Preliminary Experience With the Human Acellular Vessel: A Descriptive Case Series Detailing Early Use of a Bioengineered Blood Vessel for Arterial Repair
“…This trend is similar for animal-derived xenografts implanted for arterial repair in that bovine artery (Artegraft; LeMaitre Vascular, Burlington, MA) has higher patency rates 28 than bovine vein (ProCol, LeMaitre Vascular, Burlington, MA), which is also prone to aneurysmal failure under higher-pressure arterial blood flow 29 . Tissue-engineered HAV may provide the off-the-shelf convenience and consistency of synthetic grafts, but with the biocompatibility, infection resistance, and mechanical strength of native blood vessels 11,13,17 …”
Section: Discussionmentioning
confidence: 79%
“…29 Tissue-engineered HAV may provide the offthe-shelf convenience and consistency of synthetic grafts, but with the biocompatibility, infection resistance, and mechanical strength of native blood vessels. 11,13,17 In this study, a porcine model was used to evaluate the impact of ischemia time and implanted conduit material (HAV or ePTFE) on graft patency, recovery of limb function, and host cellular response following arterial reconstruction. Postoperative impairment of hind limb motor function and spiked elevation of biomarkers for muscle damage 19,30 confirmed successful induction of neuromuscular injury when 6 hours of ischemia preceded vascular reperfusion with either material.…”
Section: Discussionmentioning
confidence: 99%
“…To date, the HAV has been implanted in more than 500 patients within expanded access cases 12,13 and clinical trials 14,15 including an ongoing trial for the repair of vascular trauma (ClinicalTrials.gov identifier, NCT03005418). These studies have demonstrated the potential of the HAV for durability and patency, 16 adaptive host recellularization and remodeling, 17 and resistance to infection, including within environments with high infection risk such as vascular access for dialysis 14 and vascular trauma 13 as well as after replacement of a contaminated synthetic graft. 18 The objective of this study was to evaluate patency and function of the investigational bioengineered HAV, as compared with a commercially available synthetic ePTFE graft, when used for vascular repair in a large animal model of hind limb ischemia and reperfusion injury.…”
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
“…This trend is similar for animal-derived xenografts implanted for arterial repair in that bovine artery (Artegraft; LeMaitre Vascular, Burlington, MA) has higher patency rates 28 than bovine vein (ProCol, LeMaitre Vascular, Burlington, MA), which is also prone to aneurysmal failure under higher-pressure arterial blood flow 29 . Tissue-engineered HAV may provide the off-the-shelf convenience and consistency of synthetic grafts, but with the biocompatibility, infection resistance, and mechanical strength of native blood vessels 11,13,17 …”
Section: Discussionmentioning
confidence: 79%
“…29 Tissue-engineered HAV may provide the offthe-shelf convenience and consistency of synthetic grafts, but with the biocompatibility, infection resistance, and mechanical strength of native blood vessels. 11,13,17 In this study, a porcine model was used to evaluate the impact of ischemia time and implanted conduit material (HAV or ePTFE) on graft patency, recovery of limb function, and host cellular response following arterial reconstruction. Postoperative impairment of hind limb motor function and spiked elevation of biomarkers for muscle damage 19,30 confirmed successful induction of neuromuscular injury when 6 hours of ischemia preceded vascular reperfusion with either material.…”
Section: Discussionmentioning
confidence: 99%
“…To date, the HAV has been implanted in more than 500 patients within expanded access cases 12,13 and clinical trials 14,15 including an ongoing trial for the repair of vascular trauma (ClinicalTrials.gov identifier, NCT03005418). These studies have demonstrated the potential of the HAV for durability and patency, 16 adaptive host recellularization and remodeling, 17 and resistance to infection, including within environments with high infection risk such as vascular access for dialysis 14 and vascular trauma 13 as well as after replacement of a contaminated synthetic graft. 18 The objective of this study was to evaluate patency and function of the investigational bioengineered HAV, as compared with a commercially available synthetic ePTFE graft, when used for vascular repair in a large animal model of hind limb ischemia and reperfusion injury.…”
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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.
“…[6] It is in this range that TE macrovessels have been mostly proposed, making use of, for example, biodegradable scaffolding materials to harbor cells that produce robust ECM during a long maturation process, followed by decellularization to yield constructs capable of being used off-the-shelf. Preliminary clinical outcomes are highly encouraging, [7,8] suggesting a viable route to engineer functional vessels at this scale. However, the long and complex biofabrication processes and/or thrombogenicity concerns derived from the use of synthetic materials may complicate widespread clinical adoption.…”
Vascularization is a key issue for the clinical translation of tissue engineering strategies. This has been recognized in the field for almost two decades. Several strategies to solve this issue are proposed but none has decisively tackled the problem. This is in part due to an excessive focus on microvascularization that ignores the need of having macrovessels capable of being surgically connected to the patient's circulation upon implantation. Indeed, a strategy for macrovessel engineering must co‐exist with a strategy for microvessels. And if this is true, all the intermediate scales have to be addressed as well. Therefore, multiscale vascular networks must be the focus of tissue engineering vascularization efforts. In this work, a reflection is made on a possible path forward for researchers and engineers in the field to achieve the ultimate goal of efficient vascularization of engineered tissues and organs.
“…Developing an optimal reconstructive plan for complex situations requires patient-specific approaches that can be aided by new endovascular and regenerative medicine technologies to optimize long-term outcomes. 1 , 2 , 3 …”
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