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 and physiology for a better understanding of the mechanisms underlying high-impact diseases. - General knowledge of physiological and pathological in vitro models and technologies (biomaterials and bioinks, scaffolds, microfluidics, biological components, bioprinting) to realize/miniaturize these systems. - Advanced Knowledge of nanotechnology and micro- and nano- structured materials application in biomedicine. - Knowledge of the state-of-the-art concerning in vitro organ models developed at higher (>3) TRL (technology readiness level) - Knowledge of the regulatory, technological and economic barriers/requirements for in vitro organ models implementation - Acquisition of cross-disciplinary skills (e.g.computer assisted design, data elaboration and analysis) applied to the design of tissue/organ-on-chip. 2) CAPABILITY TO APPLY KNOWLEDGE AND UNDERSTANDING - 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 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 course will be delivered in the classroom (or, if necessary, in a virtual classroom) [VS1.1]through lectures, practical exercises, case studies, and project-based activities. A team-based project will be the core activity of the course. Students will work in small teams on real case studies and apply the knowledge acquired during the course to design an innovative, microfluidics enabled bioengineered tissue/organ-on-chip system with potential applications in biomedical research or the biomedical market. The course is structured to allow students to work on their project from the beginning. Each team will progressively complete specific milestones aimed at increasing the complexity of the proposed device and addressing its biological, scientific, technological, and application requirements. Lectures will generally be delivered to the entire class. For most practical sessions, students will be divided into two groups, and the same activities will be delivered separately to each group. This organization is intended to promote active participation and closer interaction with the instructors. Both groups will follow the same course content, complete the same project milestones, and be assessed according to the same criteria. Within each group, students will work in smaller teams to develop their organ-on-chip projects. Project activities will be carried out under the guidance of the instructors. Tutoring sessions will also be offered throughout the course to support the progressive development of the projects. Two evaluation stages are planned: a preliminary evaluation during the final event and the final examination. 1. At the end of the semester and before the winter break, students can participate in a final event inspired by the “Shark Tank” format[VS2.1]. This is not mandatory. By the date of the final event, each group will be required to submit the final project report and brochure. The submission deadline, required structure, and evaluation criteria for both documents will be communicated to the students during the course. During this pre-evaluation event, each group will present its project as a start-up idea by illustrating a brochure summarizing the clinical need, the proposed device, its innovative features, and its potential applications. Each group will have 5 minutes to present the brochure, followed by a 5-minute discussion with the panel, including two or three questions. All group members are expected to contribute to the presentation or the discussion.[VS3.1] The final event will represent the preliminary evaluation of the project and will contribute up to 2 points to the final grade. The assessment will consider the clarity and effectiveness of the pitch, the quality of the brochure, the consistency and feasibility of the proposed solution, and the students’ ability to answer the panel’s questions and defend their project. 2. During the final examination, each group will present the complete project through a PowerPoint presentation. The presentation will be followed by questions aimed at assessing the students’ knowledge of the course topics, their understanding of the proposed device, and their ability to critically discuss the scientific and technological choices made during the project. The score obtained during the preliminary evaluation will be added to the final examination grade.

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;

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 15min 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 5min 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 final grade will be determined as follows: • Pre-evaluation, not mandatory, during the final “Shark Tank” event, including the presentation of the project brochure and discussion of the submitted project report: up to 2 additional points • Project report and PowerPoint presentation during the final examination: up to 15 points • Answers to questions and discussion during the final examination: up to 15 points N.B. Students who do not participate in the “Shark Tank” event must submit their brochure and report approximately one week before the final examination date. The final examination is graded out of 30 points. The points awarded during the preliminary evaluation are additional and may bring the overall score above 30; however, the maximum final grade recorded will be 30/30. Therefore, only students who participate in the final “Shark Tank” event will be eligible for a “cum laude” evaluation. For eligible students who achieve an overall score above 30 and demonstrate excellence, the board of examiners may award “cum laude.”

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.