A modified small intestinal submucosa patch with multifunction to promote scarless repair and reinvigoration of urethra.

To reconstruct and restore the functions of male urethra is a challenging task for urologists. The acellular matrix graft currently used in the clinics is mono-functional and may cause a series of complications including stricture, fibrosis, and stone formation. As a result, such graft materials cannot meet the increasing demand for multifunctionality in the field of urethral tissue engineering. In this context, we have designed a multifunctional urethral patch with appropriate hydrophilicity, desirable antioxidant capacity and anti-inflammatory property for the repair of urethral defects. The multifunctional PCA/SIS patch was fabricated by mixing protocatechualdehyde (PCA), a naturally-occurring building block, with small intestinal submucosa (SIS) under an alkaline condition to allow cross-linking. As shown, the PCA/SIS patch has possessed outstanding mechanical strength, suitable hydrophilicity, good in vitro biodegradation property, excellent biocompatibility, antioxidant activity, and anti-inflammatory property. More importantly, this patch could remarkably promote the adhesion, proliferation and directional extension of rabbit bladder epithelial mucous cells (R-EMCs) as well as rabbit bladder smooth muscle cells (R-SMCs), and upregulate the expression of cytokeratin in the EMCs and contractile protein in the SMCs in vitro. In vivo experiments also confirmed that the PCA/SIS patch could significantly enhance scarless repair of urethral defects in rabbits by facilitating smooth muscle regeneration, reducing excessive collagen deposition and accelerating re-epithelialization and neovascularization. Taken together, the newly developed multifunctional PCA/SIS patch has provided a promising candidate for urethral regeneration. This article is protected by copyright. All rights reserved.