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, scaffolds, microfluidics, biological components) to realize/miniaturize these systems. - Knowledge and understanding of gene therapy and its potential in medicine. - 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) - Knowledge of the regulatory, technological and economic barriers/requirements for in vitro organ models implementation 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.

N.B. during the course, students will have to select one of the two different tracks offered (Track A: device; Track B: research. See details below for the specific features of each track.) 1. THE BIOLOGICAL BACKGROUND (10.5 hours) - Recalls of basic concepts of cell biology and physiology - Stem cells and their potential in medicine - Barriers in the human body: a special focus on endothelial and blood brain barriers - The immune response - Diseases with a high social burden and challenging treatment: cancer, cardiovascular and neurodegenerative diseases, osteoporosis 2. ENABLING TECHNOLOGIES TO UNDERSTAND AND DEAL WITH CLINICAL CHALLENGES WITH A HIGH SOCIAL BURDEN (24 hours of lessons, 7,5 hours exercise for Track B, 21 hours for track A) - 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. - New genetic and stem cell therapy techniques to treat challenging diseases - Mimicking the human complexity and diseases through in vitro tissue, organ and tumor models (on-chip, based on tissue engineering techniques), patient avatars in zebrafish. - Research frontiers in Biomimetics. - Examples of high TRL devices for tissue and organ models. - Basics of selection/design of components of tissue models on chip (Track A only). 3. ENABLING TECHNOLOGIES FOR UNSOLVED CLINICAL CHALLENGES: FROM BIOCOMPATIBLE TO MULTIFUNCTIONAL DEVICES (1, 5 hours for track A 6 hours for track B) - Scaffold and surface modifications enabling multiple stimuli - Carriers and strategies to release ions and drugs for several applications (wound healing, treatment of ocular disease, cardiac and colorectal applications) 4. 1. MULTIFUNCTIONAL MATERIALS FOR MODULATION OF THE INFLAMMATORY RESPONSE (1, 5 hours for track A, 6 hours for track B) - Foreign body and inflammatory response: strategies to modulate inflammation by targeting the different biological stages of the host response (Focus on therapeutic and engineering approaches to control material–immune system interactions.) - Biomaterial surface properties influencing inflammation and foreign body response: examples of natural or synthetic materials with pro- or anti-inflammatory characteristics. (Exploration of how material composition and surface features affect immune activation.) 5. LAYER-BY-LAYER ASSEMBLY TO SURFACE FUNCTIONALISE MEDICAL DEVICE AT THE NANOSCALE (1,5 hours for track A 6 hours for track B) - Definition of the Layer-by-Layer assembly and processing parameters for its execution - Applications of Layer-by-Layer assembly in Bone Regeneration and Drug Delivery Systems 15 hrs 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.

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 practical exercises (e.g., illustration of case studies). The course is structured in 60 hours, of which 42 hours are provided to all the students, while the remaining 18 hours are differentiated for two groups of students, belonging to Track A and B (see the section “Course Topics”). For group A, 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. In particular, 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 latest. The activity will be assessed with a score up to 10/30 that will add to the final exam mark for students who will present the completed project. For group B, students will prepare (individually), a draft of a research project proposal, as an exercise,. The presentation and discussion of this research draft during the exam will contribute to the final exam mark with a score (score up to 15/30). For both tracks, tutoring activities will be offered to support the preparation of the projects and research proposals. 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. An interactive Q&A session is also planned to verify the knowledge of the course topics for both tracks.

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 [6] S. Capuani, G. Malgir, C. Ying Xuan Chua, A. Grattoni, Advanced strategies to thwart foreign body response to implantable devices. Bioeng Transl Med. 2022;e10300 https://doi.org/10.1002/btm2.10300 [7] X. Li, et al., Magnetic nanoparticles for cancer theranostics: Advances and prospects, Journal of Controlled Release, 335, 2021, 437-448, https://doi.org/10.1016/j.jconrel.2021.05.042 [8] J. Kadkhoda et al., Recent advances and trends in nanoparticles based photothermal and photodynamic therapy, Photodiagnosis and Photodynamic Therapy, 37, 2022. https://doi.org/10.1016/j.pdpdt.2021.102697.

Lecture slides;

Exam: Compulsory oral exam;

Compulsory oral exam; Compulsory oral exam; For students of the group A, the final exam will consist in the illustration (through slides, movies, animations or other visual means) of the completed device designed during the 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 additional approx. 5’ per student. For students of the group B, the final exam will consist in the presentation and discussion of the draft of a research project proposal prepared during the practical activity in the classroom and related to the topics covered by the teacher of preference (approx. 15’ per student). A discussion on course topics with Q&A will follow (5’) The overall exam aims to assess the following: 1. knowledge level and understanding capability acquired by the student on - advanced cell biology and physiology for a better understanding of the mechanisms underlying high-impact diseases - in vitro models and technologies to realize these systems - gene therapy and its potential in medicine - nanotechnology and micro and nanostructured materials application in biomedicine 2. the acquired capability to apply knowledge and understanding considering - 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 material and notes, with the exception of the visual support prepared for the project’s presentation, if any. The grading of the exam will be implemented as follows: Students of track A, - Practical activity report: up to 11 points (10 points if no pre-evaluation is carried out) - Project presentation: up to 11 points - Answers to questions/discussion: up to 11 points Students of the group B, who did not attend the practical activity - presentation and discussion of the draft of the research project proposal: up to 16 points. (15 points if no pre-evaluation is carried out) - Answers to questions on course topics: up to 16 points

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.