Evaluation of Bi-Layer Silk Fibroin Grafts for Tubular Ureteroplasty in a Porcine Defect Model

Frontiers in Bioengineering and Biotechnology

Joshua R. Mauney¹  Vivian Cristofaro²  Maryrose P. Sullivan²  Zhamshid Okhunov³  Gokhan Gundogdu³  Hazem Orabi³  Faith Veneri³  Stephanie Starek³  Pengbo Jiang³ 

[1] Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, United States;Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States;Department of Urology, University of California, Irvine, Irvine, CA, United States;Division of Urology, Veterans Affairs Boston Healthcare System, Boston, MA, United States;

关键词: biomaterials;    silk fibroin;    tissue engineering;    ureter;    scaffold;   

DOI  :  10.3389/fbioe.2021.723559

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown