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.

自体组织移植的输尿管重建通常受到组织可用性和供体部位发病率的限制。本研究调查了无细胞双层丝素蛋白 (BLSF) 支架在猪输尿管成形术模型中的性能。在成年雌性尤卡坦小型猪中进行了 BLSF 移植物输尿管输尿管成形术和短暂支架置入术 8 周。N= 5）。使用超声检查和逆行输尿管肾盂造影术以 2 周和 4 周的间隔进行新导管成像，动物在术后保持 12 周。输尿管新组织和未手术对照的终点分析包括组织学、免疫组织化学 (IHC)、组织形态学评估以及离体收缩/松弛的功能评估。所有动物都存活到预定的安乐死，并在 8 周支架植入期间在重建的收集系统中显示出轻度肾积水（1-2 级），其中一只动物在术后 2 周出现持续性皮下瘘管。在支架植入 12 周后，80% 的猪在移植部位内部形成了严重的肾积水（4 级）和狭窄。在 60% 的导致输尿管梗阻的猪中，大量支架挤入远端输尿管也很明显。然而，组织学和 IHC 分析揭示了神经支配的、血管化的新组织的形成一个-平滑肌肌动蛋白 + 和 SM22α+ 平滑肌束以及尿斑蛋白 3A+ 和泛细胞角蛋白 + 尿路上皮。 离体新组织的收缩和松弛反应与未操作的控制段相似。BLSF 生物材料代表了管状输尿管成形术的新兴平台，但需要进一步优化以改善体内 降解动力学并减轻狭窄的形成。