Preclinical Testing of Living Tissue-Engineered Heart Valves for Pediatric Patients, Challenges and Opportunities

Introduction: Pediatric patients with cardiac congenital diseases require heart valve implants that can grow with their natural somatic increase in size. Current artificial valves perform poorly in children and cannot grow; thus, living-tissue-engineered valves capable of sustaining matrix homeostasis could overcome the current drawbacks of artificial prostheses and minimize the need for repeat surgeries. Materials and Methods: To prepare living-tissue-engineered valves, we produced completely acellular ovine pulmonary valves by perfusion. We then collected autologous adipose tissue, isolated stem cells, and differentiated them into fibroblasts and separately into endothelial cells. We seeded the fibroblasts in the cusp interstitium and onto the root adventitia and the endothelial cells inside the lumen, conditioned the living valves in dedicated pulmonary heart valve bioreactors, and pursued orthotopic implantation of autologous cell-seeded valves with 6 months follow-up. Unseeded valves served as controls. Results: Perfusion decellularization yielded acellular pulmonary valves that were stable, no degradable in vivo, cell friendly and biocompatible, had excellent hemodynamics, were not immunogenic or inflammatory, non thrombogenic, did not calcify in juvenile sheep, and served as substrates for cell repopulation. Autologous adipose-derived stem cells were easy to isolate and differentiate into fibroblasts and endothelial-like cells. Cell-seeded valves exhibited preserved viability after progressive bioreactor conditioning and functioned well in vivo for 6 months. At explantation, the implants and anastomoses were intact, and the valve root was well integrated into host tissues; valve leaflets were unchanged in size, non fibrotic, supple, and functional. Numerous cells positive for a-smooth muscle cell actin were found mostly in the sinus, base, and the fibrosa of the leaflets, and most surfaces were covered by endothelial cells, indicating a strong potential for repopulation of the scaffold. Conclusions: Tissue-engineered living valves can be generated in vitro using the approach described here. The technology is not trivial and can provide numerous challenges and opportunities, which are discussed in detail in this paper. Overall, we concluded that cell seeding did not negatively affect tissue-engineered heart valve (TEHV) performance as they exhibited as good hemodynamic performance as acellular valves in this model. Further understanding of cell fate after implantation and the timeline of repopulation of acellular scaffolds will help us evaluate the translational potential of this technology

Robust OCC System Optimized for Low-Frame-Rate Receivers

Light emitting diodes (LED) are becoming the dominant lighting elements due to their efficiency. Optical camera communications (OCC), the branch of visible light communications (VLC) that uses video cameras as receivers, is a suitable candidate in facilitating the development of new communication solutions for the broader public because video cameras are available on almost any smartphone nowadays. Unfortunately, most OCC systems that have been proposed until now require either expensive and specialized high-frame-rate cameras as receivers, which are unavailable on smartphones, or they rely on the rolling shutter effect, being sensitive to camera movement and pointing direction, they produce light flicker when low-frame-rate cameras are used, or they must discern between more than two light intensity values, affecting the robustness of the decoding process. This paper presents in detail the design of an OCC system that overcomes these limitations, being designed for receivers capturing 120 frames per second and being easily adaptable for any other frame rate. The system does not rely on the rolling shutter effect, thus making it insensitive to camera movement during frame acquisition and less demanding about camera resolution. It can work with reflected light, requiring neither a direct line of sight to the light source nor high resolution image sensors. The proposed communication is invariant to the moment when the transmitter and the receiver are started as the communication is self-synchronized, without any other exchange of information between the transmitter and the receiver, without producing light flicker, and requires only two levels of brightness to be detected (light on and light off). The proposed system overcomes the challenge of not producing light flicker even when it is adapted to work with very low-frame-rate receivers. This paper presents the statistical analysis of the communication performance and discusses its implementation in an indoor localization system

Sonic Watermarking Method for Ensuring the Integrity of Audio Recordings

Methods for inspecting the integrity of audio recordings become a necessity. The evolution of technology allowed the manufacturing of small, performant, recording devices and significantly decreased the difficulty of audio editing. Any person that participates in a conversation can secretly record it, obtaining their own version of the audio captured using their personal device. The recordings can be easily edited afterwards to change the meaning of the message. The challenge is to prove if recordings were tampered with or not. A reliable solution for this was the highly acclaimed Electrical Network Frequency (ENF) criterion. Newer recording devices are built to avoid picking up the electrical network signal because, from the audio content point of view, it represents noise. Thus, the classic ENF criterion becomes less effective for recordings made with newer devices. The paper describes a novel sonic watermarking (i.e., the watermark is acoustically summed with the dialogue) solution, based on an ambient sound that can be easily controlled and is not suspicious to listeners: the ticking of a clock. This signal is used as a masker for frequency-swept (chirp) signals that are used to encode the ENF and embed it into all the recordings made in a room. The ENF embedded using the proposed watermark solution can be extracted and checked at any later moment to determine if a recording has been tampered with, thus allowing the use of the ENF criterion principles in checking the recordings made with newer devices. The experiments highlight that the method offers very good results in ordinary real-world conditions

The Importance of HDL-Cholesterol and Fat-Free Percentage as Protective Markers in Risk Factor Hierarchy for Patients with Metabolic Syndrome

This research focused on establishing a hierarchy concerning the influence of various biological markers and body composition parameters on preventing, diagnosing and managing Metabolic Syndrome (MetS). Our cross-sectional cohort study included 104 subjects without any atherosclerotic antecedent pathology, organized in two groups (with and without MetS). All participants underwent clinical and anthropometric measurements, DEXA investigation and blood tests for all MetS criteria, together with adiponectin, leptin, insulin, uric acid and CRP. Based on mathematical logic, we calculated a normalized sensitivity score to compare the predictive power of biomarkers and parameters associated with MetS, upon the prevalence of MetS. Patients with MetS report higher levels of uric acid (p = 0.02), CRP (p = 0.012) and lower levels of adiponectin (p = 0.025) than patients without MetS. The top three biological markers with the highest predictive power of the prevalence of the disease are HDL, insulin, and adiponectin:leptin ratio, and the top three body composition parameters are trunk fat-free percentage, waist-height ratio and trunk fat percentage. Their high sensitivity scores differentiate them from all the other markers analysed in the study. Our findings report relevant scores for estimating the importance of cardiometabolic risks in the prevalence of MetS. The high rank of protective markers, HDL and trunk fat-free percentage, suggest that positive effects have a stronger association with the prevalence of MetS, than negative ones do. Therefore, this risk stratification study provides important support for prevention and management programs regarding MetS

Pulmonary heart valve replacement using stabilized acellular xenogeneic scaffolds; effects of seeding with autologous stem cells

Background: We hypothesized that an ideal heart valve replacement would be acellular valve root scaffolds seeded with autologous stem cells. To test this hypothesis, we prepared porcine acellular pulmonary valves, seeded them with autologous adipose derived stem cells (ADSCs) and implanted them in sheep and compared them to acellular valves