Abstract
The unfavourable clinical outcomes of host cell-seeded scaffolds for bladder augmentation warrant improved bioactive biomaterials. This study aimed to examine the feasibility of adipose-derived stem cells (ASCs)-seeded bilayer bladder acellular matrix graft (BAMG)-silk fibroin (SF) scaffold in enhancing bladder reconstruction. Sprague Dawley rats were randomly divided into three groups: the BAMG-SF-ASCs group, the acellular BAMG-SF group and the cystotomy group. The BAMG-SF-ASCs group was sampled at 2, 4 and 12 weeks, and compared with the other groups at 12 weeks. In the BAMG-SF-ASCs group, the normal bladder contour was reformed similar to that in the cystotomy group, with abundant urothelium and smooth muscle regeneration, as well as a suitable scaffold degradation speed, and trivial fibrosis and inflammation. The ASCs seeded in BAMG-SF were maintained in the regenerated region during the 12-week experimental period and significantly enhanced the vessel density, nerve regeneration and bladder function compared with acellular BAMG-SF. In addition, the BAMG-SF-ASCs group presented elevated levels of SDF-1α, VEGF and their receptors, with an obvious increase in ERK 1/2 phosphorylation. BAMG-SF is a promising biomaterial for ASCs seeding to facilitate bladder augmentation and demonstrated an enhanced angiogenic potential possibly related to the SDF-1α/CXCR4 pathway via ERK 1/2 activation.
Highlights
Bladder augmentation is necessitated in various conditions, such as neurogenic bladder, bladder exstrophy, congenital bladder abnormalities, interstitial cystitis, and trauma, as well as cystectomy for bladder cancer [1]
adipose-derived stem cells (ASCs) were disseminated throughout the entire porous silk fibroin (SF) layer upon the relatively dense bladder acellular matrix graft (BAMG) layer, as shown by haematoxylin-eosin (H&E) stain (Figure 1I), www.impactjournals.com/oncotarget and these cells were viewed as separate cells or clusters in the fluorescent images of CM-DiI-stained samples counterstained by 4′,6-diamidino-2-phenyllindole (DAPI) (Figure 1J)
The superior combination of the structural strength and elasticity of BAMG-SF was not significantly altered by ASCs seeding for 3 days in vitro, with an elastic modulus of 12.32 ± 3.17 MPa and a max load of 5.53 ± 1.42 N
Summary
Bladder augmentation is necessitated in various conditions, such as neurogenic bladder, bladder exstrophy, congenital bladder abnormalities, interstitial cystitis, and trauma, as well as cystectomy for bladder cancer [1]. In the context of the eminent need for new alternatives to enterocystoplasty, tissue-engineered bladder augmentation holds great promise for overcoming the related obstacles and meeting this need. Contemporary www.impactjournals.com/oncotarget bladder tissue engineering strategies lack the ability to regenerate bladder smooth muscle and vasculature, and promote peripheral nerve tissue growth when using autologous cell populations. The favourable outcomes of this pilot study were later threatened by the results of the phase II study, which showed unsatisfactory bladder compliance after longterm follow-up with serious adverse events [4], as well as unbeneficial bladder compliance improvements and insufficient smooth muscle regeneration resulting from the simple application of an acellular collagen matrix in bladder augmentation for bladder exstrophy patients [5]
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