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Tissue bioengineering: evaluate skin xenograft using porcine acellular matrices and effect of annexin A1 protein as a therapeutic approach in the regenerative and wound healing processes

Abstract

The loss of skin and appendages from non-healing wounds or surgical complications, excision of complicated hernias, cancer or severe burns have created great expectations for new technologies in the field of tissue engineering. The advances in this area have led to the development of several products (synthetic and biological) for using in transplants and aiming to improve patients' quality of life through the restoration, maintenance and function of transplanted tissues and organs. Designed as skin substitutes, equivalents of the epidermis and dermis have been investigated and used clinically for several years. However, acellular biological materials that are immunologically compatible and suited for the repair of skin, either as a fill (dermis) or support and protection (epidermis), must be carefully implemented. Thus, our objective will be to standardize an economically viable technique of skin decellularization, for the development of acellular scaffolds and a method to characterize them biochemically, biomechanically and structurally. To evaluate the biocompatibility of the scaffolds we will first experiment with subcutaneous implantation of scaffolds in rats. In a second experiment, we will perform the transplantation of scaffolds, with or without the treatment with the annexin A1 (AnxA1) protein and the immunosuppressant, cyclosporin. The following aspects will also be evaluated: 1) the biocompatibility of implants / transplants to the host tissue (healing process, integration of the implant, host cell density in implant, presence of mast cells and mineralization of subcutaneous implantation); 2) AnxA1 protein expression in leukocytes located in heterografts; 3) the process of apoptosis and neovascularization by AnxA5 expression and Von Willebrand factor, respectively; 4) the regenerative potential of the scaffolds and immunogenic response in different experimental conditions by means of phenotypic macrophage M1/M2, and gene expression of growth factors FGF and TGF; 5) the amount of circulating leukocytes in peripheral blood, and the levels, of proinflammatory cytokines by biochemical analysis. The AnxA1 will be evaluated as a potential therapeutic option to reduce inflammation, to improve healing and the regenerative process of the heterograft, possibly with fewer side effects when compared to traditional therapy. (AU)

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Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
LACERDA, JESSICA ZANI; DREWES, CARINE CRISTIANE; OLIVEIRA MIMURA, KALLYNE KIOKO; ZANON, CAROLINE DE FREITAS; ANSARI, TAHERA; GIL, CRISTIANE DAMAS; GRECO, KARIN VICENTE; POLISELLI FARSKY, SANDRA HELENA; OLIANI, SONIA MARIA. Annexin A1(2-26) Treatment Improves Skin Heterologous Transplantation by Modulating Inflammation and Angiogenesis Processes. FRONTIERS IN PHARMACOLOGY, v. 9, SEP 10 2018. Web of Science Citations: 1.
COSTA, MAURICIO B.; MIMURA, KALLYNE K. O.; FREITAS, ALINE A.; HUNGRIA, EMERITH M.; SOUSA, ANA LUCIA O. M.; OLIANI, SONIA M.; STEFANI, MARIANE M. A. Mast cell heterogeneity and anti-inflammatory annexin A1 expression in leprosy skin lesions. Microbial Pathogenesis, v. 118, p. 277-284, MAY 2018. Web of Science Citations: 0.
TORRES, LIDIANE S.; OKUMURA, JESSIKA V.; SILVA, DANILO G. H.; MIMURA, KALLYNE K. O.; BELINI-JUNIOR, EDIS; OLIVEIRA, RENAN G.; LOBO, CLARISSE L. C.; OLIANI, SONIA M.; BONINI-DOMINGOS, CLAUDIA R. Inflammation in Sickle Cell Disease: Differential and Down-Expressed Plasma Levels of Annexin A1 Protein. PLoS One, v. 11, n. 11 NOV 1 2016. Web of Science Citations: 7.
MIMURA, KALLYNE K. O.; MORAES, ANDREIA R.; MIRANDA, ALINE C.; GRECO, REBECCA; ANSARI, TAHERA; SIBBONS, PAUL; GRECO, KARIN V.; OLIANI, SONIA M. Mechanisms underlying heterologous skin scaffold-mediated tissue remodeling. SCIENTIFIC REPORTS, v. 6, OCT 11 2016. Web of Science Citations: 10.
HEADLAND, SARAH E.; JONES, HEFIN R.; NORLING, LUCY V.; KIM, ANDREW; SOUZA, PATRICIA R.; CORSIERO, ELISA; GIL, CRISTIANE D.; NERVIANI, ALESSANDRA; DELL'ACCIO, FRANCESCO; PITZALIS, COSTANTINO; OLIANI, SONIA M.; JAN, LILY Y.; PERRETTI, MAURO. Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis. Science Translational Medicine, v. 7, n. 315 NOV 25 2015. Web of Science Citations: 77.

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