Tissue-engineering as an adjunct to pelvic reconstructive surgery: New potential concepts evaluated in animal studies

This PhD-thesis is based on animal studies and comprises three original papers and unpublished data. The studies were conducted during my employment as a research fellow at the Department of Obstetrics and Gynecology, Herlev University Hospital, Denmark.
New strategies for surgical reconstruction of pelvic organ prolapse (POP) are warranted. Traditional native tissue repair may be associated with poor long-term outcome and augmentation with permanent polypropylene meshes is associated with frequent and severe adverse effects. Tissue-engineering is a regenerative strategy that aims at creating functional tissue using stem cells, scaffolds and trophic factors. The aim of this thesis was to investigate the potential adjunctive use of a tissue-engineering technique for pelvic reconstructive surgery using two synthetic biodegradable materials; methoxypolyethyleneglycol-poly(lactic-co-glycolic acid) (MPEG-PLGA) and electrospun polycaprolactone (PCL) - with or without seeded muscle stem cells in the form of autologous fresh muscle fiber fragments (MFFs).To simulate different POP repair scenarios different animal models were used.
In Study 1 and 2, MPEG-PLGA was evaluated in a native tissue repair model and a partial defect model of the rat abdominal wall. We found that the scaffold was fully degraded after eight weeks. Cells from added MFFs could be traced and had resulted in the formation of new striated muscle fibers. Also, biomechanical changes were found in the groups with added MFFs.In Study 3, the long-term degradable electrospun PCL scaffold was evaluated in three rat abdominal wall models representing different loads on the scaffold. Surprisingly, cells from the MFFs did not survive. After eight weeks, a marked inflammatory foreign-body response was observed with numerous giant cells located between and around the PCL fibers which appeared not to be degraded. This response caused a considerable increase in the thickness of the mesh, resulting in a neo-tissue PCL construct with strength comparable to that of normal rat abdominal wall. The foreign-body inflammatory response did not differ between the groups in terms of cellularity, cell types or thickness, and no differences were found between groups when comparing biomechanical properties.
In study 4, we modified a new transabdominal rabbit vaginal model to avoid the erosions known to occur following vaginal mesh implantation. A partial defect was created on the anterior vaginal wall in the vesico-vaginal space and on the anterior vaginal wall close to the cervix. This was a feasibility study aimed at obtaining results comparable to those seen in the rat model. The model was easy to perform and no vaginal erosions were observed.