“Designing TISSUE ENGINEERED MATERIALS for treating PELVIC ORGAN PROLAPSE"
Giulia Gigliobianco,Dr. CK Chong and Prof. Sheila MacNeil
The clinical problem and beneficiaries. Pelvic organ prolapsed affects >40% of women above 60 years, leading to distressing problems of stress urinary incontinence and prolapse. This condition is age-associated and increases with the number of pregnancies that a woman has experienced. The surgical demand for repair is increasing with an ageing population. Although there has been extensive work on a vast array of materials spanning synthetics, autografts, allografts and xenografts, there is no one material clinically recommended for the repair of pelvic floor. 30% of primary repairs recur so that implants were introduced, yielding better anatomical results. Utilization of transvaginal mesh is still however associated with 10% graft related complications due to inappropriate biocompatibility and poor biomechanical performance.
Background work. We have identified electrospun scaffold materials as suitable scaffolds and shown that cells will impregnate these scaffolds successfully and that we can produce materials which approximate to the biomechanical properties of the pelvic floor.
The aim of this project. We are seeking to make resorbable polylactic acid biodegradable meshes that have mechanical and physical characteristics closer to that of the native tissue we intend to repair.
The project challenges. The first step of the project will be to develop bioreactors that allow us to look critically at how culturing tissues under dynamic loading conditions (with respect to time, frequency and varying load) affects their development in vitro. Here we will look at the viability and proliferation of cells in the scaffold. We will look at the extracellular matrix proteins produced by the cells in the scaffold using conventional histology and confocal microscopy, examining collagens and elastin. We will also measure the biomechanical properties (e.g. uniaxial and biaxial tensile properties) of the tissues. Following on from that the challenge will be to develop second generation bioreactors that can be used to condition tissues that would be fit for purpose for clinical implantation.
Objectives of the project:
2. To develop a bioreactor for conditioning cells within the scaffolds
· Blackwood, K. A.; McKean, R.; Canton, I.; Freeman, C. O.; Franklin, K. L.; Cole, D.; Brook, I.; Farthing, P.; Rimmer, S.; Haycock, J. W.; Ryan, A. J.; MacNeil, S. (2008). “Development of biodegradable electrospun scaffolds for dermal replacement”. Biomaterials29: 3091-3104.
· Mangera, A., Bullock A.J., Chapple C.R., MacNeil, S. (2010). “Developing an autologous tissue engineered prosthesis for use in stress urinary incontinence and pelvic organ prolapse”. International Urogynecology Journal: neurology and Urodynamics29(6): 1129-1130.
Kroto Research Institute, University of Sheffield