Decellularized Scaffolds with Double-Layer Aligned Microchannels Induce the Oriented Growth of Bladder Smooth Muscle Cells: toward Urethral and Ureteral Reconstruction.

There is a great clinical need for regenerating the urinary tissue. Native urethra and ureter have bidirectional aligned smooth muscle cells (SMCs) layers, which plays a pivotal role for micturition and transport the urine and inhibit reflux. Up to now, urinary scaffolds have not been designed to induce the native-mimicking aligned arrangement of SMCs. In this study, we engineered a tubular decellularized extracellular matrix (dECM) with an intact internal layer and bidirectional aligned microchannels in the tubular wall, which was realized by the subcutaneous implantation of a template, followed by the removal of the template, and decellularization. The dense and intact internal layer effectively increased the leakage pressure of the tubular dECM scaffolds. The rat-derived dECM scaffolds with three different sizes of microchannels were fabricated by tailoring the fiber diameter of the templates. The rat-derived dECM scaffolds exhibiting microchannels of ∼ 65 μm showed suitable mechanical properties, good ability to induce the bidirectional alignment and growth of human bladder SMCs (HBdSMC) and elevated higher functional protein expression in vitro. These data indicated that rat-derived tubular dECM scaffolds manifesting double-layer aligned microchannel may be promising candidates to induce the native-mimicking regeneration of SMCs in urethra and ureter reconstruction. This article is protected by copyright. All rights reserved.