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

Adv Healthc Mater. 2023 Oct;12(26):e2300544. doi: 10.1002/adhm.202300544. Epub 2023 Sep 10.

Abstract

There 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.

Keywords: bidirectional aligned microchannels; decellularized extracellular matrix; in vivo tissue engineering; ureter scaffolds; urethral scaffolds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Extracellular Matrix / metabolism
  • Humans
  • Myocytes, Smooth Muscle
  • Rats
  • Tissue Engineering
  • Tissue Scaffolds*
  • Ureter*
  • Urethra
  • Urinary Bladder