Guided Tissue Regeneration in Heart Valve Replacement: From Preclinical Research to First-in-Human Trials

Heart valve tissue-guided regeneration aims to offer a functional and viable alternative to current prosthetic replacements. Not requiring previous cell seeding and conditioning in bioreactors, such exceptional tissue engineering approach is a very fascinating translational regenerative strategy. After in vivo implantation, decellularized heart valve scaffolds drive their same repopulation by recipient’s cells for a prospective autologous-like tissue reconstruction, remodeling, and adaptation to the somatic growth of the patient. With such a viability, tissue-guided regenerated conduits can be delivered as off-the-shelf biodevices and possess all the potentialities for a long-lasting resolution of the dramatic inconvenience of heart valve diseases, both in children and in the elderly. A review on preclinical and clinical investigations of this therapeutic concept is provided with evaluation of the issues still to be well deliberated for an effective and safe in-human application

Cutting-Edge Regenerative Medicine Technologies for the Treatment of Heart Valve Calcification

http://Laura Iop and Gino Gerosa (2013). Cutting-Edge Regenerative Medicine Technologies for the Treatment of Heart Valve Calcification, Calcific Aortic Valve Disease, Dr. Elena Aikawa (Ed.), ISBN: 978-953-51-1150-4, InTech, DOI: 10.5772/55327. Available from: http://www.intechopen.com/books/calcific-aortic-valve-disease/cutting-edge-regenerative-medicine-technologies-for-the-treatment-of-heart-valve-calcificatio

DESIGN AND PROTOTYPING OF A FLEXIBLE PREFABRICATED MODULE FOR LOFT CONVERSIONS. THE “MADE IN ITALY” NATIONAL RESEARCH PROGRAMME.

In order to cope with the modern environmental, economic and social issues, urban densification appears as one of the possible solutions to limit land consumption, infrastructure and transport costs, to increase quality of life and to promote a more efficient use of energy in metropolitan areas. Since ancient times the addition of new volumes to the existing building has been adopted as an ordinary practice to respond to the changing needs of the inhabitants. Today rooftop architecture can be used to intensify the existing metropolitan areas, inject them with new vitality and diversify the mono-functionality of a neighbourhood. Besides, it represents an opportunity for the energy upgrading of the built environment since the exploitation of rooftop space as open available area where to erect new structures not only allows for land consumption control but also it often entails the requalification of the roofing construction. Moreover the addition of new inhabitable spaces can be part of a governmental or municipal energy incentive policy to trigger private initiatives towards refurbishment and requalification projects aimed at improving the overall energy efficiency of the ‘supporting’ existing buildings. This paper describes the results of an ongoing multidisciplinary government funded research project focusing on the development and prototyping of an energy efficient flexible and adaptable modular prefabricated system for residential rooftop additions exploiting Xlam laminated timber panels. In particular this work presents the meta-design concept of the prefabricated system as the final outcome of a specific methodological process which through preliminary targets definition, users requirements assessment and the exploration and evaluation of different techno-typological solutions has been conceived in order to provide the maximum adaptability and spatial and combination flexibility as well as the highest energy efficiency (passive and active systems) to the modules

Multiphoton Label-Free ex-vivo imaging using a custom-built dual-wavelength microscope with chromatic aberrations compensation

Label-Free Multiphoton Microscopy is a very powerful optical microscopy that can be applied to study samples with no need for exogenous fluorescent probes, keeping the main benefits of a Multiphoton approach, like longer penetration depths and intrinsic optical sectioning, while opening the possibility of serial examinations with different kinds of techniques. Among the many variations of Label-Free MPM, Higher Harmonic Generation (HHG) is one of the most intriguing due to its generally low photo-toxicity, which enables the examination of specimens particularly susceptible to photo-damages. HHG and common Two-Photon Microscopy (TPM) are well-established techniques, routinely used in several research fields. However, they require a significant amount of fine-tuning in order to be fully exploited and, usually, the optimized conditions greatly differ, making them quite difficult to perform in parallel without any compromise on the extractable information. Here we present our custom-built Multiphoton microscope capable of performing simultaneously TPM and HHG without any kind of compromise on the results thanks to two, separate, individually optimized laser sources with full chromatic aberration compensation. We also apply our setup to the examination of a plethora of ex vivo samples in order to prove the significant advantages of our approach

Transapical off-pump mitral valve repair with Neochord Implantation (TOP-MINI): step-by-step guide

open10openColli, Andrea; Zucchetta, Fabio; Torregrossa, Gianluca; Manzan, Erica; Bizzotto, Eleonora; Besola, Laura; Bellu, Roberto; Sarais, Cristiano; Pittarello, Demetrio; Gerosa, GinoColli, Andrea; Zucchetta, Fabio; Torregrossa, Gianluca; Manzan, Erica; Bizzotto, Eleonora; Besola, Laura; Bellu, Roberto; Sarais, Cristiano; Pittarello, Demetrio; Gerosa, Gin

The light and shadow of senescence and inflammation in cardiovascular pathology and regenerative medicine

Recent epidemiologic studies evidence a dramatic increase of cardiovascular diseases, especially associated with the aging of the world population. During aging, the progressive impairment of the cardiovascular functions results from the compromised tissue abilities to protect the heart against stress. At the molecular level, in fact, a gradual weakening of the cellular processes regulating cardiovascular homeostasis occurs in aging cells. Atherosclerosis and heart failure are particularly correlated with aging-related cardiovascular senescence, that is, the inability of cells to progress in the mitotic program until completion of cytokinesis. In this review, we explore the intrinsic and extrinsic causes of cellular senescence and their role in the onset of these cardiovascular pathologies. Additionally, we dissect the effects of aging on the cardiac endogenous and exogenous reservoirs of stem cells. Finally, we offer an overview on the strategies of regenerative medicine that have been advanced in the quest for heart rejuvenation

biocompatibility issues of next generation decellularized bioprosthetic devices

With respect to the limited lifespan of glutaraldehyde-treated bioprostheses (BHVs) to date there is almost no alternative when heart valve replacement surgery is required and most advanced current research attempts to develop tissue engineered valve scaffolds to be implantedin vivoor afterin vitropreconditioning and dynamic seeding with host cells. However the clinical outcomes of grafting detergent-based cell-depleted tissue engineered xenogeneic constructs are still controversial. Insufficient quantitative evaluations performed at preclinical level about the residual content of xenogeneic epitopes, detergents, and nucleic acid materials in such scaffolds have led to disappointing and disastrous results. The risk of these dramatic accidents reoccurring remains very high unless safety and reliable control tools aimed to reach their complete removal, in order to consider tissues biocompatible and suitable for clinical practice

The Rapidly Evolving Concept of Whole Heart Engineering

Whole heart engineering represents an incredible journey with as final destination the challenging aim to solve end-stage cardiac failure with a biocompatible and living organ equivalent. Its evolution started in 2008 with rodent organs and is nowadays moving closer to clinical application thanks to scaling-up strategies to human hearts. This review will offer a comprehensive examination on the important stages to be reached for the bioengineering of the whole heart, by describing the approaches of organ decellularization, repopulation, and maturation so far applied and the novel technologies of potential interest. In addition, it will carefully address important demands that still need to be satisfied in order to move to a real clinical translation of the whole bioengineering heart concept

Nanopatterned acellular valve conduits drive the commitment of blood-derived multipotent cells

Considerable progress has been made in recent years toward elucidating the correlation among nanoscale topography, mechanical properties, and biological behavior of cardiac valve substitutes. Porcine TriCol scaffolds are promising valve tissue engineering matrices with demonstrated self-repopulation potentiality. In order to define an in vitro model for investigating the influence of extracellular matrix signaling on the growth pattern of colonizing blood-derived cells, we cultured circulating multipotent cells (CMC) on acellular aortic (AVL) and pulmonary (PVL) valve conduits prepared with TriCol method and under no-flow condition. Isolated by our group from Vietnamese pigs before heart valve prosthetic implantation, porcine CMC revealed high proliferative abilities, three-lineage differentiative potential, and distinct hematopoietic/endothelial and mesenchymal properties. Their interaction with valve extracellular matrix nanostructures boosted differential messenger RNA expression pattern and morphologic features on AVL compared to PVL, while promoting on both matrices the commitment to valvular and endothelial cell-like phenotypes. Based on their origin from peripheral blood, porcine CMC are hypothesized in vivo to exert a pivotal role to homeostatically replenish valve cells and contribute to hetero- or allograft colonization. Furthermore, due to their high responsivity to extracellular matrix nanostructure signaling, porcine CMC could be useful for a preliminary evaluation of heart valve prosthetic functionality

Seasonal variation of size-resolved aerosol fluxes in a Peri-urban deciduous broadleaved forest

Eddy covariance measurements of aerosol fluxes were performed above an oak-hornbeam forest in the Po Plain (Northern Italy), from February to May and from September to December 2019. Measurements aimed at assessing the influence of forest phenology and leaf presence/absence on the seasonal evolution of size-segregated aerosol fluxes. The size-resolved aerosol concentration in the range 0.006-10 μm was sampled with a 14-stage impactor (ELPI+, Dekati, FI), and the filters exposed in May were subjected to chemical analysis. Over the whole sampling period, the forest removed from the atmosphere an average of 3.12 mg of aerosol m−2 d−1. The direction and the intensity of the aerosol fluxes were not constant through the year, as a strong seasonal and size-dependent variability emerged. In particular, leaf-presence drove a net deposition of the accumulation mode aerosol (100 nm< particle diameter Dp<1000 nm) and an emission of the Aitken (10 nm< Dp<100 nm) and coarse mode (Dp>1000 nm) aerosols. On the contrary, in absence of leaves all the sub-micrometer aerosol size-classes showed net daily upward fluxes, while coarse mode aerosol fluxes were prevalently downward. Monthly averages of deposition velocities of Aitken and accumulation mode aerosols correlated with the Leaf Area Index (LAI) seasonal trend, thus indicating an important role of the amount of the leaf surface area on the deposition and emission of these size-classes. Furthermore, an influence of the stomatic activity was suggested for the Aitken mode aerosol, since its deposition velocity followed the same diel course of the stomatal conductance to water. The analysis of the influence of meteorological parameters on aerosol deposition velocities highlighted that dynamic and convective turbulence (described by friction velocity, u* and Deardorff velocity, w*) enhanced the vertical aerosol exchanges, both upward and downward, while the approaching of condensing conditions reduced the flux intensities