ABC | Volume 113, Nº1, July 2019

Short Editorial Decellularization of Human Pericardium with Potential Application in Regenerative Medicine Estela de Oliveira Lima, 1 A driana Camargo Ferrasi, 1 Andreas Kaasi 2 Universidade Estadual Paulista Júlio de Mesquita Filho - FMB - Depto. Clínica Médica, 1 Botucatu, SP – Brazil Santa Casa de Misericórdia de São Paulo - Instituto de Pesquisa, Inovação Tecnológica e Educação, 2 São Paulo, SP – Brazil Short Editorial related to the article: Characterization of Decellularized Human Pericardium for Tissue Engineering and Regenerative Medicine Applications Mailing Address: Estela de Oliveira Lima • Universidade Estadual Paulista Júlio de Mesquita Filho - FMB - Departamento de Clínica Médica - Distrito de Rubião Júnior, s/n. Postal Code 18618-687, Botucatu, SP – Brazil E-mail: estela.lima@unesp.br Keywords Regenerative Medicine; Pericardium; Tissue Scaffolds; Cells; Heart Valves/surgery; Translational Medical Research; Biocompatible Materials. DOI: 10.5935/abc.20190130 Regenerative medicine is an interdisciplinary branch of the biomedical sciences that is showing, through the transposition of basic research into the clinic, great potential for therapeutic application, and the field is consequently becoming an important frontman for Translational Medicine. The essence of regenerative medicine consists of the repair or replacement of tissues and organs in which there is structural and functional deficiency. With a view of achieving this objective, several approaches have been proposed, including therapies that include genes, cells, biologic and synthetic scaffolds , which may or may not take part of a tissue engineering strategy. 1 When dealing with synthetic scaffolds, it is possible to manipulate and control structural and mechanical properties, nonetheless, it is not possible to guarantee the same functional capacity as natural tissue. 2 In addition, one of the great challenges is minimizing the risk of immunogenic reactions triggered by the repair scaffold’s composition. 3 Owing to the challenges associatedwith the reestablishment on a functional and structural level of the cell microenvironment, the interest in scaffolds based on natural extracellular matrix (ECM) has increased considerably. With a view of obtaining a biomaterial closely approximating tissues or organs having suffered damage, be it structural or functional, yet at the same time presenting safety from an immunological point of view, a new technology for clinical applications of ECM has been proposed – the decellularization of tissues and organs from human or animal donors. This technology makes use of physical, chemical and/or biochemical methods to eliminate cells from the target tissue/organ, be it xenogeneic or allogeneic, whose antigens represent an elevated risk of immunogenic reaction. The process seeks to ensure immunologic safety and the preservation of basic structural and functional components of the ECM, such as proteins, collagen and glycosaminoglycans (GAGs). The end product is a three-dimensional ECM scaffold with analogous shape to the original tissue, with preserved ultrastructural architecture and with greater biocompatibility and potential of tissue regeneration when compared to synthetic scaffolds. 4 Pericardial tissue, mainly of bovine origin, has been widely used in cardiac surgery, whether for substitution of cardiac valves or for the repair of congenital disorders. Its fibroserous structure, rich in elastic fibres and collagen bundles, bestows upon the pericardium an elevated resistance to mechanical stress, and this resistance, together with the capability of uniform suture retention, represent essential characteristics for application in cardiovascular surgeries. 5,6 With a view of reducing the probability of immunogenic response and rejection of the graft, the pericardium may be submitted to different treatments, among others the tissue fixation using glutaraldehyde, which is routinely used. While this method leads to lower immunogenicity of the tissue, the cytotoxicity and propensity of calcifications are two important inconveniences associated with this technique. 7,8 Faced with these problems, other methods are being developed to improve on the safe utilization of pericardium in cardiac surgery, including decellularization. One of the most established techniques for this purpose is the treatment of the tissue using ionic detergents, such as sodium dodecyl sulfate (SDS). Whereas this decellularization agent is capable of removing undesirable natural components, such as antigenic molecules, it may also lead to structural alterations in the pericardial ECM; the loss of GAGs and important signaling proteins being notable examples. The structural damage caused by the treatment with SDS may impair the ideal in situ or in vitro recellularization of the scaffold, as well as altering the mechanical properties of the matrix, such as elasticity and extensibility. 9 The original work presented by Wollmann et al. 10 in this issue promotes the approach of human pericardium decellularization using a reduced quantity of detergent for application as a cardiovascular patch. The work presents itself with a view of minimizing the impact of the technique and to obtain a human ECM of better quality, non-toxic and that may retain as much as possible the original architecture and composition. The proposed methods exhibit a considerable removal of cell components, including DNA, the presence of which was reduced to approximately one-third of the original content. The tissue was also assessed with respect to cytotoxicity, and it was shown that no cytotoxic effects were seen in vitro . This observation brings a great stimulus for the even deeper investigation of the technique, such as the undertaking of in vivo tests with a view of future clinical application. Moreover, the treatment employed did not alter the composition of the pericardium with respect to the components elastin (qualitative assessment) and collagen (quantitative and qualitative assessment). The treatment did present a significant quantitative reduction in GAGs, which is well known from the literature when the decellularization 18