Bioengineered Human Arteries for the Repair of Vascular Injuries

JAMA Surg. 2024 Nov 20:e244893. doi: 10.1001/jamasurg.2024.4893. Online ahead of print.

Abstract

Importance: Vascular injuries require urgent repair to minimize loss of limb and life. Standard revascularization relies on autologous vein or synthetic grafts, but alternative options are needed when adequate vein is not feasible and when clinical conditions preclude safe use of synthetic materials.

Objective: To evaluate the performance of the acellular tissue engineered vessel (ATEV) in the repair of arterial injuries.

Design, setting, and participants: Two open-label, single-arm, nonrandomized clinical trials, including 1 prospective civilian study (CLN-PRO-V005 [V005]) and 1 retrospective observational study in a war zone (CLN-PRO-V017 [V017]), were conducted from September 2018 to January 2024 (follow-up ongoing) at 19 level 1 trauma centers in the US and Israel and 5 frontline hospitals in Ukraine. Patients had vascular injury, no autologous vein available for emergent revascularization, and risk factors for wound infection. Data were analyzed from September 2023 to January 2024.

Intervention: The ATEV is a bioengineered vascular conduit grown from human vascular cells, available off the shelf, and implantable without immunosuppression.

Main outcomes and measures: Primary patency at day 30 was the primary outcome. Secondary outcomes included limb salvage, graft infection, and patient survival. A systematic literature review identified synthetic graft benchmarks in the treatment of arterial trauma for the same end points.

Results: The V005 and V017 studies evaluated 69 and 17 patients, respectively, and included 51 in V005 and 16 in V017 with noniatrogenic arterial injuries of the extremities. The majority were male (V005, 38 [74.5%]; V017, 16 [100%]), the mean (SD) ages were similar (V005, 33.5 [13.6] years; V017, 34.2 [9.0] years), and the mean (SD) Injury Severity Scores were similar (V005, 20.8 [10.5]; V017, 20.1 [18.9]). Penetrating injuries dominated (V005, 29 patients [56.9%]; V017, 14 patients [87.5%]). At day 30 for the V005 and V017 trials, respectively, ATEV primary patency was 84.3% (95% CI, 72.0%-91.8%) and 93.8% (95% CI, 71.7%-98.9%); secondary patency was 90.2% (95% CI, 79.0%-95.7%) and 93.8% (95% CI, 71.7%-98.9%); amputation rate was 9.8% (95% CI, 4.3%-21.0%) and 0% (95% CI, 0.0%-19.4%); ATEV infection rate was 2.0% (95% CI, 0.4%-10.3%) and 0% (95% CI, 0.0%-19.4%); and death rate was 5.9% (95% CI, 2.0%-15.9%) and 0% (95% CI, 0.0%-19.4%) (no deaths attributed to the ATEV). Day 30 synthetic graft benchmarks were as follows: secondary patency, 78.9%; amputation, 24.3%; infection, 8.4%; and death, 3.4%.

Conclusions and relevance: Results of 2 single-arm trials in civilian and real-world military settings suggest that the ATEV provides benefits in terms of patency, limb salvage, and infection resistance. Comparing ATEV outcomes with synthetic graft benchmarks demonstrates improved outcomes in the treatment of acute vascular injuries of the extremities.

Trial registration: ClinicalTrials.gov Identifiers: NCT03005418, NCT05873959.

Associated data

  • ClinicalTrials.gov/NCT05873959
  • ClinicalTrials.gov/NCT03005418