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 of technologies to realize these systems. - Knowledge and understanding of gene therapy and its potential in medicine. - Advanced Knowledge of nanotechnology and of micro and nanostructured materials application in biomedicine. 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 solution and new material design in medicine.

- Basic knowledge of cell biology and physiology. - Basic knowledge of general chemistry, organic chemistry, biochemistry, polymerization reactions. - 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 immunoresponse - Diseases with a high social burden and challenging treatment: cancer, cardiovascular and neurodegenerative diseases, osteoporosis 2. ENABLING TECHNOLOGIES FOR CLINICAL CHALLENGES WITH HIGH SOCIAL BURDEN: CANCER AND NEURODEGENERATIVE DISEASES (22.5 hrs) - 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 using organ-on-chip. - Magnetic and magneto-plasmonic nanoparticles for tumor treatment 3. ENABLING TECHNOLOGIES FOR UNSOLVED CLINICAL CHALLENGES: FROM BIOCOMPATIBLE TO MULTIFUNCTIONAL BONE DEVICES (6 hours) - Bone remodeling - Methods to characterize bone tissue and in vitro approaches to evaluate remodeling. - 3D bone-like scaffold enabling multiple stimuli 4. TECHNOLOGIES AND SMART MATERIALS TO FIGHT CHRONIC, INFECTED WOUNDS, DELAYED BONE HEALING, OSTEOPOROSIS (3 hours) - Smart multifunctional materials releasing ion and biomolecules upon a specific stimulus - Surface functionalization of materials and 3D scaffolds to impart anti-osteoclastogenic properties 5. MULTIFUNCTIONAL MATERIALS FOR CANCER TREATMENT (9 hours) - Magnetic biomaterials to treat pathological bone tissue: multifunctional materials from the macro to the nanoscale - Magnetic and magneto-plasmonic nanoparticles for theranostics 6. LAYER-BY-LAYER ASSEMBLY TO SURFACE FUCNTIONALISE MEDICAL DEVICE AT THE NANOSCALE (9 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 (flipped classroom) is planned (also delivered either in the classroom or in the virtual classroom) in which the most recent approaches for the development of 3D in vitro models of some specific, healthy and pathological tissues are discussed through some applicative examples. The exercise involves a brief (optional) teamwork to evaluate the learning of the illustrated and the skills through the re-elaboration and critical analysis of the state of the art, which the students will produce in teamwork performed in small groups. This activity, if carried out by the student, is assessed with a score up to 2/30 that will contribute to the final exam mark. Other similar exercises might be carried out for other course topics but with no scoring associated.

Slides ,tutorials and literature references provided by the teachers and available through the website. Since the course targets 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 example of up-to-date references for reading are: [1] S. F. Boj et al., “Organoid models of human and mouse ductal pancreatic cancer,” Cell, vol. 160, no. 1–2, pp. 324–338, Jan. 2015, doi: 10.1016/j.cell.2014.12.021. [2] G. Lazzari, V. Nicolas, M. Matsusaki, M. Akashi, P. Couvreur, and S. Mura, “Multicellular spheroid based on a triple co-culture: A novel 3D model to mimic pancreatic tumor complexity,” Acta Biomater., vol. 78, pp. 296–307, Sep. 2018, doi: 10.1016/j.actbio.2018.08.008. [3] Y. Shichi et al., “Enhanced morphological and functional differences of pancreatic cancer with epithelial or mesenchymal characteristics in 3D culture,” Sci. Rep., vol. 9, no. 1, p. 10871, Dec. 2019, doi: 10.1038/s41598-019-47416-w. [4] S. Totti, M. C. Allenby, S. B. Dos Santos, A. Mantalaris, and E. G. Velliou, “A 3D bioinspired highly porous polymeric scaffolding system for: In vitro simulation of pancreatic ductal adenocarcinoma,” RSC Adv., vol. 8, no. 37, pp. 20928–20940, 2018, doi: 10.1039/c8ra02633e. [5] P. Gupta, P. A. Pérez-Mancera, H. Kocher, A. Nisbet, G. Schettino, and E. G. Velliou, “A Novel Scaffold-Based Hybrid Multicellular Model for Pancreatic Ductal Adenocarcinoma—Toward a Better Mimicry of the in vivo Tumor Microenvironment,” Front. Bioeng. Biotechnol., vol. 8, no. April, 2020, doi: 10.3389/fbioe.2020.00290. [6] B. F. L. Lai et al., “Recapitulating Pancreatic Tumor Microenvironment through Synergistic Use of Patient Organoids and Organ-on-a-Chip Vasculature,” Adv. Funct. Mater., vol. 2000545, pp. 1–16, 2020, doi: 10.1002/adfm.202000545.

Exam: Compulsory oral exam;

The final exam will consist in a critical discussion of scientific text(s) (paper, review, book chapter) strictly related to the course topics. The suggested combination is a more general text introducing the state-of-the-art of the selected subject (e.g. a review paper or a book chapter) and 1, max. 2 papers describing a case study. The texts have to be agreed with the teacher(s) and will be summarized and analysed in a public seminar (typically delivered with a slide presentation) by a single student (for max 10’) or groups of 2-3 students (for max. 20’-30’), delivered in presence complying with the safety rules in force. The presentation will be followed by a discussion (with questions addressed to each student) that, inspired by what is presented in the seminar, will cover the course topics. Overall duration of the exam will be 20’ and 40’-60’ for the single student and groups of 2-3 students, respectively. 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 slides prepared for the presentation. The grading of the exam will be implemented as follows: - Content of the presentation: up to 10 points - Quality of the presentation delivered: up to 10 points - Answers to questions: up to 10 points - Flipped Classroom bonus (optional): up to 2 points. All marks will be typically the average of the marks given by at least two different teachers. In order to pass the exam a minimum of 6 out of 10 points are needed in the “answer to questions” part. If at least 30 points are reached in this way the board of examiner might propose the "cum laude" if there is unanimity.

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.