Co-delivery of VEGF and bFGF via a PLGA nanoparticle-modified BAM for effective contracture inhibition of regenerated bladder tissue in rabbits

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.

Experimental bladder regeneration using a poly-L-lactide/silk fibroin scaffold seeded with nanoparticle-labeled allogenic bone marrow stromal cells

“…Another possible approach to stimulate bladder regeneration in vivo could be based on application of various agents (eg, cytokines, growth factors) that promote cellular ingrowth from the native bladder wall. [44][45][46] Thus, in the recently published study by Xiong et al the authors introduced vascular endothelial growth factor-loaded poly(lactic-co-glycolic acid) nanoparticles for long-term sustained release in bladder acellular matrix allografts in a swine model. 44 Implantation of this scaffold resulted in increased angiogenesis that reduced contracture during bladder regeneration.…”

Whyever bladder tissue engineering clinical applications still remain unusual even though many intriguing technological advances have been reached?

“…It is resulting, indeed, from thorough studies in animal models, that a properly structured graft functional vascular network is essential, by suitable supply of oxygen and nutriens, for graft-host post-implant integration and tissue engineered survival (9). In this regard, recent studies show that the use of BAM allografts provided with VEGF (vascular endothelial growth factor) -and bFGF (basic fibroblast growth factor) loated PLGA (polylactic-co-glycolic acid) nanoparticles can rapidly restore graft vascularization meanwhile inhibiting contracture of regenerated bladder tissue in augmentation cystoplasties (10). What seems to be also reached by incorporation of trophic growth factors, among which VEGF and NGF, into cell seeded either BAM-or smart material-based scaffolds, leading to effective graft vascularization and innervation (11,16,52).…”

Stem Cells in Functional Bladder Engineering

“…The standard procedures in TE to facilitate angiogenesis into a bioengineered scaffold utilize VEGF and bFGF [4,29,30]. Other growth factors, such as angiopoietin 1 and 2, PDGF and TGF-β have also been considered due to their direct and indirect pro-angiogenic effects in vivo [92].…”

“…Additionally, recent novel tools and techniques added to the expanding list of possibilities, with the most promising ones coming from the field of nanotechnology. Nanostructured co-polymers [10], nano-sized ECM coatings on synthetic polymers [31], and combinations of growth factor-laden synthetic nanoparticles with bladder acellular matrix for their directed delivery [29] are just a few examples.…”

“…Beside structural alterations, such changes in porosity [28] the use of VEGF, bFGF [29,30], and other growth factors has been a common practice. Additionally, recent novel tools and techniques added to the expanding list of possibilities, with the most promising ones coming from the field of nanotechnology.…”