Biological Macromolecule-Based Scaffolds for Urethra Reconstruction

Abstract

Urethral reconstruction strategies are limited with many associated drawbacks. In this context, the main challenge is the unavailability of a suitable tissue that can endure urine exposure. However, most of the used tissues in clinical practices are non-specialized grafts that finally fail to prevent urine leakage. Tissue engineering has offered novel solutions to address this dilemma. In this technology, scaffolding biomaterials characteristics are of prime importance. Biological macromolecules are naturally derived polymers that have been extensively studied for various tissue engineering applications. This review discusses the recent advances, applications, and challenges of biological macromolecule-based scaffolds in urethral reconstruction.

Keywords: biological macromolecules; tissue engineering; urethra defects; urethra reconstruction.

Figure 1

Illustration demonstrating the underlying processes of urethral stricture. Phase 1 displays a folding of the mucosal layer. At this stage, minor abnormalities in the transformed tissue result in the leakage of urine, triggering the initiation of a fibrotic response. Increased accumulation of extracellular matrix (ECM) components leads to the progression into subsequent phases of urethral stricture. Phase 2 depicts constriction resembling an iris. Phase 3 indicates that the fibrotic reaction has infiltrated the spongiosum, causing minimal fibrosis in the sponge-like tissue. Phase 4 represents a partial spongiofibrosis affecting the full thickness of the tissue. Phase 5 demonstrates the extension of fibrosis beyond the corpus spongiosum into surrounding tissues. Phase 6 signifies the development of a complex urethral stricture that may lead to the formation of a fistula. Adopted from reference [26].

Figure 2

The self-assembly method involves several steps for tissue production. First, mesenchymal cells are cultured in Petri dishes with a paper support and ascorbate (50 µg/mL) for 28 days. This leads to the formation of ECM sheets. These sheets are then superimposed and secured together using surgical clips, and mechanical compression is applied using metal weights (brown cubes). A sponge (the green spongy object) is put between the metal weights and the tissue to protect tissues against mechanical damage. The tissue construct consisting of ECM layers is then cultured to allow fusion between the layers. Next, epithelial cells (purple cells in the figure) are seeded onto the constructs and cultured to populate the surface. Once this is achieved, the cell-scaffold constructs are transferred to an air–liquid interface, which promotes the maturation of the epithelium (yellow cells in the figure). The entire production process takes approximately 60 days. Adopted from references [57,58].