Urethral Reconstruction with Tissue-Engineered Human Amniotic Scaffold in Rabbit Urethral Injury Models

Abstract

BackgroundMitigating urethral injury remains a great challenge for urologists due to lack of ideal biomaterials for urethroplasty. The application of amniotic membrane (AM) over other synthetic materials makes it a better potential source for urethral reconstruction. We separated the basement layer of AM to obtain denuded human amniotic scaffold (dHAS) and then inoculated primary rabbit urethral epithelial cells on the surface of dHAS to determine whether this strategy minimizes potential rejection and maximizes the biocompatibility of human AM.Material/MethodsAfter the successful acquisition of dHAS from AM, cell-seeded dHAS were prepared and characterized. Both cell-seeded dHAS and acellular dHAS were subcutaneously implanted. Immune responses were compared by histological evaluation and CD4+ cell and CD8+ cell infiltrations. Then they were applied as urethroplastic materials in the rabbit models of urethral injury to fully explore the feasibility and efficacy of tissue-engineered dHAS xenografts in urethral substitution application.ResultsMild inflammatory infiltration was observed in cell-seeded dHAS grafts, as revealed by fewer accumulations of CD4+ cells and CD8+ cells (or neutrophils or other immune cells). Urethral defects of rabbits in the urethroplastic group with dHAS implantation (n=6) were completely resolved in 1 month, while there were 1 infection and 1 fistula in the control group with acellular dHAS patches (n=6). Histopathological analysis revealed mild immune response in the cell-seeded dHAS group (P<0.05).ConclusionsTissue-engineered dHAS minimizes potential rejection and maximizes the biocompatibility of AM, which makes it a potential ideal xenograft for urethral reconstruction.

The Cells and Extracellular Matrix of Human Amniotic Membrane Hinder the Growth and Invasive Potential of Bladder Urothelial Cancer Cells

“…Previously we have shown that hAM as a scaffold enables the development of tissue-engineered urothelium, which is in molecular and ultrastructural properties comparable to native urothelium (Jerman et al, 2014). Other studies have already used the hAM for bladder (Shakeri et al, 2008;Adamowicz et al, 2016;Barski et al, 2017) and urethral reconstruction (Shakeri et al, 2009;Wang et al, 2014) in animal models. Moreover, hAM was also used for reconstructive surgery of the ureteral obstruction in patients with extensive ureteral strictures (Koziak et al, 2007) and reconstructive surgery of strictured urethra (Koziak et al, 2004).…”

Repair of urethral defects by an adipose mesenchymal stem cell‑porous silk fibroin material

“…At present, it is still rather difficult to repair a long urethral defect. When the length exceeds 4 cm, additional tissue transplantation is in need ( 1 , 2 ). Researchers have endeavored to repair urethral defects by using various tissue materials, such as the foreskin, bladder mucosa, small intestinal submucosal tissue and tunica vaginalis.…”

Bladder Reconstruction with Human Amniotic Membrane in a Xenograft Rat Model: A Preclinical Study

“…The technique of applying HAMs in reconstructive urology was introduced for the first time in 1955 although only a few groups applied AM to repair the urinary tract wall 25. Reconstruction of urethrae with HAMs in a rabbit model showed a proper re-epithelialization, and even better results could be achieved with a denuded human amniotic scaffold inoculated with primary rabbit urethral epithelial cells 26, 27. A Polish group described a technique to supplement long ureteral wall strictures (5.5 cm) by using folded HAM allografts and presented good, sustainable results after an average follow-up period of 25.2 months 28.…”