Algarrahi Khalid, Affas Saif, Sack Bryan S, Yang Xuehui, Costa Kyle, Seager Catherine, Estrada Carlos R, Mauney Joshua R
Urological Diseases Research Center, Boston Children's Hospital, Boston, Massachusetts; Department of Surgery, Harvard Medical School, Boston, Massachusetts.
Urological Diseases Research Center, Boston Children's Hospital, Boston, Massachusetts.
J Surg Res. 2018 Sep;229:192-199. doi: 10.1016/j.jss.2018.04.006. Epub 2018 May 1.
Preclinical validation of scaffold-based technologies in animal models of urethral disease is desired to assess wound healing efficacy in scenarios that mimic the target patient population. This study investigates the feasibility of bilayer silk fibroin (BLSF) scaffolds for the repair of previously damaged urethras in a rabbit model of onlay urethroplasty.
A focal, partial thickness urethral injury was created in adult male rabbits (n = 12) via electrocoagulation and then onlay urethroplasty with 50 mm BLSF grafts was carried out 2 wk after injury. Animals were randomly divided into three experimental groups and harvested at 2 wk after electrocoagulation (n = 3), and 1 (n = 3) or 3 (n = 6) months after scaffold implantation. Outcome analyses were performed preoperatively and at 2 wk after injury in all groups as well as at 1 or 3 mo after scaffold grafting and included urethroscopy, retrograde urethrography (RUG), and histological and immunohistochemical analyses.
At 2 wk after electrocoagulation, urethroscopic and RUG evaluations confirmed urethral stricture formation in 92% (n = 11/12) of rabbits. Gross tissue assessments at 1 (n = 3) and 3 (n = 6) mo after onlay urethroplasty revealed host tissue ingrowth covering the entire implant site. At 3 mo post-op, RUG analyses of repaired urethral segments demonstrated a 39% reduction in urethral stenosis detected following electrocoagulation injury. Histological and immunohistochemical analyses revealed the formation of innervated, vascularized neotissues with α-smooth muscle actin+ and SM22α+ smooth muscle bundles and pan-cytokeratin + epithelium at graft sites.
These results demonstrate the feasibility of BLSF matrices to support the repair of previously damaged urethral tissues.
基于支架的技术在尿道疾病动物模型中的临床前验证，有助于在模拟目标患者群体的情况下评估伤口愈合效果。本研究探讨双层丝素蛋白（BLSF）支架在兔覆盖式尿道成形术模型中修复先前受损尿道的可行性。
通过电凝法在成年雄性兔（n = 12）身上造成局灶性、部分厚度的尿道损伤，损伤后2周进行50毫米BLSF移植物的覆盖式尿道成形术。动物被随机分为三个实验组，分别在电凝后2周（n = 3）、支架植入后1个月（n = 3）或3个月（n = 6）处死。所有组在术前、损伤后2周以及支架植入后1或3个月进行结果分析，包括尿道镜检查、逆行尿道造影（RUG）以及组织学和免疫组织化学分析。
电凝后2周，尿道镜和RUG评估证实92%（n = 11/12）的兔出现尿道狭窄形成。覆盖式尿道成形术后1个月（n = 3）和3个月（n = 6）的大体组织评估显示，宿主组织向内生长覆盖了整个植入部位。术后3个月，对修复尿道段的RUG分析表明，电凝损伤后检测到的尿道狭窄减少了39%。组织学和免疫组织化学分析显示，移植部位形成了有神经支配、血管化的新组织，有α-平滑肌肌动蛋白+和SM22α+平滑肌束以及全细胞角蛋白+上皮。
这些结果证明了BLSF基质支持修复先前受损尿道组织的可行性。
