Abstract
Graft contracture is a common problem associated with the regeneration processes of tissue-engineered bladders. Currently, most strategies used for incorporating bioactive molecules into biomaterial designs do not work during all phases of tissue regeneration. In this study, we used a growth factor-PLGA nanoparticle thermo-sensitive gel system (i.e., BAM with incorporated VEGF and bFGF-loaded PLGA nanoparticles and mixed with a hydrophilic gel) to promote bladder tissue regeneration in a rabbit model. At 4 and 12 weeks after surgery, contracture rate assessment and histological examination were conducted to evaluate bladder tissue regeneration. The results indicated that the functional composite scaffold continuously and effectively released VEGF and bFGF and promoted bladder reconstruction with a significant decrease in graft contracture. In addition, the number and arrangement of regenerated urothelial cells and smooth muscle cells as well as microvascular density and maturity were improved in the VEGF/bFGF nanoparticle group compared with the single factor VEGF or bFGF nanoparticle group and BAM alone. The nanoparticle thermo-sensitive gel system, which exhibited favourable performance, may effectively inhibit graft contracture and promote bladder tissue regeneration in rabbits.
Highlights
Varieties of congenital and acquired bladder anomalies and diseases, such as neurogenic bladder, bladder exstrophy, or posterior urethral valves, may require augmentation cystoplasty[1]
The release period of bioactive components can be prolonged for a few days, but this extended period still cannot meet the physiological needs of the bladder tissue regeneration process, which usually lasts for weeks or months
Nanotechnology has emerged as a promising new strategy and has been incorporated into other biomaterials to continuously deliver biologically active molecules for enhanced bladder tissue regeneration[26,27,28]
Summary
Varieties of congenital and acquired bladder anomalies and diseases, such as neurogenic bladder, bladder exstrophy, or posterior urethral valves, may require augmentation cystoplasty[1]. One strategy to improve the outcome of bladder tissue regeneration is to incorporate a BAM with biologically active growth factors[15]. Numerous studies have demonstrated that vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) may enhance angiogenesis and smooth muscle regeneration in bladder replacement models[18,24,25]. We used a poly(lactic-co-glycolic acid) (PLGA) nanoparticle (NP)-modified BAM to co-deliver VEGF and bFGF in an effort to rapidly restore vascular networks and to effectively inhibit contracture in augmented bladders. The implanted scaffolds were analysed for graft contracture, host cell infiltration, vascularization, collagen degradation and deposition, and regenerated smooth muscle strip contractility
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