation tests of repaired fetal membranes were carried out in order to investigate the performance of the glues under quasi-static, fast, and repeated loading. Finite element simulations of repaired and inflated synthetic membranes allowed to compare cT and cPEG under large deformations. Both adhesives seal the membrane well, resisting pressures higher than the intra-uterine baseline. Only under repeated mechanical load, as well as under fast and acute deformation of the membrane, the sealing performance has deteriorated. Even though cT loses adhesion to the deformed membrane, it is able to withstand high deformations and pressures without rupturing, while cPEG breaks

Mechanical and microstructural investigation of the cyclic behavior of human amnion

The structural and mechanical integrity of amnion is essential to prevent preterm premature rupture (PPROM) of the fetal membrane. In this study, the mechanical response of human amnion to repeated loading and the microstructural mechanisms determining its behavior were investigated. Inflation and uniaxial cyclic tests were combined with corresponding in situ experiments in a multiphoton microscope (MPM). Fresh unfixed amnion was imaged during loading and changes in thickness and collagen orientation were quantified. Mechanical and in situ experiments revealed differences between the investigated configurations in the deformation and microstructural mechanisms. Repeated inflation induces a significant but reversible volume change and is characterized by high energy dissipation. Under uniaxial tension, volume reduction is associated with low energy, unrecoverable in-plane fiber reorientation

Contractions, a risk for premature rupture of fetal membranes: A new protocol with cyclic biaxial tension

This study aims at investigating the effect of repeated mechanical loading on the rupture and deformation properties of fetal membranes. Ten membranes delivered by cesarean sections were tested using a custom-built inflation device which provides a multi-axial stress state. For each membrane, a group of samples was first cyclically stretched by application of pressure ranging between 10 and 40mmHg. After cycles, samples were subjected to inflation up to rupture. Differences between mechanical parameters from cycled and uncycled samples were analyzed. Ten cycles at 40% of mean critical membrane tension-representative of mean physiologic contractions-did not affect strength and stiffness of fetal membranes but reduced the work to rupture, thus indicating that contractions might increase the risk of premature rupture of the membrane. Cyclic testing demonstrated a large hysteresis loop and irreversible deformation on the first cycle, followed by rapid stabilization on subsequent cycles. In 80% of tests, amnion ruptured first and at the periphery of the sample, under uniaxial strain state. Chorion ruptured at higher deformation levels in the middle, under biaxial strain state

A novel bioreactor system for the assessment of endothelialization on deformable surfaces

The generation of a living protective layer at the luminal surface of cardiovascular devices, composed of an autologous functional endothelium, represents the ideal solution to life-threatening, implant-related complications in cardiovascular patients. The initial evaluation of engineering strategies fostering endothelial cell adhesion and proliferation as well as the long-term tissue homeostasis requires in vitro testing in environmental model systems able to recapitulate the hemodynamic conditions experienced at the blood-to-device interface of implants as well as the substrate deformation. Here, we introduce the design and validation of a novel bioreactor system which enables the long-term conditioning of human endothelial cells interacting with artificial materials under dynamic combinations of flow-generated wall shear stress and wall deformation. The wall shear stress and wall deformation values obtained encompass both the physiological and supraphysiological range. They are determined through separate actuation systems which are controlled based on validated computational models. In addition, we demonstrate the good optical conductivity of the system permitting online monitoring of cell activities through live-cell imaging as well as standard biochemical post-processing. Altogether, the bioreactor system defines an unprecedented testing hub for potential strategies toward the endothelialization or re-endothelialization of target substrates.ISSN:2045-232