Tissue Engineering for Congenital Anomalies concerning the Bladder and Abdominal Wall.
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[S.l. : s.n.]
Radboud Universiteit Nijmegen, 11 juli 2014
Promotores : Feitz, W.F.J., Wijnen, R.H.M. Co-promotores : Geutjes, P.J., Kuppevelt, A.H.M.S.M. van, Daamen, W.F.
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SubjectRadboudumc 10: Reconstructive and regenerative medicine RIMLS: Radboud Institute for Molecular Life Sciences
Severe congenital anomalies can have a large impact on the lives of patients. With tissue engineering techniques damaged or absent tissue can be regenerated, which can become a treatment option for congenital anomalies. In this thesis treatment possibilities for congenital anomalies concerning the bladder, for instance bladder exstrophy or myelomeningocele, and the abdominal wall, for instance gastroschisis, are described. A bladder exstrophy was surgically created in a fetal lamb, which largely resembled the anomaly in humans. In this model for diseased bladder we regenerated bladder tissue with a scaffold of bovine type I collagen, which served as an extracellular matrix. This tissue consisted of a urothelial layer, angiogenesis, smooth muscle cells and nerve fibers. The addition of growth factors improved angiogenesis, and the ingrowth of urothelium and smooth muscle cells. However, for a significant impact on clinical outcome, larger constructs need to be tested. A tubular collagen scaffold was combined with a polymer mesh and tested in a porcine model for its application as an incontinent urinary conduit, as an alternative for the current use of intestinal tissue. Although the construct served as a conduit in 50% of the animals, improvements need to be made before this technique can be studied in humans. In a fetal lamb model for gastroschisis the collagen scaffold was used to close the abdominal wall during the fetal period. Furthermore, we studied the coverage of the fetal bowel when it was left eviscerated outside the abdominal cavity. After birth less adhesions and fibrous peel was seen in the treated groups compared to the gastroschisis group. Skin and connective tissue with muscle cells replaced the scaffold. This treatment option may become an alternative for postnatal repair of abdominal wall defects when minimal invasive techniques (fetoscopy) improve, hereby decreasing the risk of premature delivery.
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