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

Abstract

AbstractThere is a great clinical need for regenerating urinary tissue. Native urethras and ureters have bidirectional aligned smooth muscle cells (SMCs) layers, which plays a pivotal role in micturition and transporting urine and inhibiting reflux. Thus far, urinary scaffolds have not been designed to induce the native‐mimicking aligned arrangement of SMCs. In this study, a tubular decellularized extracellular matrix (dECM) with an intact internal layer and bidirectional aligned microchannels in the tubular wall, which is realized by the subcutaneous implantation of a template, followed by the removal of the template, and decellularization, is engineered. The dense and intact internal layer effectively increases the leakage pressure of the tubular dECM scaffolds. Rat‐derived dECM scaffolds with three different sizes of microchannels are fabricated by tailoring the fiber diameter of the templates. The rat‐derived dECM scaffolds exhibiting microchannels of ≈65 µm show suitable mechanical properties, good ability to induce the bidirectional alignment and growth of human bladder SMCs, and elevated higher functional protein expression in vitro. These data indicate that rat‐derived tubular dECM scaffolds manifesting double‐layer aligned microchannels may be promising candidates to induce the native‐mimicking regeneration of SMCs in urethra and ureter reconstruction.