Research Article Biological Niches within Human Calcified Aortic Valves: Towards Understanding of the Pathological Biomineralization Process Valentina Cottignoli, 1 Michela Relucenti, 2 Giovanna Agrosì, 3 Elena Cavarretta, 4 Giuseppe Familiari, 2 Loris Salvador, 5 and Adriana Maras 1 1 Department of Earth Sciences, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy 2 Department of Anatomical, Histological, Legal Medicine and Orthopedics Sciences, Section of Human Anatomy, Electron Microscopy Laboratory “Pietro M. Motta”, Sapienza University of Rome, Via Alfonso Borelli 50, 00161 Rome, Italy 3 Department of Earth and Geoambiental Sciences, Aldo Moro University of Bari, Via Orabona 4, 70125 Bari, Italy 4 Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Corso della Repubblica 79, 04100 Latina, Italy 5 Division of Cardiac Surgery, San Bortolo Hospital, Viale Rodolf 37, 36100 Vicenza, Italy Correspondence should be addressed to Elena Cavarretta; elena.cavarretta@gmail.com Received 19 March 2015; Accepted 7 June 2015 Academic Editor: Umberto Benedetto Copyright © 2015 Valentina Cottignoli et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Despite recent advances, mineralization site, its microarchitecture, and composition in calcifc heart valve remain poorly understood. A multiscale investigation, using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy dispersive X-ray spectrometry (EDS), from micrometre up to nanometre, was conducted on human severely calcifed aortic and mitral valves, to provide new insights into calcifcation process. Our aim was to evaluate the spatial relationship existing between bioapatite crystals, their local growing microenvironment, and the presence of a hierarchical architecture. Here we detected the presence of bioapatite crystals in two diferent mineralization sites that suggest the action of two diferent growth processes: a pathological crystallization process that occurs in biological niches and is ascribed to a purely physicochemical process and a matrix- mediated mineralized process in which the extracellular matrix acts as the template for a site-directed nanocrystals nucleation. Diferent shapes of bioapatite crystallization were observed at micrometer scale in each microenvironment but at the nanoscale level crystals appear to be made up by the same subunits. 1. Introduction Calcifc aortic valve stenosis (CAVS) is an important public health problem and represents the most common form of valvular heart disease in the industrialized countries [1]. It is strictly associated with the formation of ectopic calcifcations within aortic valve leafets that interfere with cusps opening and lead to ventricular outfow obstruction [2] causing important clinical consequences in terms of mortality and morbidity [3]. To date there is no proven medical therapy to halt CAVS course progression, and surgical or percutaneous valve replacement is the only possible treatment of severe CAVS. Te degenerative valve calcifcation process, however, not only is limited to native heart valves but also afects bioprosthetic implants [4]. Despite much efort devoted to unveil the molecular mechanisms leading to valve calcifca- tion, comprehension of the exact process remains uncertain. Chemically, the calcifc deposit within human valve tissue is constituted by a nonstoichiometric apatite, containing high carbonate (CO 3 2− ) content, from 5% to 10% in weight, and AB-type substitutions in apatite lattice [5, 6], as we previously reported; it is ofen indicated as “carbonate apatite” or more Hindawi Publishing Corporation BioMed Research International Volume 2015, Article ID 542687, 10 pages http://dx.doi.org/10.1155/2015/542687