Double-Layer Nanofibrous Sponge Tube via Electrospun Fiber and Yarn for Promoting Urethral Regeneration

Abstract

Insufficient bionic performance is a structural obstacle and makes urethral repair unobtainable. To overcome this challenge, we mimicked the urethral matrix and applied two electrospinning techniques to build a double-layer sponge tube of nanofibers and nanoyarns. Intriguingly, silk fibroin (SF) and vitamin B5 (VitB5) could be introduced to increase the elasticity of the outer layer and reduce the hydrophobicity to further improve mesenchymal cell proliferation. Systematic experiments validated the bionic structure, biocompatibility, and exosome delivery capacity in this scaffold. We achieved scarless urethral repair by delivering the bioactive growth factors from adipose-derived stem cell exosomes by physical absorption. Biological regeneration of the urethra can be accomplished with continuous epithelium in animals. Furthermore, bioinformatics studies revealed that the expression of cell proliferation and fibrotic genes (e.g., Wnt7a, cfa-miR-574) was responsible for the biological regeneration of the adipose-derived stem cells exosomes (ADSC-exos) by delivering poly l-lactide-co-caprolactone/SF/VitB5 bilayer sponge (PSVBS) via reduced fibrosis gene expression, as well as improved epithelial formation and blood vessel formation. Therefore, the PSVBS design appeared to be an instructive approach for urethral and other tubular organ regeneration.

Graphical Abstract

TOC figure: The electrospun double-layer sponge fabricated by electrospinning simulated the microstructure of the urethra. The sponge can deliver the exosomes through a physical absorption style. The P(LLA-CL)/SF/VitB5 bilayer sponge has great potential to promote vascular regeneration and wound healing and can effectively inhibit fibrosis.

Funding

National Natural Science Fund of China(81700590); Shanghai Jiao Tong University Biomedical Engineering Cross Research Foundation(YG2017QN15); Shanghai health committee(20184Y0053); Jiangsu Key R&D Plan(BE2017664); The Talent Program of Shanghai University of Engineering Science(QNTD202104); Shanghai Local Universities Capacity Building Project of Science and Technology Innovation Action Program(21010501700)