Evaluation of Bi-Layer Silk Fibroin Grafts for Tubular Ureteroplasty in a Porcine Defect Model.
Evaluation of Bi-Layer Silk Fibroin Grafts for Tubular Ureteroplasty in a Porcine Defect Model.
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DOI：
10.3389/fbioe.2021.723559
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发表时间：
2021
影响因子：
5.7
通讯作者：
Mauney JR
中科院分区：
文献类型：
--
作者：
Gundogdu G;Okhunov Z;Cristofaro V;Starek S;Veneri F;Orabi H;Jiang P;Sullivan MP;Mauney JR
自体组织移植输尿管重建常常受到组织可用性和供体部位发病率的限制。本研究探讨了脱细胞双层丝素蛋白（BLSF）支架在猪输尿管成形术模型中的性能。对成年雌性、尤卡坦、迷你猪（N = 5）进行小管输尿管成形术与BLSF移植物联合短暂支架术，持续8周。术后维持动物12周，每隔2周和4周进行超声和逆行输尿管造影检查新导管。输尿管新组织和未手术对照组的终点分析包括组织学、免疫组化（IHC）、组织形态学评估以及离体收缩/舒张功能评估。所有动物都存活到预定的安乐死，并在8周的支架植入期间在重建的收集系统中表现出轻度肾积水（1-2级），其中一只动物在术后2周出现持续的皮下瘘。到支架植入12周时，80%的猪未植入支架的新导管导致严重的肾积水（4级）和移植部位内部狭窄形成。在60%的猪中，大量支架挤压到输尿管远端也很明显，导致输尿管梗阻。然而，组织学和免疫组化分析显示形成神经支配的血管化新组织，具有a-平滑肌肌动蛋白+和SM22α+平滑肌束以及uroplakin 3A+和泛细胞角蛋白+尿路上皮。新生组织的体外收缩和松弛反应与未手术的对照组相似。BLSF生物材料代表了小管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。
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.