Human Urine-derived Stem Cells Seeded Surface Modified Composite Scaffold Grafts for Bladder Reconstruction in a Rat Model

Abstract

We conducted this study to investigate the synergistic effect of human urine-derived stem cells (USCs) and surface modified composite scaffold for bladder reconstruction in a rat model. The composite scaffold (Polycaprolactone/Pluronic F127/3 wt% bladder submucosa matrix) was fabricated using an immersion precipitation method, and heparin was immobilized on the surface via covalent conjugation. Basic fibroblast growth factor (bFGF) was loaded onto the heparin-immobilized scaffold by a simple dipping method. In maximal bladder capacity and compliance analysis at 8 weeks post operation, the USCsscaffold(heparin-bFGF) group showed significant functional improvement (2.34 +/- 0.25 mL and 55.09 +/- 11.81 mu L/cm H2O) compared to the other groups (2.60 +/- 0.23 mL and 56.14 +/- 9.00 mu L/cm H2O for the control group, 1.46 +/- 0.18 mL and 34.27 +/- 4.42 mu L/cm H2O for the partial cystectomy group, 1.76 +/- 0.22 mL and 35.62 +/- 6.69 mu L/cm H2O for the scaffold group, and 1.92 +/- 0.29 mL and 40.74 +/- 7.88 mu L/cm H2O for the scaffold(heparin-bFGF) group, respectively). In histological and immunohistochemical analysis, the USC-scaffold(heparin-bFGF) group showed pronounced, well-differentiated, and organized smooth muscle bundle formation, a multi-layered and pan-cytokeratin-positive urothelium, and high condensation of submucosal area. The USCs seeded scaffold(heparin-bFGF) exhibits significantly increased bladder capacity, compliance, regeneration of smooth muscle tissue, multi-layered urothelium, and condensed submucosa layers at the in vivo study.