At the end of the module, the student will have acquired the knowledge of the enabling technologies in the design of advanced tools treating challenging diseases. In detail, the student will have acquired: 1) KNOWLEDGE AND UNDERSTANDING - Knowledge of advanced cell biology, physiology and pathophysiology for a better understanding of the mechanisms underlying high-impact diseases. - General knowledge of physiological and pathological in vitro models and technologies (biomaterials, scaffolds, microfluidics, biological components) to realize/miniaturize these systems. - Advanced Knowledge of nanotechnology and micro- and nano- structured materials and bioinks application in biomedicine. - Knowledge of the state-of-the-art concerning in vitro organ models developed at higher (>3) TRL (technology readiness level) - Basic knowledge of the regulatory, technological and economic barriers/requirements for in vitro organ models implementation 2) CAPABILITY TO APPLY KNOWLEDGE AND UNDERSTANDING - Application of the acquired knowledge of advanced cell biology, physiology and pathophysiology to inform the design of proper bioengineered systems for disease modeling and treatment testing. - Skills in the development of highly technological approaches to treat challenging diseases. - Skills in the design of biomimetic or bioinspired systems to reproduce human complexity. - Application of the acquired knowledge to engineer new solutions and new material design in medicine. - Skills in bottom-up design and engineering of in vitro tissue and organ models, with special focus on microfluidic systems.

- Basic knowledge of cell biology and physiology. - Basic knowledge of general chemistry, organic chemistry, biochemistry, macromolecular chemistry, materials technology with a special focus on polymers. - Knowledge of biomaterials and bionanotechnology.

1. ADVANCED BIOLOGICAL BACKGROUND (4.5 hours of lessons, 3 hours of exercises) - Internal physiological barriers in the human body: a special focus on endothelial and blood brain barriers - Diseases with a high social burden and challenging treatment: cancer, cardiovascular and neurodegenerative diseases. - Organ-on-chip cellularisation: which type of cells, why and how? - Matching disease with the right type of organ-on-chip platform. 2. ENABLING TECHNOLOGIES TO UNDERSTAND AND DEAL WITH CLINICAL CHALLENGES WITH A HIGH SOCIAL BURDEN (13.5 hours of lessons, 39 hours of exercises) - In vitro models as advanced strategies to study physiology and pathology and to test the efficacy of novel drugs, the safety of devices, the toxicity of chemicals. Bioinks as enabling materials for organ modelling. - Mimicking human complexity and diseases through in vitro tissue, organ and tumor models (on-chip, based on tissue engineering techniques), patient avatars in zebrafish. - Examples of high TRL devices for tissue and organ models. - Basics of selection/design of components of tissue models on chip. 24 hours of tutorials will be offered, during exercise hours or on demand after booking, for all the students needing specific support in the preparation of the exam.

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The teaching will be delivered in the classroom (or in the virtual classroom if necessary) in a common modality, which will consist of a series of lectures and active practical exercises (such as but not limited to illustration of case studies). The course is structured in 60 hours, of which 18 hours of lessons and 42 hours of exercises. In particular, an interactive practice is planned, consisting in teamwork where groups of students will develop real case studies aimed at the design of an in vitro, innovative and bio-engineered system that could be transferred to the current biomedical market. More specifically, students will apply the knowledge acquired during the course to sketch a project for a tissue/organ on chip device. The activity will be performed in small groups and will be carried out in the classroom under the guidance of at least one teacher. This work will be completed within the duration of the course, and the final report will be due 5 days after the end of the course at the latest. The activity will be assessed with a score up to 9/30 that will add to the final exam mark for students who will present the completed project. Tutoring activities will be offered to support the preparation of the projects. Moreover, during the last week of the course, the tutor will conduct, on request of the students, a preliminary evaluation of the completed work, by assigning a score (max. 1 point) that will contribute to the final grade. Interactive Q&A sessions are also planned (usually at the end of the lesson) to verify the knowledge of the course topics.

Slides and literature references provided by the teachers and available through the website. “Molecular Biology of the Cell” Bruce Alberts, et al., New York: Garland Science; 2002. ISBN-10: 0-8153-3218-1ISBN-10: 0-8153-4072-9 is suggested as the classic in-depth text reference to recall the fundamentals in cell biology. Since the course targets advanced cell biology concepts, the innovative aspects of bionanotechnology and their application in medicine, there is no suitable textbook of reference. However, updated literature material will be indicated to the students for each specific topic. Some examples of up-to-date references for reading are: ... [1] Ingber, D.E. Human organs-on-chips for disease modelling, drug development and personalized medicine. Nat Rev Genet 23, 467–491 (2022). https://doi.org/10.1038/s41576-022-00466-9 [2] Marie Weinhart, Andreas Hocke, Stefan Hippenstiel, Jens Kurreck, Sarah Hedtrich 3D organ models—Revolution in pharmacological research? Pharmacological Research Volume 139, January 2019, Pages 446-451 https://doi.org/10.1016/j.phrs.2018.11.002 [3] Jin, Z., Li, Y., Yu, K., Liu, L., Fu, J., Yao, X., Zhang, A., He, Y., 3D Printing of Physical Organ Models: Recent Developments and Challenges. Adv. Sci. 2021, 8, 2101394. https://doi.org/10.1002/advs.202101394 [4] D. Hill et al. “A Novel Fully Humanized 3D Skin Equivalent to Model Early Melanoma Invasion” Molecular cancer Therapeutics 14(11) 2015 https://doi.org/10.1158/1535-7163.MCT-15-0394 [5] M. Fazio et al. “Zebrafish patient avatars in cancer biology and precision cancer therapy” Nature reviews Cancer 20 2020 https://doi.org/10.1038/s41568-020-0252-3

Lecture slides; Text book;

Exam: Compulsory oral exam;

The final exam will consist of the illustration (through slides, movies, animations, or other visual means) of the completed device designed during practical activity in the classroom. Each team will have a maximum of 15’ to present the whole project. The presentation will be followed by a discussion (with questions addressed to each student) that will cover details of the project, for approx. additional 5’ per student. The overall exam aims to assess the following: 1. knowledge level and understanding capability acquired by the student on - advanced cell biology, physiology and pathophysiology for a better understanding of the mechanisms underlying high-impact diseases - in vitro models and technologies to realize these systems - nanotechnology and micro and nanostructured materials application in biomedicine 2. the acquired capability to apply knowledge and understanding considering - application of the acquired knowledge of advanced cell biology, physiology and pathophysiology to inform the design of proper bioengineered systems for disease modeling and treatment testing. - skills in the development of highly technological approaches to treat challenging diseases - skills in the design of biomimetic or bioinspired systems to reproduce human complexity - application of the acquired knowledge to engineer new solution and new material design in medicine. During the exam, it will not be possible to consult tests, lecture materials, and notes, with except for the visual support prepared for the project presentation, if any. The grading of the exam will be implemented as follows: - Practical activity report: up to 10 points (9 points if no pre-evaluation is carried out) - Project presentation: up to 10 points - Answers to questions/discussion: up to 10 points The maximum grade will, therefore, be 30/30. For students reaching this maximum grade, the board of examiners, in the presence of elements of excellence, may award the student with a “cum laude” evaluation.

In addition to the message sent by the online system, students with disabilities or Specific Learning Disorders (SLD) are invited to directly inform the professor in charge of the course about the special arrangements for the exam that have been agreed with the Special Needs Unit. The professor has to be informed at least one week before the beginning of the examination session in order to provide students with the most suitable arrangements for each specific type of exam.