BIOARTIFICIAL SYSTEM COMPOSED BY MUSCLE ACELLULAR MATRIX, MUSCLE CELLS, AND VEGF-LOADED POROUS SILICA GEL FOR THE TREATMENT OF CONGENITAL DIAPHRAGMATIC HERNIA

Congenital diaphragmatic hernia is characterized by high mortality rate (40-50%), despite advances in obstetric management and neonatal intensive care. The use of synthetic patches, such as PTFE, Silastic, and Vicryl, to close the defect usually develops recurrence (50 to 80%) in the next months and scoliosis by the years, because the patch doesn’t grow meanwhile the thoracic cavity has been enlarging. The possibility to develop an engineered muscle, that could grow and move as the original diaphragm, is a fascinating idea. Actually, acellular matrices has been successfully employed for the regeneration of several tissues, such as bladder, skin, urethra, and small bowel, since they act as temporary scaffolds which during resorption generate new permanent tissue. Nevertheless, in our previuos works we have highlighted that homologous diaphragmatic acellular matrix is not able to support the reconstruction of skeletal muscle and that the presence of autologous muscle satellite cells previously seeded into the matrix represent an important factor to preserve the structural integrity and to improve in vivo biocompatibility of the implants. Starting from these considerations, in this work the possibility to culture muscle cells (obtained from stem cells of bone marrow or skeletal muscle) on muscle acellular matrices will be verified in order to obtain in vitro a diaphragm substitute. The cell-matrix construct will be then inserted in rabbit diaphragm in order to repair a defect previously created. The outcome of reconstructive surgery will be evaluated histologically at various times.