1. SUMMARY
Due to the aging of society and the growing number of oncology cases, there is a need
for new and efficient reconstruction techniques in urology. Native tissue is often not
available or can be in bad condition after multimodal treatments with surgery and
radio-chemotherapy. Various methods and materials have been developed to date to
replace the damaged tissues. The possible indications embrace the partial or complete
replacement of the ureter, bladder or urethra, repair of complex fistulas and protection
of anastomoses. One of the strongest tissues in the human body and one with multiple
growth factors, human amniotic membrane (HAM) could serve as a potential graft in
reconstructive urology. Amniotic tissue can be easily harvested during Caesarean
sections and is therefore broadly available. However, by now its application is limited
to cornea replacement and burn therapy. Therefore, our first aim was to develop a
manufacturer-independent, standardized in vitro process for the preparation of amnion
grafts. In this line, we planned to develop a sterilization and storage technique for
frozen and dried HAM with a preserved extracellular matrix. As a next step, we
employed an in vivo xenologous model to test previously constructed multilayer HAM
grafts and to investigate the capacity to repair small defects in the rat bladder and
intestinal tract. HAM provided a durable graft with good functional and histological
results for bladder grafting. The initial inflammatory reaction decreased, with no signs
of degradation observed over six weeks of follow-up and only subtle signs of graft
rejection detected. However, HAM was not suitable for intestinal reconstruction due
to an increased rate of adhesions. Next, by following the steps in the Innovation,
Development, Exploration, Assessment and Long-term Study for Devices (IDEAL-D)
system of surgical innovation, we defined possible human indications. The first-inhuman
stage of innovation involved clinical cases of complex fistulas, a vesico-vaginal
fistula and a chronic wound with an entero-cutaneous fistula, which were treated
successfully with HAM allografts. Based on the promising clinical data, further
directions could be planned, targeting ureteral reconstruction or the protection of
urethra anastomoses
