Abstract
The surgical reconstruction of ureteric defects is often associated with post-operative complications and requires additional medical care. Decellularized ureters originating from porcine donors could represent an alternative therapy. Our aim was to investigate the possibility of manufacturing decellularized ureters, the characteristics of the extracellular matrix (ECM) and the biocompatibility of these grafts in vitro/in vivo after treatment with different crosslinking agents. To achieve these goals, native ureters were obtained from pigs and were decellularized. The success of decellularization and the ECM composition were characterized by (immuno)histological staining methods and a DNA-assay. In vitro: scaffolds were crosslinked either with carbodiimide (CDI), genipin (GP), glutaraldehyde, left chemically untreated or were lyophilized. Scaffolds in each group were reseeded with Caco2, LS48, 3T3 cells, or native rat smooth muscle cells (SMC). After 2 weeks, the number of ingrown cells was quantified. In vivo: crosslinked scaffolds were implanted subcutaneously into rats and the type of infiltrating cells were determined after 1, 9, and 30 days. After decellularization, scaffold morphology and composition of ECM were maintained, all cellular components were removed, DNA destroyed and strongly reduced. In vitro: GP and CDI scaffolds revealed a higher number of ingrown 3T3 and SMC cells as compared to untreated scaffolds. In vivo: at day 30, implants were predominantly infiltrated by fibroblasts and M2 anti-inflammatory macrophages. A maximum of MMP3 was observed in the CDI group at day 30. TIMP1 was below the detection limit. In this study, we demonstrated the potential of decellularization to create biocompatible porcine ureteric grafts, whereas a CDI-crosslink may facilitate the remodeling process. The use of decellularized ureteric grafts may represent a novel therapeutic method in reconstruction of ureteric defects.
Highlights
The surgical removal of tissues or organs is an aggressive therapeutic strategy to treat innate or acquired pathologies of the urinary tract
Azan staining of natural (Figure 1A) and decellular ureteral scaffolds (Figure 1B) revealed morphologically intact structures, ideal matrix geometry, and no remaining cellular structures
In vitro biocompatibility, and immune response of tissue-engineered decellular porcine ureteral scaffolds, treated with different crosslinking agents
Summary
The surgical removal of tissues or organs is an aggressive therapeutic strategy to treat innate or acquired pathologies of the urinary tract. Various surgical techniques were employed such as the psoas hitch (Warwick and Worth, 1969), the Boari flap (Boari, 1894) and the downward mobilization of the respective kidney (Sullivan et al, 1982), as well as the replacement of the ureters with ileal or bladder tissue or even nephrectomy (del Pizzo et al, 1998; Corvin et al, 2004; Schlote et al, 2004; Wolff et al, 2011; Takeuchi et al, 2014) These surgical techniques were frequently accompanied by serious complications, ranging from mucus formation, stenosis, and infection to renal failure (Corvin et al, 2004; Schlote et al, 2004; Wolff et al, 2011). Tissue-engineered scaffolds may be an alternative in the surgical reconstruction of the urinary tract
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