Application of Bladder Acellular Matrix in Urinary Bladder Regeneration: The State of the Art and Future Directions

Table 2

Growth factors incorporated with bladder acellular matrix and their effects on urinary bladder regeneration.

Author, year; Reference no.	Growth factor	Growth factor incorporation technique	Experimental model	Urinary bladder regeneration
				BAM	BAM + exogenous growth; factors
Kanematsu et al. 2003 [22]	bFGF	Reswelling of the freeze-dried or not-freeze-dried BAM in PBS containing the bFGF radiolabeled with Na^125I by chloramine T.	Rat	(i) Graft shrinkage,; (ii) no differences in capacity, compliance, and max pressure between bladders augmented with BAM and BAM + bFGF,; (iii) complete regeneration of mucosal and smooth muscle layers at 12 weeks postoperatively (no differences between BAM and BAM + bFGF groups)	(i) Graft shrinkage was reduced (bFGF dose dependent manner) in BAM + bFGF compared to BAM group at 4 weeks postoperatively,; (ii) no differences in graft shrinkage between BAM and BAM + bFGF groups at 12 weeks postoperatively,; (iii) increased angiogenesis (bFGF dose dependent manner) in BAM + bFGF compared to BAM group
Youssif et al. 2005 [23]	VEGF	Incubation of BAM for 12 hours at 37°C in solution containing VEGF, additionally before implantation of the VEGF solution was injected into the 4 areas of the BAM	Rat	(i) No significant differences in bladder capacity, compliance, and intravesical pressure at 8 weeks postoperatively between BAM and BAM + VEGF groups,; (ii) completely regenerated urothelium at 2 weeks postoperatively (no differences between BAM and BAM + VEGF groups)	(i) Increased neovascularity in BAM + VEGF group compared to BAM group at all points of observation (2, 4, 8, and 12 weeks),; (ii) higher smooth muscle content in BAM + VEGF group compared to BAM group at all points of observation,; (iii) increased level of nerve fibers at 2, 4, and 8 weeks, but comparable at 12 weeks in the BAM + VEGF group compared to BAM group
Loai et al. 2010 [24]	VEGF	Lyophilized BAM was rehydrated in HA, dehydrated in ethanol, lyophilized for the second time, and then rehydrated in VEGF solution	Pig	(i) Poor organization of smooth muscle fibers in peripheral and central areas of the graft in BAM-HA and BAM groups at 10 weeks postoperatively,; (ii) lower expression of UPIII in urothelium of bladders augmented with BAM compared to BAM-HA-VEGF and BAM-HA	(i) Increased recellularization in BAM-HA-VEGF group compared to BAM-HA and BAM groups,; (ii) increased expression of angiogenic markers: CD31 and factor VIII in BAM-HA-VEGF group compared to BAM group,; (iii) well organized smooth muscles bundles comparable to native bladder in BAM-HA-VEGF group at 10 weeks postoperatively
Kikuno et al. 2009 [43]	NGF and VEGF	NGF and VEGF were injected into the 4 points of the bladder submucosa	Rat	(i) Urothelium covered completely the luminal surface of implanted BAM in all groups,; (ii) well defined smooth muscle layer was observed in all groups	(i) Bladder capacity and compliance were much higher in BAM + NGF + VEGF group compared with BAM + NGF, BAM + VEGF or BAM groups,; (ii) smooth muscle content and number of PGP 9.5 nerve fibers were significantly higher in BAM + NGF + VEGF compared to other groups

BAM, bladder acellular matrix; bFGF, basic fibroblast growth factor; HA, hyaluronic acid; NGF, nerve growth factor, PGP 9.5, protein gene product 9.5; PBS, phosphate buffered saline; VEGF, vascular endothelial growth factor.