From the Humacyte, Inc. (R.D.K., H.L.P., L.E.N.), Durham, North Carolina; Department of Surgery (J.D.B.W.), Keesler Medical Center, Biloxi, Massachusetts; Department of Surgery (R.H.), William Beaumont Army Medical Center, El Paso, Texas; Department of Surgery (T.E.R.), Division of Vascular and Endovascular Surgery, Mayo Clinic, Rochester, Minnesota.
J Trauma Acute Care Surg. 2023 Aug 1;95(2):234-241. doi: 10.1097/TA.0000000000003974. Epub 2023 Mar 22.
This study evaluated performance of a tissue-engineered human acellular vessel (HAV) in a porcine model of acute vascular injury and ischemia. The HAV is an engineered blood vessel consisted of human vascular extracellular matrix proteins. Limb reperfusion and vascular outcomes of the HAV were compared with those from synthetic expanded polytetrafluoroethylene (ePTFE) grafts.
Thirty-six pigs were randomly assigned to four treatment groups, receiving either the HAV or a PTFE graft following a hind limb ischemia period of either 0 or 6 hours. All grafts were 3-cm-long interposition 6-mm diameter grafts implanted within the right iliac artery. Animals were not immunosuppressed and followed for up to 28 days after surgery. Assessments performed preoperatively and postoperatively included evaluation of graft patency, hind limb function, and biochemical markers of tissue ischemia or reperfusion injury. Histological analysis was performed on explants to assess host cell responses.
Postoperative gait assessment and biochemical analysis confirmed that ischemia and reperfusion injury were caused by 6-hour ischemia, regardless of vascular graft type. Hind limb function and tissue damage biomarkers improved in all groups postoperatively. Final patency rates at postoperative day 28 were higher for HAV than for ePTFE graft in both the 0-hour (HAV, 85.7%; ePTFE, 66.7%) and 6-hour (HAV, 100%; ePTFE, 75%) ischemia groups, but these differences were not statistically significant. Histological analyses identified some intimal hyperplasia and host reactivity to the xenogeneic HAV and also to the synthetic ePTFE graft. Positive host integration and vascular cell infiltration were identified in HAV but not ePTFE explants.
Based on the functional performance and the histologic profile of explanted HAVs, this study supports further investigation to evaluate long-term performance of the HAV when used to repair traumatic vascular injuries.
本研究评估了组织工程化人去细胞血管(HAV)在猪急性血管损伤和缺血模型中的性能。HAV 是一种由人血管细胞外基质蛋白组成的工程化血管。比较了 HAV 与合成的膨体聚四氟乙烯(ePTFE)移植物的肢体再灌注和血管结局。
36 头猪随机分为 4 个治疗组,在下肢缺血 0 或 6 小时后分别接受 HAV 或 ePTFE 移植物。所有移植物均为 3cm 长、6mm 直径的移植物,植入右侧髂动脉内。动物未进行免疫抑制治疗,术后随访长达 28 天。术前和术后评估包括移植物通畅性、下肢功能和组织缺血或再灌注损伤的生化标志物。对标本进行组织学分析,以评估宿主细胞反应。
术后步态评估和生化分析证实,6 小时缺血会导致缺血再灌注损伤,与血管移植物类型无关。所有组术后下肢功能和组织损伤生物标志物均改善。术后 28 天,0 小时(HAV,85.7%;ePTFE,66.7%)和 6 小时(HAV,100%;ePTFE,75%)缺血组 HAV 的最终通畅率均高于 ePTFE 移植物,但差异无统计学意义。组织学分析发现,异种 HAV 和合成 ePTFE 移植物均存在一定的内膜增生和宿主反应。在 HAV 但不在 ePTFE 标本中发现了阳性的宿主整合和血管细胞浸润。
基于 HAV 移植后的功能表现和组织学特征,本研究支持进一步研究,以评估 HAV 在修复创伤性血管损伤时的长期性能。