Bladder regeneration by bladder acellular matrix combined with sustained release of exogenous growth factor.
OBJECTIVE
We investigate the use of bladder acellular matrix (BAM) as a carrier of exogenous growth factor.


METHODS
Basic fibroblast growth factor (bFGF) protein was loaded in a lyophilized BAM by rehydrating the matrix with the growth factor solution. In vitro and in vivo release of bFGF from BAM was traced by radiolabeled bFGF. To assess biological effect of the released bFGF, BAMs incorporating bFGF were implanted into back subcutis of mice and vascular endothelial growth factor levels in the local tissue were determined. Furthermore, bladder augmentation was performed in rats with BAM grafts containing various concentrations of bFGF. At 4 and 12 weeks the graft size at maximal cystometric capacity was evaluated, followed by histological and physiological evaluation.


RESULTS
Sustained release of bFGF from BAM was observed in vitro and in vivo. In vivo biological activity of bFGF in BAM as determined by vascular endothelial growth factor levels was preserved for more than 3 weeks. In the bladder augmentation model angiogenesis into the matrix was promoted and graft shrinkage was significantly inhibited by incorporated bFGF in a dose dependent manner at 4 weeks.


CONCLUSIONS
BAM can function as a platform for sustained release of exogenous bFGF. This delivery method of growth factor could be a useful tool for bladder reconstruction.
D000818:Animals; D001682:Biological Availability; D004337:Drug Carriers; D016228:Endothelial Growth Factors / Q000378:metabolism; D005109:Extracellular Matrix; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000493:pharmacokinetics / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000187:drug effects* / Q000502:physiology; D023822:Tissue Engineering; D001743:Urinary Bladder / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D004337:Drug Carriers; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2