Collagen scaffolds tethered with bFGF promote corpus spongiosum regeneration in a beagle model

Abstract

Regeneration of the corpus spongiosum helps prevent complications following urethral reconstruction, but currently there is a lack of effective therapeutic methods in clinic. In previous studies, we fabricated a fusion protein collagen-binding domain (CBD)-basic fibroblast growth factor (bFGF) that specifically binds to and releases from collagen biomaterials. We demonstrated that CBD-bFGF could promote angiogenesis and tissue regeneration in vivo. In this study, we established a beagle model with extensive urethral defects, and reconstructed the defects with collagen biomaterials that were unmodified or modified with CBD-bFGF. The results demonstrate that CBD-bFGF promotes corpus spongiosum regeneration resulting in improved outcomes following urethral reconstruction. Modifying collagen biomaterials with CBD-bFGF may represent an effective strategy for urethral substitution in urethral reconstruction.

Collagen biomaterials promote the regenerative repair of abdominal wall defects in Bama miniature pigs

“…Similarly, in the urethral cavernosum repair model and bladder reconstruction model, the CBD-bFGF dose of collagen scaffold was also 64 μg g −1 collagen membrane weight. 52,53 Previous experience suggests that at this dose, the N-terminal of bFGF can bind to the specific collagen binding domain to the greatest extent without affecting the factor activity. 28 High dose of bFGF, on the other hand, may lead to excessive fibroblast proliferation of and massive secretion of extracellular matrix.…”

Collagen-binding fibroblast growth factor ameliorates liver fibrosis in murine bile duct ligation injury

“…34,45,46 In previous studies, we showed that CBD-bFGF retained its biological activity, along with displaying controlled release and enhanced efficacy in vascular remodeling and tissue regeneration. 30,47,48 Notably, the beneficial effects of CBD-bFGF are partially due to the increasing collagen-binding ability, which provides a promising tissue targeting delivery system. 31,49 In the present study, our results demonstrate that CBD-bFGF could localize to the injury site with lesser diffusion than native bFGF.…”

Assessing the potential regeneration ability of corpus spongiosum in rabbit models

“…Red arrows and blue arrows: elastic fibres F I G U R E 6 Semi-quantitative analysis of collagen content, blood vessel density and smooth muscle content. *p < 0.05 versus Normal group; **p < 0.01 versus Normal group; # p < 0.05 versus Group A; ## p < 0.01 versus Group A Tang et al, 2018;de Vocht et al, 2018). Based on the importance of the CS to an integrated spongy urethra, we believe that improving regeneration of the CS through tissue engineering and regenerative medicine should be conducive to long-term functional recovery of the reconstructed urethra.…”

“…No significant blood sinusoids were observed. Collagen scaffold combined with basic fibroblast growth factor was also used to reconstruct spongy urethra in beagle model (Tang et al, 2018). The regeneration of smooth muscle tissue was significantly promoted, but only few dilated blood vessels, morphologically resembling little sinusoids, were detected in some sections.…”