1 Trends in Regenerative Medicine Edited and presented by Sara Mantero 1 with the contribution of: M.Adelaide Asnaghi 1 , Gabriele Candiani 2 , Silvia Farè 1 , Gianfranco B.Fiore 1 , Paola Petrini 1 , Manuela T.Raimondi 3 , Monica Soncini 1 1) Dipartimento di Bioingegneria, Politecnico di Milano 2) Dipartimento di Chimica, Materiali e Ingegneria Chimica, Politecnico di Milano 3) Dipartimento di Ingegneria Strutturale, Politecnico di Milano Abstract— Regenerative medicine is a critical frontier in biomedical and clinical research. The great advances obtained in the last years were driven by a strong clinical need which could benefit of regenerative medicine outcomes for the treatment of a large number of conditions including birth defects, degenerative and neoplastic diseases, traumatic injuries. Regenerative medicine applies the principles of engineering and life sciences to enhance the comprehension of the fundamental biological mechanisms underlying the structure-function relationships in physiological and pathological tissues and to accomplish alternative strategies for developing in vitrobiological substitutes able to restore, maintain, or improve tissue and organ function. This paper reviews selected different approaches currently being investigated at Politecnico di Milano in the field of regenerative medicine. Specific tissue-oriented topics are divided in three sections according to each developmental stage: in vitrostudy, pre-clinical study and clinical application. In vitrostudies are aimed at investigating the basic phenomena related to gene delivery, stem cell behavior, tissue regeneration, and to explore dynamic culture potentiality in several different applications such as cardiac and skeletal muscle, cartilage, hematopoietic system, peripheral nerve and gene delivery. Some specific applicative fields of regenerative medicine, i.e., bone, blood vessels and ligaments enginee ring have already reached the prec linical stage providing promising insights for further research towards clinical applications. The translation of the results obtained during the in vitroand preclinical steps into clinical organ replacement is a very challenging issue, which can offer a valid alternative to fight morbidity, organ shortage and ethical-social problems associated with allotransplantation as shown in the clinical case reported in this review. I.I NTRODUCTIONEnd-stage organ failure or tissue loss is one of the most devastating and costly problem in medicine: over 8 million surgical procedures are estimated to be performed every year to treat these disorders in the United States alone, incurring a tremendous health care cost of more than $400 billion annually. Over the last 50 years, transplantation of a wide variety of tissues and organs, reconstructive surgical techniques and replacement with artificial devices have significantly improved patient outcomes. Unfortunately, these solutions suffer from many limitations, such as worsening donor shortages and lifelong immunosuppressive regimens, increased risk of infection, unwanted side effects and finite durability (Fuchs et al., 2001). Because of the above shortcomings, increasing interest has turned to the field of tissue engineering, which applies the principles of engineering and life sciences in an effort to reach a fundamental understanding of structure-function relationships in normal and pathological tissues and to develop in vitrobiological substitutes able to restore, maintain, or improve tissue and organ function (Vacanti and Langer, 1999). The basic principle is simple: cells collected from a patient or a donor are either introduced with or without modifying their properties into a three- dimensional supporting material (natural or synthetic) and cultured under proper environmental conditions (i.e., inside bioreactors). Once the tissue is fully mature or the number of cells adequate, engraftment may be performed. Another approach is represented by cell loaded injectable scaffolds: the use of hydrogels as support material allows cell survival in the aqueous-like environment associated with the possibility of releasing cell proliferation stimuli. Autologous and eterologous cell encapsulation is nowadays extensively studied for clinical application in functional organs substitution, recombinant cell transplantation in gene therapy or in muscle and cartilage regeneration to treat degenerative pathologies (Munarin et al., 2010; Petrini et al., 2010; Altomare et al., 2010a). Significant advances have already been achieved in the field and examples of successful clinical implementation of tissue-engineered products include skin substitutes (Priya et al., 2008), restoration of corneal surfaces, reconstruction of bone, cartilage, diseased bladder and trachea (Macchiarini et al., 2008; Martin et al., 2009). Engineering of more complex tissues and organs is obviously in an earlier stage of development, registering some progresses at the development of engineered gastrointestinal tract (Day, 2006), vascular grafts and heart valves (Schmidt et al., 2007). Recently, myocardium was developed on decellularised cadaveric hearts, shown to generate pump
