Ethical Issues in the Use of Animal Models for Tissue Engineering: Reflections on Legal Aspects, Moral Theory, 3Rs Strategies, and Harm-Benefit Analysis Gabriel R. Liguori 1,2* , Bertus F. Jeronimus 3,4* , Tácia T. de Aquinas Liguori 1,2* , Luiz Felipe P. Moreira 2 , Martin C. Harmsen 1 1 Lab for Cardiovascular Regenerative Medicine Research Group (CAVAREM), Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, the Netherlands. 2 Laboratory of Cardiovascular Surgery and Circulation Pathophysiology (LIM-11), Heart Institute (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR 3 University of Groningen, Department of Developmental Psychology, The Netherlands. 4 University of Groningen, University Medical Center Groningen, Department of Psychiatry, Interdisciplinary Center Psychopathology and Emotion regulation (ICPE), The Netherlands. *These authors contributed equally to this work Corresponding Author: Prof.dr. M.C. Harmsen, Dept. Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1 - EA11, 9713 GZ Groningen, the Netherlands. Keywords: Animal Experimentation, Animal Models, Animal Use Alternatives, Morals, Research Ethics, Tissue Engineering, Regulatory Aspects