Research Area: Regenerative Medicine
Congenital Diaphragmatic Hernia (CDH) is a neonatal malformation that occurs during the diaphragmatic muscle development. Despite the advancement in the techniques of CDH treatment, the common use of synthetic implants (i.e. Gore-Tex) to repair the hernia is often followed by significant side effects, such as limited elasticity and lack of growth with the child, leading to subsequent muscle tears and implant failure. Hence, young patients need to undergo multiple surgeries, increasing each time the risk of complications and additional side effects. In the recent years, tissue engineering has brought significant improvements in the treatment of defects and congenital malformations in general. Unfortunately, the clinical application of biological materials obtained from tissues different from the skeletal muscle did not allow a clear improvement in the treatment of CDH, if compared to the common use of synthetic implants.
Our research group has recently shown that the use of a biological implant obtained through the decellularization of the diaphragmatic muscle greatly improves CDH treatment in an animal model, avoiding an extensive scar formation, and consequently limiting recurrences. Despite these important results, this classic tissue engineering approach requires long preparation times, depends on organ donation and cannot be used for large-scale production. Manifacturing a product that is standardized and identical for all patients is therefore not feasible.
As a research team, starting from the decellularized diaphragm extracellular matrix, the group aims at developing a biological ink mixed with cells that constitute the tissue under physiological conditions. This bioink is used for 3D printing of a construct through a printer developed for this purpose. The construct is then grown and matured inside a specific and homemade bioreactor. It is necessary, in fact, to stimulate the arrangement and alignment of the cells within the printed construct to obtain, at the end of the process, a diaphragm that resembles the original tissue as much as possible. The main objective is to obtain a specific and always identical biomaterial, to make its large-scale production and the manufacture of the construct finely tunable and automated through 3D printing, aiming at an even more personalized regenerative medicine treatment.
Edoardo Maghin PostDoctoral Researcher
Eugenia Carraro PhD Student
Generation of a Functioning and Self-Renewing Diaphragmatic Muscle Construct. Trevisan C, Fallas MEA, Maghin E, Franzin C, Pavan P, Caccin P, Chiavegato A, Carraro E, Boso D, Boldrin F, Caicci F, Bertin E, Urbani L, Milan A, Biz C, Lazzari L, De Coppi P, Pozzobon M, Piccoli M. Stem Cells Transl Med. 2019 Aug;8(8):858-869. doi: 10.1002/sctm.18-0206.
Allogenic tissue-specific decellularized scaffolds promote long-term muscle innervation and functional recovery in a surgical diaphragmatic hernia model. Trevisan C, Maghin E, Dedja A, Caccin P, de Cesare N, Franzin C, Boso D, Pesce P, Caicci F, Boldrin F, Urbani L, De Coppi P, Pozzobon M, Pavan P, Piccoli M. Acta Biomater. 2019 Apr 15;89:115-125. doi: 10.1016/j.actbio.2019.03.007.
A finite element analysis of diaphragmatic hernia repair on an animal model. de Cesare N, Trevisan C, Maghin E, Piccoli M, Pavan PG. J Mech Behav Biomed Mater. 2018 Oct;86:33-42. doi: 10.1016/j.jmbbm.2018.06.005.
Mouse Skeletal Muscle Decellularization. Piccoli M, Trevisan C, Maghin E, Franzin C, Pozzobon M. Methods Mol Biol. 2018;1577:87-93. doi: 10.1007/7651_2017_28.
Improvement of diaphragmatic performance through orthotopic application of decellularized extracellular matrix patch. Piccoli M, Urbani L, Alvarez-Fallas ME, Franzin C, Dedja A, Bertin E, Zuccolotto G, Rosato A, Pavan P, Elvassore N, De Coppi P, Pozzobon M. Biomaterials. 2016 Jan;74:245-55. doi: 10.1016/j.biomaterials.2015.10.005.
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