A Modified Small Intestinal Submucosa Patch with Multifunction to Promote Scarless Repair and Reinvigoration of Urethra

Abstract

To reconstruct and restore the functions of the 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, a multifunctional urethral patch is designed for the repair of urethral defects by mixing protocatechualdehyde (PCA) with small intestinal submucosa (SIS) under an alkalin condition to allow cross linking. As shown, the PCA/SIS patch possesses excellent biocompatibility, antioxidant activity, and anti‐inflammatory property. More importantly, this patch can 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 confirm that the PCA/SIS patch can 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 provides a promising candidate for urethral regeneration.

Four-dimensional Hydrogel Dressing Adaptable to the Urethral Microenvironment for Scarless Urethral Reconstruction

“…Recently, the development of tissue engineering methods that combine biocompatible scaffolds with adult cells or stem cells has effectively improved urethral repair, but clinical application is di cult due to ethical, cell colonization, and local survival problems 43,44 . Thus, current studies have focused on delivering biological factors with biocompatible scaffolds, especially hydrogel dressings, owing to the unique advantages of wet-healing conditions, the ease of carrying bioactive substances, and availiability to mimic the cell microenvironment.…”

The application of small intestinal submucosa in tissue regeneration

“…It is very convenient to control the physicochemical and biological properties of biomaterials because the distinct chemical structure of polyphenol materials (catechols, resorcinols, hydroglucinols, and hydroxyquinoline groups) can react with different molecules through covalent and non-covalent interactions [ 96 ]. The phenolic hydroxyl group of the polyphenol material can form hydrophobic bonds and hydrogen bonds with the proteins of the SIS scaffold, thereby improving the mechanical properties of the scaffold [ 97 ]. In recent years, polyphenolic compounds such as proanthocyanidins, quercetin, and genipine have been widely explored for SIS scaffold modification [ [98] , [99] , [100] ].…”

“…Li-Ping Huang et al described the production of multifunctional patches composed of PCA/SIS for mending urinary tract defects. The method involved blending protocatechinaldehyde (PCA) with the SIS of the small intestine in alkaline conditions to allow for cross-linking and to confer antioxidant and anti-inflammatory properties to SIS [ 97 ]. In vitro studies demonstrate that the patch greatly enhances adhesion, orientational extension, and proliferation of R-EMC and R-SMCs.…”