Design, construction and validation of a registering and analysis system for the electrophysiological properties of an isolated porcine heart model

Cardiac fibrillation is as a relevant subject of study in cardiovascular diseases. Its initiation mechanisms, maintenance and interruption processes are still partially misunderstood. Quantifying the complexity of electrocardiographic signals allows researchers to objectify induced modifications by a particular therapeutic treatment. With the aim to study alterations in the cardiac substrate, the objective of this project is to design, build and validate a real-time registering and analysis system for the electrophysiological properties of the epicardial and endocardial tissue of an isolated porcine heart model. We propose a functional computer user interface. We designed and implemented a platform capable of real-time quantifying electrocardiographic signals. The corresponding methodology consists of the use of a combination of time and frequency domain analysis algorithms divided in separate blocks that work together. While the first block detects the heart rhythm and ECG features according to a Pan and Tompkins based algorithm, the second block detects the fundamental frequency of the myocardial activations based on frequency analysis; and the third one detects ventricular fibrillation episodes based on a phase-space reconstruction of the signal. This system was tested by developing an electrocardiographic waveform simulator. We performed five ex-vivo experiments for validation of the platform using isolated porcine hearts in a Langendorff bioreactor, by means of a controlled backward perfusion of the coronary arteries. Whole-heart optical mapping was carried out as the gold standard, and comparisons between the off-line analysis of the optical recordings and real-time results obtained with the developed platform were made. Results showed that electrical signals registered with the developed platform were in accordance with dominant frequency maps obtained from the off-line analysis of the corresponding optical recordings. The developed platform was able to real-time differentiate onset of ventricular fibrillation events from sinus rhythm episodes, as well as automatically detect myocardial rhythm and fundamental frequency of myocardial activations. We conclude that the proposed system is a versatile tool that allows us to easily, quickly and automatically real-timely quantify in a reproducible way electrocardiographic recordings of isolated hearts in a Langendorff bioreactor. This, in turn, would help in the performance of various clinical applications: from ex-vivo studies of the cardiac substrate to the testing of potential antiarrhythmic drugs.Ingeniería Biomédic

Electroresponsive Silk-Based Biohybrid Composites for Electrochemically Controlled Growth Factor Delivery

Stimuli-responsive materials are very attractive candidates for on-demand drug delivery applications. Precise control over therapeutic agents in a local area is particularly enticing to regulate the biological repair process and promote tissue regeneration. Macromolecular therapeutics are difficult to embed for delivery, and achieving controlled release over long-term periods, which is required for tissue repair and regeneration, is challenging. Biohybrid composites incorporating natural biopolymers and electroconductive/active moieties are emerging as functional materials to be used as coatings, implants or scaffolds in regenerative medicine. Here, we report the development of electroresponsive biohybrid composites based on Bombyx mori silkworm fibroin and reduced graphene oxide that are electrostatically loaded with a high-molecular-weight therapeutic (i.e., 26 kDa nerve growth factor-β (NGF-β)). NGF-β-loaded composite films were shown to control the release of the drug over a 10-day period in a pulsatile fashion upon the on/off application of an electrical stimulus. The results shown here pave the way for personalized and biologically responsive scaffolds, coatings and implantable devices to be used in neural tissue engineering applications, and could be translated to other electrically sensitive tissues as well

Human airway-like multilayered tissue on 3D-TIPS printed thermoresponsive elastomer/collagen hybrid scaffolds

Developing a biologically representative complex tissue of the respiratory airway is challenging, however, beneficial for treatment of respiratory diseases, a common medical condition representing a leading cause of death in the world. This study reports a successful development of synthetic human tracheobronchial epithelium based on interpenetrated hierarchical networks composed of a reversely 3D printed porous structure of a thermoresponsive stiffness-softening elastomer nanohybrid impregnated with collagen nanofibrous hydrogel in vitro. Human bronchial epithelial cells (hBEpiCs) were able to attach and grow into an epithelial monolayer on the hybrid scaffolds co-cultured with either human bronchial fibroblasts (hBFs) or human bone-marrow derived mesenchymal stem cells (hBM-MSCs), with substantial enhancement of mucin expression, ciliation, well-constructed intercellular tight junctions and adherens junctions. The multi-layered co-culture 3D scaffolds consisting of a top monolayer of differentiated epithelium, with either hBFs or hBM-MSCs proliferating within the hyperelastic nanohybrid scaffold underneath, created a tissue analogue of the upper respiratory tract, validating these 3D printed guided scaffolds as a platform to support co-culture and cellular organization. In particular, hBM-MSCs in the co-culture system promoted an overall matured physiological tissue analogue of the respiratory system, a promising synthetic tissue for drug discovery, tracheal repair and reconstruction. Statement of significance Respiratory diseases are a common medical condition and represent a leading cause of death in the world. However, the epithelium is one of the most challenging tissues to culture in vitro, and suitable tracheobronchial models, physiologically representative of the innate airway, remain largely elusive. This study presents, for the first time, a systematic approach for the development of functional multilayered epithelial synthetic tissue in vitro via co-culture on a 3D-printed thermoresponsive elastomer interpenetrated with a collagen hydrogel network. The viscoelastic nature of the scaffold with stiffness softening at body temperature provide a promising matrix for soft tissue engineering. The results presented here provide new insights about the epithelium at different surfaces and interfaces of co-culture, and pave the way to offer a customizable reproducible technology to generate physiologically relevant 3D biomimetic systems to advance our understanding of airway tissue regeneration

The interaction of metal oxide surfaces with complexing agents dissolved in water

Upon exposure to liquid water or to aqueous solutions, the surfaces of metal oxide particles or films undergo a series of chemical reactions that are dictated to a large extent by the chemistry of the metal ions involved. These reactions involve surface hydroxylation and hydration (dissociative and non-dissociative water chemisorption), chemisorption of solutes and charge transfer reactions. The present review focuses on the chemisorption of anions, which is a surface complexation reaction. In simple cases, chemical equilibria may be written, and quantified by heterogeneous stability constants that resemble the analogous homogeneous ones. This approach has been practiced for more than 20 years, and in selected cases values are available for a discussion of stability trends, even though the stability constant values are sensitive to double-layer modeling and to the history of the metal oxide used. Most of the stability constants have been derived in conventional ways from measurements of the corresponding adsorption isotherms, a procedure that does not provide structural information. Modeling of the shape and pH dependence of adsorption isotherms has been however used to propose various modes of adsorption, in order to derive, for instance, the speciation of surface complexes as a function of ligand concentration and pH. Presently, structural techniques are available to probe directly into the structure of the surface ensembles; the use of UV-vis, IR, magnetic and surface spectroscopies, together with EXAFS and SEXAFS has provided credence to the surface complexation approach, as discussed in the present review for selected cases. In particular, attenuated total refection FTIR has proved to be a powerful tool to derive the surface speciation in selected cases. The reactivity patterns of the surface complexes is being currently explored. The catalysis of ester hydrolysis, the rates and mechanisms of oxide dissolution, heterogeneous charge transfer reactions and the photocatalytic reactions of oxidation of organic compounds can all, in certain cases, be described as reactions of specific surface complexes; some relevant examples are discussed.Fil: Blesa, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Weisz, Ariel D.. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Morando, Pedro Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Salfity, José Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Magaz, María del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Regazzoni, Alberto Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentin

Porous, aligned and biomimetic fibers of regenerated silk fibroin produced by solution blow spinning

Solution blow spinning (SBS) has emerged as a rapid and scalable technique for the production of polymeric and ceramic materials into micro-/nanofibers. Here, SBS was employed to produce submicrometer fibers of regenerated silk fibroin (RSF) from <i>Bombyx mori</i> (silkworm) cocoons based on formic acid or aqueous systems. Spinning in the presence of vapor permitted the production of fibers from aqueous solutions, and high alignment could be obtained by modifying the SBS setup to give a concentrated channeled airflow. The combination of SBS and a thermally induced phase separation technique (TIPS) resulted in the production of macro-/microporous fibers with 3D interconnected pores. Furthermore, a coaxial SBS system enabled a pH gradient and kosmotropic salts to be applied at the point of fiber formation, mimicking some of the aspects of the natural spinning process, fostering fiber formation by self-assembly of the spinning dope. This scalable and fast production of various types of silk-based fibrous scaffolds could be suitable for a myriad of biomedical applications

Occurrence, associated factors and soft tissue reconstructive therapy for buccal soft tissue dehiscence at dental implants: Consensus report of group 3 of the DGI/SEPA/Osteology Workshop.

OBJECTIVES To systematically assess the literature and report on (1) the frequency of occurrence of buccal soft tissue dehiscence (BSTD) at implants, (2) factors associated with the occurrence of BSTD and (3) treatment outcomes of reconstructive therapy for the coverage of BSTD. MATERIALS AND METHODS Two systematic reviews addressing focused questions related to implant BSTD occurrence, associated factors and the treatment outcomes of BSTD coverage served as the basis for group discussions and the consensus statements. The main findings of the systematic reviews, consensus statements and implications for clinical practice and for future research were formulated within group 3 and were further discussed and reached final approval within the plenary session. RESULTS Buccally positioned implants were the factor most strongly associated with the risk of occurrence of BSTD, followed by thin tissue phenotype. At immediate implants, it was identified that the use of a connective tissue graft (CTG) may act as a protective factor for BSTD. Coverage of BSTD may be achieved with a combination of a coronally advanced flap (CAF) and a connective tissue graft, with or without prosthesis modification/removal, although feasibility of the procedure depends upon multiple local and patient-related factors. Soft tissue substitutes showed limited BSTD coverage. CONCLUSION Correct three-dimensional (3D) positioning of the implant is of utmost relevance to prevent the occurrence of BSTD. If present, BSTD may be covered by CAF +CTG, however the evidence comes from a low number of observational studies. Therefore, future research is needed for the development of further evidence-based clinical recommendations