Il volume “Scaffolds for Tissue Engineering. Biological Design Materials, and Fabrication” (Pan Stanford, 2014) raccoglie una serie di contributi scientifici di un settore di ricerca che per le sue applicazioni è destinato ad incidere sempre più profondamente sulla vita e sulla salute delle persone. L’opera è stata curata da Claudio Migliaresi, professore ordinario di Scienza e tecnologia dei materiali, e Antonella Motta, professore associato di Bioingegneria industriale, entrambi del Dipartimento di Ingegneria industriale dell’Università di Trento, che sono anche coautori di uno dei capitoli del libro.
Proponiamo, in lingua originale inglese, l’inizio del primo capitolo “An Evolving State of the Art in Tissue Engineering” di Anthony T. DiBenedetto.
Premise: An Evolving State of the Art in Tissue Engineering
A. T. DiBenedetto
Dr. Anthony Atala of the Wake Forest Institute for Regenerative Medicine in Winston-Salem, North Carolina, encountered a young patient, Luke Masella, with a life-threatening bladder condition that required an organ transplant. Parental permission was obtained to use the patient’s own cells in an experimental procedure to create a new bladder. Healthy muscle cells taken from the patient’s diseased bladder and urothelial cells from his urinary tract were multiplied by incubation in petri dishes and then applied to a balloon-shaped scaffold made from collagen and other biocompatible organic materials. The cellularized bladder scaffold was incubated in vitro at body temperature until the cells generated functioning tissues and then successfully transplanted at Boston Children’s Hospital in a procedure that took approximately 14 hours. At this writing, Luke is a healthy, physically active student at the University of Connecticut with the prospects of living a long and productive life. In 2003, a startup company, Tengion, was founded with an objective of advancing Dr. Atala’s basic and clinical research. A successful clinical trial of the use of a tissue-engineered organ in reconstructive surgery on seven patients with end-stage bladder disease was completed after 31 months, during which time the engineered ladders displayed normal behavior.
In 2008, a team of doctors, led by Surgeon Professor Paolo Macchiarini, of the Hospital Clinic of Barcelona, Spain, transplanted a tissue-engineered left bronchus into the windpipe of Claudio Castillo, a 30-year-old mother of two. She needed the transplant to save a lung after her air passage had been damaged by tuberculosis. To make the new bronchus, a donor windpipe was taken from a patient who had recently died. Scientists from the Politecnico di Milano, Italy, the University of Bristol, United Kingdom, and the University of Padua, Italy, assisted in the preparation of a new tissue-engineered bronchus using a portion of the harvested donor windpipe. Strong chemicals and enzymes were used to wash away all of the cells from the donor windpipe, or trachea, leaving only a decellularized tissue scaffold made of the fibrous protein collagen. Cells were taken from Ms. Castillo’s bone marrow and windpipe lining to create a tissue scaffold repopulated with Ms. Castillo’s own cells. After four days of growth in a rotating bioreactor, the newly formed donor bronchus was transplanted into Ms. Castillo. Four days after transplantation the hybrid windpipe was almost indistinguishable from adjacent normal airways. A biopsy of the site proved that the transplant had developed its own blood supply, with no signs of rejection.
Drs. Harald Ott and Doris Taylor and colleagues at the University of Minnesota harvested donor hearts from adult rats and removed all cells from the hearts by bathing them with a solution of detergent compounds. The decellularized matrix preserved the fibrous morphology and orientation of the myocardial/extracellular matrix (ECM) of the original heart, resulting in an authentic heart scaffold with blood vessels, heart valves, and an intact atrial and ventricular geometry that retained the architecture required to pump blood.
They seeded these scaffolds with cardiac cells from young healthy rats and maintained them in culture conditions in a bioreactor that simulated cardiac physiology. Four days later, they observed “contractions and, by day eight, their constructs could generate pump function equivalent to about 2% of adult heart function.” After a further period of time, both the larger cardiac vessels and the smaller third- and fourth-level branches were capable of supporting the expansions and contractions of a living heart. The techniques were also used to create “breathing rat lungs.” The work resulted in a start-up company called Miromatrix Inc. Shortly after that, a team from Massachusetts General Hospital and Harvard University used a mixture of stem cells from rats and humans to recellularize donor rat lungs and transplanted the resulting scaffolds into young rats. The lungs functioned for six hours, albeit imperfectly.
The three above-mentioned accomplishments are examples of a myriad of research and technological advancements that are now occurring in the 21st century. The concept of an interdisciplinary field of “tissue engineering” as a unique field of study was generated during a series of panel meetings and workshops sponsored by the National Science Foundation of the United States.
The widespread acceptance of the concept can be traced to Y.C. Fung of the University of California at San Diego, who proposed the idea at a 1988 NSF workshop held at Lake Granlibakken, California, and to Robert Langer and Joseph Vacanti, whose review article in Science promoted a rapid increase in collaborative research in the worlds of clinical medicine, developmental biology, biomaterials, biomechanics, and biomedical science and engineering.5 Studies in developmental biology of cell and tissue coalescence, cell adhesion, and the properties of embryonic tissues provided the biological foundation for modern tissue engineering. The possibility of engineering a tissue was demonstrated as early as 1930s,6,7 and fundamental studies of stressdependent morphogenetic effects in tissue remodeling,8–10 analytical modeling of cell movement, interstitial flow and deformation in an anisotropic ECM,11 and studies of morphogenetic processes in the growth of vascular networks12 all contributed to the early development of tissue-engineered scaffolds. Since then, there has been a dramatic increase in the imaging, modeling, and simulation of human anatomy and physiology, promoted by long range strategic plans for basic research in the biological sciences and medicine, for development of computer and engineering technologies related to public health, and by the Human Genome Project.4,13–15 Tissue Engineering as a field of study was defined as “an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function or a whole organ.”5 Research on the development of two-dimensional scaffolds containing cells on sheets of naturally occurring collagen and collagen–glycosaminoglycan composites for the regeneration of new skin was a precursor to the creation of three-dimensional (3D) scaffolds capable of housing the large numbers of cells required for regenerating other organs and functional tissues.7,16,17 A primary objective in the creation of functional tissue-engineered scaffolds has been to design 3D scaffolds that permit the production of ECM that mimic the ECM of the tissue being replaced or repaired. To accomplish that function, one must provide a mechanically stable environment that hosts the necessary cells, growth factors, and other biological components in a porous structure that allows cell migration, adhesion and proliferation, and vascularization of the growing tissue that mirror that of the original tissue.18 Critical issues have included enhancing cell survival, maintaining differentiated function, developing a significant cell mass, and achieving vascularization where required. Attempts to engineer functional tissues and organs during the period 1990–1999 included scaffolds to aid nerve regeneration, corneal implants, tissue-engineered liver implants, creation of an artificial pancreas, and the development of a urinary organ using bladder cells encased in a polymer composite matrix. During this period, considerable effort also focused on creating tissue-engineered blood vessels, heart valves, and polymer scaffolds for creating heart muscle tissue.
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