At the end of the course, 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 in vitro models and technologies (biomaterials, scaffolds, microfluidics, biological components) to realize these systems. - Knowledge and understanding of gene therapy and its potential in medicine. - Advanced Knowledge of nanotechnology and micro and nanostructured 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 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 on biomaterials and bionanotechnology

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 (31.5 hours) - In vitro models as advanced strategies to study pathologies and test efficacy of novel drugs - 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 3. ENABLING TECHNOLOGIES FOR UNSOLVED CLINICAL CHALLENGES: FROM BIOCOMPATIBLE TO MULTIFUNCTIONAL DEVICES (6 hours) - Bone remodeling - Methods to characterize bone tissue and in vitro approaches to evaluate remodeling - 3D bone-like scaffold enabling multiple stimuli - Carriers to release ions and drugs for several applications (wound healing, treatment of ocular disease, cardiac applications) 4. MULTIFUNCTIONAL MATERIALS FOR MODULATION OF THE INFLAMMATORY RESPONSE (6 hours) - Foreign body and inflammation response: different strategies for modulation of inflammation with an action on the different biological steps of the host response - Biomaterial surface features determining inflammation and foreign body response: examples of natural or synthetic pro- or anti-inflammatory materials 5. LAYER-BY-LAYER ASSEMBLY TO SURFACE FUNCTIONALISE MEDICAL DEVICE AT THE NANOSCALE (6 hours) - Definition of the Layer-by-Layer assembly and processing parameters for its execution - Applications of Layer-by-Layer assembly in Guided Bone Regeneration and Nanotheranostics - Natural-based antibacterial agents as efficient polyelectrolytes to be used in tissue engineering

The teaching will be delivered in the classroom (or in the virtual classroom if necessary) in a common modality, which will consist in a series of lectures and practical exercises (illustration of case studies). An interactive practice is also planned, consisting in a teamwork where students have the possibility to develop a real case study 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 can 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 a teacher. This exercise, if carried out by the student, is assessed with a score up to 9/30 that will contribute to the final exam mark for students who will present the completed project.

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 bionanotechnologies 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

Lecture slides;

Exam: Compulsory oral exam;

The final exam will consist in the illustration (through slides, movies, animations or other visual means) of the completed designed device that was initiated during the practical activity in the classroom (if the student has performed it). Each student will have approx. 10’ to present their part of the project. The presentation will be followed by a discussion (with questions addressed to each student) that will cover details of the project and the course topics addressed (including the underlying biological knowledge), for additional approx. 15’ per student. The contribution to the final mark will be 30% for the project presentation, 40% for the following discussion on the course topics related to the project. The remaining % will be covered by the evaluation of the practical activity. Students that did not take part in the practical activity, will carry out a traditional oral exam (approx. 25’) with questions on the biological basis of the course (contributing to 50% of the mark) and one additional topic among: in vitro tissue and organ models, tumor models, multifunctional devices, multifunctional materials for modulation of the inflammatory response, layer-by-layer assembly to surface functionalize medical devices at the nanoscale (contributing to the remaining 50% of the mark). The 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 who attended the practical activity - Practical activity: up to 9 points - Project presentation: up to 9 points - Answers to questions: up to 12 points Students who did not attend the practical activity - Answers to questions on the biological basis of the course: up to 15 points - Answers to the questions on other topics of the course: up to 15 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.