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

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.

Mechanical Characterization of the Male Lower Urinary Tract: Comparison among Soft Tissues from the Same Human Case Study

“…Characterization of the essential mechanical properties of the LUT may represent a key aspect for the development of effective in silico models to extend the experimental results to high-level scenarios providing additional information on LUT dysfunctions and reliable diagnostic and/or therapeutic tools for the urological clinical and surgical context [26][27][28]. The study and validation process of innovative procedures and devices for the treatment of LUT pathologies, such as balloon catheters for dilating urethral strictures or artificial sphincters for restoring urinary continence condition [29][30][31][32][33], needs to be considered according to the mechanical behavior of the biological tissues and structures involved, as well as the development and suitability of phantoms mimicking the tissue performance for surgical planning and training [34] and the tissue engineering for surgical reconstruction of anatomical or functional defects [35,36]. Institutional Review Board Statement: All procedures were conducted on human bodies from the "Donation to Science" Body Donation Program of the University of Padova and Veneto Region/National Reference Center for preserving and using gifted bodies.…”

Mesenchymal Stromal Cell Therapy for Thoracic Surgeons: An Update

“…One way to manage these limitations is human donor lung decellularization: this process, in fact, makes it possible to use an identical template of vascular and airway structures; however, if recellularization is not properly completed, extracellular matrix proteins will remain exposed, thus inducing a pathological reparative process in vivo, resulting in disruption of the extracellular matrix and scaffold degradation. Last but not least, the decellularization process requires human lung donors, so this technique does not solve the human organ shortage, highlighting the problem of xenogeneic scaffold use [88,89]. Recently, Shojaie et al studied the role of pulmonary extra-cellular matrix in the differentiation process of pluripotent cells in vitro, disclosing the strong inductive capacity of the native lung matrix alone.…”