This work is designed to improve surgical treatment of number of congenital and acquired diseases of the urinary bladder in children and adults.
These bladder conditions are characterised by small contracted bladders that are susceptible to recurrent infections and create high pressure systems that can cause irreversible damage to the kidneys. The purpose of reconstructive surgery carried out in such conditions is to prevent irreversible kidney damage.
Plan of work and impact of our studies
The work proposed here is to test the concept that an improved surgical procedure to expand the bladder and cover it with a natural biomaterial will increase bladder capacity and hence prevent irreversible kidney damage. Using tissue engineering techniques we have previously developed a procedure to decellularised porcine bladders that generates a full thickness porcine acellular bladder matrix (PABM) which retains the compliant material properties of the bladder. Recently, we have also made significant progress in converting the original bladder decellularisation protocol into a procedure more suitable for batch production of the material, so that off-the-shelf material can be made available for surgeons to use in the clinical setting. Therefore, we believe that surgical implantation of PABM in bladder will provide a useful tool to treat many bladder conditions in children and adults. We are proposing to create an abnormality in the bladder wall of a 25-30 kg pig that will reflect the situation in a diseased bladder in humans and overlay with PABM to study if it will integrate into the bladder wall in 3 to 4 months. We will study whether integration occurs better when we combine the PABM with omentum as a source of growth factors for blood vessel growth. In the long-term, this work will be a step forward in solving a major unmet clinical need as a tissue-integrative patch material in urinary bladder repair in humans.
We propose to use 12 pigs in total in two batches of six. We will perform surgery in the first batch of six pigs (with and without omentum) and monitor these pigs for up to four months. With optimum care provided in the animal facility, these pigs will tolerate and recover from surgical procedure in the same way as children do. After this period, pigs will be humanely killed and tissues removed for close histological examination to study if PABM has indeed incorporated in the bladder wall. At this stage if we find that our result does not match our expectations then the project will be stopped and no further surgery will be performed until we can address any issues. Otherwise we will proceed with a further series of animals, adapting the procedure if required, in order to ensure that the results are reproducible and robust. All surgeries will be under complete aseptic conditions and good infection and pain control measures will be in place.
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