The course aims at providing knowledge in the field of the design of in vitro and in silico models for the preclinical testing of biomedical implants, drugs and
advanced therapies. Innovations in preclinical models - stimulated by EU regulation- will prospect new work opportunities for Biomedical Engineers.
Currently, preclinical investigations on biomedical implants, drugs and advanced therapies proceed through initial in vitro trails, using 2D human cell cultures, followed by in vivo animal tests. However, 2D human cell culture models are not able to closely reproduce cell-cell and cell-extracellular matrix interactions present in human tissues, which indeed possess a 3D complex structure. Animal experiments have greatly contributed to the understanding of the mechanisms of diseases and to the study of new treatments for diseases. However, main weak points of animal experimentation include: (1) the influence of laboratory environment and other variables on animal study outcomes; (2) recognized differences between animal models of disease and human diseases; (3} specie specific physiology and genetics; (4) the large use of experimental animals in basic and applied research, associated with animal suffering.
Based on EU Directive 2010163, alternative methods for preclinical validation are under development or - in a few cases - have been already approved , to Replace,
Reduce and Refine animal testing according to the 3Rs Principle (Replacement, Reduction and Refinement) (lntroduction of the course). After this introduction, in vivo animal trials will be illustrated including animal welfare principles and applicative examples.
Alternative preclinical testing methods currently under development will be illustrated, including:
- Traditional 2D in vitro models
- 3D in vitro models: spheroids and organoids (definition and main uses; examples from literature ); wider part on in vitro models by tissue engineering approaches (characteristics and main uses: examples from literature ) with focus on skin and cardiac tissue engineering; brief and general outlook of characteristics and main uses of organ-on-chips models.
- Classroom practical exercises on statistical analysis of data from in vitro models.
Some of the models will be described/prepared in practical lectures hold in the laboratories. Typical in vitro assays exploited for experimental 3D in vitro model characterizations will be described in the classrooms and in practical lectures in the laboratories.
Additionally, students will learn how also in vitro tests can involve the use of animals, through the use of animals-derived media or materials, and the need for a paradigm shift.
In silico models will be also described including molecular and computational approaches in support of 3Rs principle, involving a practical part with classroom exercises (15 hours)
Seminars/webinars from Biomedical Industries working in the sector of in silico and in vitro models will be hold.
The course will have practical activities in the laboratory which will also help the students to develop their exam project and to better understand the in vitro models.
The course aims at providing knowledge in the field of the design of models for the preclinical testing of biomedical implants, drugs and advanced therapies. Innovations in preclinical models, stimulated by EU regulation, will prospect new work opportunities for Biomedical Engineers.
Currently, preclinical investigations on biomedical implants, drugs and advanced therapies proceed through initial in vitro trails, using 2D human cell cultures, followed by in vivo animal tests. However, 2D human cell culture models are not able to closely reproduce cell-cell and cell-extracellular matrix interactions present in human tissues, which indeed possess a 3D complex structure. Animal experiments have greatly contributed to the understanding of the mechanisms of diseases and to the study of new treatments for diseases. However, main weak points of animal experimentation include: (1) the influence of laboratory environment and other variables on animal study outcomes; (2) recognized differences between animal models of diseases and human diseases; (3} specie-specific physiology and genetics; (4) the large use of experimental animals in basic and applied research, associated with animal suffering.
Based on EU Directive 2010/63, alternative methods for preclinical validation are under development or - in a few cases - have been already approved , to Replace, Reduce and Refine animal testing according to the 3Rs Principle (Replacement, Reduction and Refinement) (as analysed in the lntroduction of the course). Alternative preclinical testing methods currently under development will be then illustrated in the course as described below.
During 2024/25 academic year, the in vitro modelling part will be further expanded.
PART 1 - IN VITRO MODELS:
- Traditional 2D in vitro models and use of animals-derived components in cultures, underlining the need for a paradigm shift.
- 3D in vitro models: spheroids, organoids and organs-on-chip (definition and main uses) with focus on in vitro models by tissue engineering approaches (particularly skin tissue engineering) and applications of organoids.
- Understanding the effect of 3D versus 2D cultures on cell behaviour.
- Analysis of in vitro models and methods for their validation by practical lectures in laboratory. Typical in vitro cell assays exploited for 3D in vitro model characterizations will be described in the classrooms during lectures and, then, explored in practical lectures in laboratory.
- Case studies: Models of healthy and pathological cardiac tissue, skeletal muscle, bone tissue in preparation to the project exam.
- External seminars by expert academics and company representatives: Models of blood brain barrier, esophageous tissue, human mucosa tissue; advanced devices to assess the functionality of excitable tissues (cardiac and nervous tissue); multidisciplinary approaches involving AI, in silico and in chemico models.
PART 2 - STUDENTS' PROJECTS
After a first part (approx. first 4-5 weeks ) dedicated to in vitro experimental models and lab exercises, the rules for Exam Project will be the subject of a lecture, followed by a number of lectures dedicated to project implementation in the classroom under teachers' supervision.
In parallel, lectures on the different tissue models and seminars will get an insight into the group project topics (following the course programme).
PART 3 - IN VIVO ANIMAL MODELS
Basic knowledge on in vivo models will be provided, including principles of animal welfare and main animal models used for preclinical validation of regenerative medicine solutions.
EXTERNAL ACTIVITIES
During the course, exernal activity in the form of seminars/webinars from researchers and Biomedical Industries working in the sector of tissue modelling will be held.
PRACTICAL ACTIVITIES
The course will have practical activities in classrooms and in laboratory which will also help the students to better understand tissue modelling and their exploitation and to carry out their project.
Learning Outcomes include knowledge on:
1) 3R Principle and Directive 2010163; methods of refinement and reduction in the planning of animal studies; replacement methods for safety and
biocompatibility assessments: potentialities and limitations.
2) Preclinical experimental models in vivo (animal trials) and their integration with in vitro cell trials with examples of mouse models of human diseases
3) Protection of animal welfare in European legislation, according to the animal species and their native social organization.
4) Experimental in vitro models and their most recent applications: 2D cultures and 3D models with practical laboratories
5) Statistical analysis of experimental data from testing in in vitro models: procedure for data analysis (basic knowledge)
6} In silico models in preclinical experimentation and their main recent applications.
The ability to apply the knowledge and understanding of the topics will be gained through classroom discussions during the development of projects and the analysis of scientific literature.
The teachers will give tips for excellent scientific presentations and project writing, which could be beneficial for the final thesis activity.
The students will learn group working and will visit the laboratories for practical lectures to better learn the theoretical concepts.
Learning Outcomes include knowledge on:
1) 3R Principle and Directive 2010 / 63; methods of refinement and reduction in the planning of animal studies; replacement methods for safety and biocompatibility assessments: potentialities and limitations.
2) Basic concenpts on preclinical experimental models in vivo (animal trials) and their integration with in vitro cell trials.
3) Protection of animal welfare in European legislation, according to the animal species and their native social organization.
4) Experimental in vitro models, including recently validated ones, for preclinical investigation: 2D cultures and 3D models with practical laboratories
5) Ability to perform project activity in group: interaction with other students for getting information, project writing and oral presentation.
6) Interaction with external experts and companies in the field, through seminars/webinars.
Furthermore, practical lectures in classrooms and in the laboratories will be useful to consolidate the theoretical concepts.
The ability to apply the knowledge and understanding will also be gained through classroom discussions during the development of projects and the critical analysis of scientific literature and students' ideas.
The teachers will give tips for excellent scientific presentations and project writing, which could be beneficial for further activities by the students beyond the course (e.g., final thesis activity).
1) Basic knowledge of general chemistry, organic chemistry and biochemistry.
2) Basic knowledge of science and technology of inorganic and polymeric materials.
3) Basic knowledge of cell biology and physiology.
4) Basic knowledge of techniques for determining the surface and massive properties of materials.
5) Basic knowledge of mechanics of fluids and solids
6) Knowledge on Tissue Engineering principles
lf some knowledge is missing, the teachers will provide additional information to students requiring them.
Teachers will provide complementary video lectures on basic cell biology including inner cell pathways discussed during lectures.
Such video lectures will be uploaded on the portal.
1) Basic knowledge of general chemistry, organic chemistry and biochemistry.
2) Basic knowledge of science and technology of inorganic and polymeric materials.
3) Basic knowledge of cell biology and physiology.
4) Basic knowledge of techniques for determining the surface and massive properties of materials.
5) Basic knowledge on Tissue Engineering principles
lf some knowledge is missing, the teachers will provide additional information to students requiring them.
1) lntroduction and European Standards for preclinical experimentation
2) Animal models, principles for the protection of animal welfare in EU
3) Brief recall on cell biology (supplemented by additional video lectures loaded on the course portal for those students who require such knowledge)
4) In vitro experimental models (2D vs. 3D models); biologicaI assays exploited in in vitro models
5) Computational fluidodynamic and molecular models in preclinical (and clinical) experimentation and their main applications
6) Statistical analysis of experimental data: software and practical methods
7) Laboratory activities on experimental in vitro models
8) Group work for the project exam
1) lntroduction and European Standards for preclinical experimentation
2) Brief recall on cell biology and introduction of in vitro experimental models (2D vs. 3D models); biologicaI assays exploited in in vitro models
3) 2D versus 3D cultures: why 3D models are more predictive.
4) Focus on in vitro tissue engineered skin models: preparation, validation and use; commercially available and approved skin models for preclinical investigation.
5) Focus on organoids
6) Case studies on tissue engineered models of other human tissues: cardiac tissue, skeletal muscle and bone tissue.
7) Laboratory activities on experimental in vitro models in groups.
8) Presentation of Exam Project work: details on the activity and documents (project text and presentation) to be prepared for the exam.
9) Presentation of the Exam Project topics: overview and their assignment to students' groups; Q&A session.
10) Basic part on in vivo animal models: overview, animal welfare principles, examples.
11) Seminars by academic experts and company representatives on tissue modelling, also involving complementary approaches (in silico, in chemico, role of AI).
12) Group work for the project exam during the course lectures, under the supervision and guide by the main teacher and the collaborators.
The course collects interdisciplinary topics and different teachers participate with their own block of lectures. There are 4 main blocks of subjects (animal trials, in vitro experimental models, in silico models and laboratory activities)
The official language is English. lf foreign students are not attending the course, it will be possible to hold part of the most complex theoretical lectures in ltalian on request by students.
The course collects interdisciplinary topics and different teachers participate with their own block of lectures. External activities (seminars/webinars) and laboratory/exercise activities are also included in the course.
The official language is English. lf foreign students are not attending the course, it will be possible to hold part of the most complex theoretical lectures in ltalian on request by students.
This course is ideal at the second year of Master Degree Course in Biomedical Engineering. However it is possible to follow the course also during the first year. Students from Bionanotechnologies, Biomechanics, Biomedical Instrumentation and E-health are welcome to attend the course. The teachers will be available to provide additional support to any student with limited background on Tissue Engineering.
Classroom lessons with slides project on (37.5 hours)
• Lab or practical lectures (13.5 hours)
• Classroom exercises: Q&A sessions and exercises (9 hours )
Theoretical classroom lessons with slides including seminars and webinars (42 hours)*.
Exercise lecture (divided into 2 groups):
• Lab practical lectures (9 hours).
• Classroom exercises: Q&A sessions and exercises (9 hours ).
*The theoretical lectures also include the activity dedicated to exam project explanation, introduction and execution.
• Slides and articles or material uploaded by the teachers
• Your own notes during lectures in the lab
• Slides and articles or material uploaded by the teachers
• Your own notes collected during lectures in the lab
Slides;
Lecture slides;
Modalità di esame: Prova orale obbligatoria; Elaborato progettuale in gruppo;
Exam: Compulsory oral exam; Group project;
...
The exam consists of the preparation of a group project by 4-5 students on a topic in the field of 3Rs-Principle, assigned during the course.
The exam aims to improve students' ability to:
- perform a research work in a group,
- design a research work which in compliance with the 3Rs Principle,
- acquire more knowledge on research methods (such as the tools available for literature research, the structure of a research activity plan, etc.),
- elaborate a plan for research work in both written and oral form,
- improve their oral and written communication skills,
- promote interactions with other students and with teachers.
Students will decide the group composition, while project topic will be selected among a list of topics provided by the teacher.
Concerning the project topic, students will have the possibility to discuss it with the teachers during planned meetings. Part of the lectures will be also dedicated to project discussion and development.
Project exam consists of:
1) a project document (with page limitations) in English, following guidelines provided by the teachers during lectures and planned meetings and strictly following a template provided by the main teacher. Such document should be sent to teacher no later than 7 days before the date of the oral exam.
2) A ppt presentation with slides in English to be sent to the teacher by the day before the exam. The presentation should last 15 minutes. The presentation is in English. One student in the group will present the project. After, a series of questions will be done to each student in the group by the examination board.
Examination board will consist of at least 3 teachers. The examination board will make questions on the presentation and project.
The teachers will evaluate:
- originality and feasibility of the group project (max 6 points)
- Aims and Workplan (compliant with 3Rs principles) (max 8 points)
- Students’ interaction during project (max 5 points)
- Bonus for lack of mistakes in the project and/or outstanding project idea (up to 2 points)
- Presentation (quality of the slides, clarity and completeness of the presentation) & questions on the project (12 points)
The mark will be differentiated among students in the same group by their answers to questions.
Exam is passed if the students reach a mark equaI or superior to 18.
The maximum mark 30L is possible if the student has a mark of at least 30.5.
The ONSITE exam will be hold in a classroom. The duration is approximately 1 h - 1,5 h per group.
Gli studenti e le studentesse con disabilità o con Disturbi Specifici di Apprendimento (DSA), oltre alla segnalazione tramite procedura informatizzata, sono invitati a comunicare anche direttamente al/la docente titolare dell'insegnamento, con un preavviso non inferiore ad una settimana dall'avvio della sessione d'esame, gli strumenti compensativi concordati con l'Unità Special Needs, al fine di permettere al/la docente la declinazione più idonea in riferimento alla specifica tipologia di esame.
Exam: Compulsory oral exam; Group project;
The exam consists of the preparation of a group project by 4-5 students on a topic in the field of 3Rs-Principle, assigned by the teacher during the course.
The exam aims to improve students' ability to:
- perform a research work in a group,
- design a research work in compliance with the 3Rs Principle,
- acquire more knowledge on research methods (such as the tools available for literature research, the structure of a research activity plan, etc.),
- elaborate a plan for research work in both written and oral form,
- improve oral and written communication skills,
- promote interactions with other students and with teachers.
Students will decide the group composition, while project topic will be selected among a list of topics provided by the teacher.
Part of the lectures will be dedicated to project discussion and development.
Project exam consists of:
1) a project document (with page limitations) in English, following guidelines provided by the teachers during lectures and any additional planned meeting (on request by students), and strictly following a template provided by the main teacher. Such document should be sent to teacher no later than 7 days before the date of the oral exam.
2) A ppt presentation with slides in English to be sent to the teacher by the day before the exam. The presentation should last 15 minutes. The presentation is in English. Each student of the group will present a short part of project slides following a random sequence decided by the teacher during the exam. After the presentation, a series of questions will be asked to each student in the group by the examination board.
Examination board will consist of at least 3 teachers. The examination board will make questions on the presentation and project.
The teachers will evaluate:
- originality and feasibility of the group project (max 4 points)
- Multidisciplinarity of the project (max 4 points)
- Aims and Workplan (compliant with 3Rs principles) + exploitation of knowledge by seminars/webinars/lab exercises (max 6 points)
- Students’ interaction during project development (max 4 points)
- Bonus for lack of mistakes in the project and/or outstanding project idea (up to 2 points)
- Presentation (quality of the slides, clarity and completeness of the presentation; max 6 points) & questions on the project (max 6 points) (max 12 points).
The mark will be differentiated among the students in the same group based on the presentation quality and their answers to questions.
Exam is passed if the students reach a mark equaI or superior to 18.
The maximum mark 30L is possible if the student receives a mark of at least 30.5.
The ONSITE exam will be held in a classroom. The duration is approximately 1 h per group.
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.