Mesenchymal stem cell seeded knitted silk sling for the treatment of stress urinary incontinence.

Stress urinary incontinence remains a worldwide problem affecting patients of all ages. Implantation of suburethral sling is the cornerstone treatment. Current slings have inherent disadvantages. This study aims to develop a tissue engineered sling with bone marrow derived mesenchymal stem cell seeded degradable silk scaffold. The mesenchymal stem cells were obtained from Sprague-Dawley rats and were characterized in vitro. Layered cell sheets were formed after two weeks of culture and were labeled with carboxyfluorescein diacetate. Forty female rats were divided into four groups: Group A (n=5) had sham operation; other three groups underwent bilateral proximal sciatic nerve transection and were confirmed with stress urinary incontinence by the leak-point pressure measurement at 4 weeks after operation. Then, Group B (n=5) had no sling placed; Group C (n=15) was treated with a silk sling; and Group D (n=15) was treated with the tissue engineered sling. Histology and the leak-point pressure measurements were done at 4 and 12 weeks after the sling implantation while collagen content and mechanical testing were done at 12 weeks. The results showed that Group B had a significantly lower leak-point pressure (24.0+/-4.2 cmH(2)O) at 4 weeks (P<0.05), while Group C (38.0+/-3.3 cmH(2)O) and Group D (36.3+/-3.1 cmH(2)O) almost reached to the normal level shown by Group A (41.6+/-3.8 cmH(2)O) (p>0.05). At 12 weeks, tissue engineered sling of group D has higher collagen content (70.84+/-14.49 microg/mg) and failure force (2.436+/-0.192 N) when compared those of Group C (38.94+/-7.05 microg/mg and 1.521+/-0.087 N) (p<0.05). Both the silk sling and tissue engineered sling showed convincing functional effects for the treatment of stress urinary incontinence in a rat model. And the better ligament-like tissue formation in the tissue engineered sling suggested potential long-term function.