Evaluating the Safety and Efficacy of Humacyte Acellular Tissue-Engineered Vessel in a Real-World Combat Setting: A Retrospective Observational Multicenter Study.

Abstract

Introduction: Peripheral vascular trauma occurs as 10% of trauma injuries in combat settings. Its treatment in a combat setting is associated with challenges such as increased risk of infection, increased time to treatment, and lack of availability of medical personnel to perform vascular surgery. Currently, the autologous great saphenous vein or synthetic vessels such as Dacron or Gore-Tex (Teflon) are used to treat peripheral vascular trauma. Unfortunately, these options may neither be available nor advisable because of injury to the native vasculature or the increased risk of infection. Thus, an unmet medical need exists for peripheral vascular trauma among wounded military personnel. An alternative for autologous vein or synthetic vessel grafts mechanically similar to native vasculature and with increased infection resistance compared to synthetic alternatives is needed.

Materials and methods: This multicenter, retrospective, observational study examines the use of the acellular tissue-engineered vessel (ATEV) for the treatment of peripheral vascular trauma in a combat setting in Ukraine. The ATEV is an acellular engineered human artery, manufactured from human vascular cells and then decellularized, generating an off-the-shelf conduit that can be immediately available for treatment of arterial injuries. A 1-year Humanitarian effort spanning from June 2022 to May 2023 treated a total of 19 patients suffering extremity arterial injuries with the ATEV in Ukraine. Retrospective data were collected for efficacy and safety outcomes in 17 of these patients, of whom 14 suffered battlefield injuries including gunshots, blast, and shrapnel-related trauma. The primary objectives were to evaluate the safety and efficacy of the Humacyte ATEVs that were implanted for arterial replacement or reconstruction in patients sustaining vascular trauma, and to determine the 30-day rate of primary ATEV patency. The secondary objectives were to determine the rates of ATEV infection, amputation, mortality, and adverse events of special interest related to the ATEV, to assess ATEV durability, and to determine the 30-day limb salvage, infection free time, and patency of the human acellular vessel regardless of interventions. The hypothesis was that ATEVs would achieve similar patency, infection-free rate, limb salvage, and safety outcomes as current standards of care.

Results: After up to 18 total months of data collection in 17 subjects, ATEVs patency was 87.1% (95% CI, 42.5-97.8) up to 18 months. The infection-free rate for the ATEV conduits was 100%. Limb salvage and survival rates were also 100% up to 18 months. Overall, ATEV grafts were well tolerated, with no instances of immunological rejection. In two subjects, the ATEV was abandoned: in one case because of thrombosis, and in the other because of damage to the ATEV caused by remaining shrapnel.

Conclusions: ATEV functioned as intended in the treatment of acute and combat-related vascular injuries. Conduit infection rate and amputations of the treated limbs were zero. Patency rates were acceptable, and losses of patency did not lead to loss of the treated limb. This study characterizes the first of its kind, cell-derived biologic engineered artery for use in civilian and military personnel who are injured during combat.