Abstract
Ureteral reconstruction with autologous tissue grafts is often limited by tissue availability and donor site morbidity. This study investigates the performance of acellular, bi-layer silk fibroin (BLSF) scaffolds in a porcine model of ureteroplasty. Tubular ureteroplasty with BLSF grafts in combination with transient stenting for 8 weeks was performed in adult female, Yucatan, mini-swine (N = 5). Animals were maintained for 12 weeks post-op with imaging of neoconduits using ultrasonography and retrograde ureteropyelography carried out at 2 and 4 weeks intervals. End-point analyses of ureteral neotissues and unoperated controls included histological, immunohistochemical (IHC), histomorphometric evaluations as well as ex vivo functional assessments of contraction/relaxation. All animals survived until scheduled euthanasia and displayed mild hydronephrosis (Grades 1-2) in reconstructed collecting systems during the 8 weeks stenting period with one animal presenting with a persistent subcutaneous fistula at 2 weeks post-op. By 12 weeks of scaffold implantation, unstented neoconduits led to severe hydronephrosis (Grade 4) and stricture formation in the interior of graft sites in 80% of swine. Bulk scaffold extrusion into the distal ureter was also apparent in 60% of swine contributing to ureteral obstruction. However, histological and IHC analyses revealed the formation of innervated, vascularized neotissues with a-smooth muscle actin+ and SM22α+ smooth muscle bundles as well as uroplakin 3A+ and pan-cytokeratin + urothelium. Ex vivo contractility and relaxation responses of neotissues were similar to unoperated control segments. BLSF biomaterials represent emerging platforms for tubular ureteroplasty, however further optimization is needed to improve in vivo degradation kinetics and mitigate stricture formation.
Highlights
Ureteral injuries caused by intraoperative endourological maneuvers, radiation exposure, or gynecological procedures can lead to life-threatening complications such as sepsis, urinary tract obstruction, and loss of renal function (Packiam et al, 2016; Blackwell et al, 2018)
Tubular ureteroplasty with bi-layer silk fibroin (BLSF) grafts was performed in five swine in combination with transient ureteral stenting of the implantation site to reinforce initial neoconduit integrity (Table 1)
No signs of hydronephrosis were detected in any swine at time of ureteroplasty confirming normal anatomy of the collecting system
Summary
Ureteral injuries caused by intraoperative endourological maneuvers, radiation exposure, or gynecological procedures can lead to life-threatening complications such as sepsis, urinary tract obstruction, and loss of renal function (Packiam et al, 2016; Blackwell et al, 2018). The success of these strategies can be compromised by donor site morbidity, reflux, stricture formation, hydronephrosis, and persistent anastomotic leakage (Engel et al, 2015; Xiong et al, 2020; Heijkoop and Kahokehr, 2021) These complications often necessitate secondary salvage procedures to maintain upper urinary tract function, but in the worst case scenario, nephrectomy may be required (Onal et al, 2018; Vasudevan et al, 2019). These reports highlight the need for novel strategies for ureteral reconstruction which can minimize unwanted side-effects and promote functional tissue regeneration
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