The course aims to provide knowledge in the context of preclinical testing of biomedical devices. The main aspects of the current legislation on preclinical experimentation will be illustrated, describing the tests needed for the preclinical approval of biomedical devices, with particular reference to animal testing and to alternative methods currently under development, to replace, reduce and refine (Principle of 3R, Replacement, Reduction and Refinement) animal testing. After introducing the current legislation and studying in depth aspects related to the protection of animal welfare, alternative preclinical testing methods currently under development will be illustrated: • in vitro models of organs - organoids • in vitro models of tissues/organs by tissue engineering techniques • in silico models Finally, some successful cases of alternative experimentation will be illustrated. During the course practical exercises will be made.

Knowledge 1) European Standards for preclinical experimentation: in particular the relationship between safety aspects according to ISO 10993-1 and preclinical performance aspects; methods of refinement and reduction in the planning of animal studies. Replacement methods for safety and biocompatibility assessments: potentialities and limitations. The concept of "significant prototype" for research and validation. Sample preparation. Laboratory certifications and GLP methods in preclinical research. 2) Preclinical experimental models in vivo and their integration with those in vitro: i) examples of mouse models of tumor, inflammatory, autoimmune diseases; ii) genome editing - from preclinical to clinical studies; iii) gene therapy. 3) Protection of animal welfare in European legislation: according to the animal species and its normal social organization, environmental factors such as, for example, cage size and its structure, light (intensity, wavelength, photoperiod, frequency), sound, ventilation etc., are as important as the presence or absence of subjects of the same species, their sex and the predictability and controllability of the environment. 4) Statistical elements for a correct evaluation of the number of animal tests required; integration with the ISO 10993-1 regulatory requirements to guarantee the regulatory adequacy of the tests 5) Preclinical experimental models in vitro (organoids, tissue engineering) and their main applications 6) In silico models in preclinical experimentation and their main applications The ability to apply the knowledge and understanding of the topics will be gained through classroom exercises by addressing specific case studies. The purpose will be to: 1) Apply the principles of statistical analysis to animal experimentation 2) Develop / use simple computational models to assist in preclinical testing 3) Analyze experimental approaches to obtain information from in vitro experimental models

1) Basic knowledge of general chemistry, organic chemistry and biochemistry. 2) Basic knowledge of science and technology of inorganic and polymeric materials. 3) Basic knowledge of cell biology and physiology. 4) Basic knowledge of techniques for determining the surface and massive properties of materials. 5) Basic knowledge of statistics 6) Basic knowledge of mechanics of fluids and solids 8) Knowledge on Tissue Engineering

1) European Standards for preclinical experimentation (9 hours) 2) Animal models, principles for the protection of animal welfare in European legislation, examples (12 hours) 3) Statistical elements for a correct evaluation of the needed number of animals during tests, exercises in the classroom and examples (9 hours) 4) Experimental preclinical models (organoids) and their main applications (6 hours) 5) Experimental preclinical models (tissue engineering) and their main applications (9 hours) 6) Computational models in preclinical (and clinical) experimentation and their main applications (15 hours)

• Classroom lessons with slides projection (45 hours) • Classroom exercises (15 hours)

• Slides and articles / material uploaded by the teachers

Modalità di esame: Prova scritta (in aula);

Exam: Written test;

... The exam is written and includes 8 questions (half closed and half open) and has a duration of 1.5 hours. Each question – if perfectly answered – is evaluated 4 points. The exam has the aim to verify the knowledge (with open and closed questions) and the ability to re-elaborate the concepts by the students: in detail, four questions verify the knowledge on the theory; the remaining questions verify the student’s ability to elaborate the concepts learned through verification exercises. It is not possible to consult any text in the examination phase. The exam is passed with a minimum grade of 18. The maximum grade (30L) is awarded with a score greater than or equal to 31. The results of the exam are communicated on the teaching portal, together with the date on which the students can view the exam and ask for clarifications, before registering the mark.

Gli studenti e le studentesse con disabilità o con Disturbi Specifici di Apprendimento (DSA), oltre alla segnalazione tramite procedura informatizzata, sono invitati a comunicare anche direttamente al/la docente titolare dell'insegnamento, con un preavviso non inferiore ad una settimana dall'avvio della sessione d'esame, gli strumenti compensativi concordati con l'Unità Special Needs, al fine di permettere al/la docente la declinazione più idonea in riferimento alla specifica tipologia di esame.