Evaluation of tissue-engineered human acellular vessels as a Blalock-Taussig-Thomas shunt in a juvenile primate model.

Objectives: Palliative treatment of cyanotic congenital heart disease (CCHD) uses systemic-to-pulmonary conduits, often a modified Blalock-Taussig-Thomas shunt (mBTTs). Expanded polytetrafluoroethylene (ePTFE) mBTTs have associated risks for thrombosis and infection. The Human Acellular Vessel (HAV) (Humacyte, Inc) is a decellularized tissue-engineered blood vessel currently in clinical trials in adults for vascular trauma, peripheral artery disease, and end-stage renal disease requiring hemodialysis.

Biological mechanisms of infection resistance in tissue engineered blood vessels compared to synthetic expanded polytetrafluoroethylene grafts.

Objective: Synthetic expanded polytetrafluoroethylene (ePTFE) grafts are known to be susceptible to bacterial infection. Results from preclinical and clinical studies of bioengineered human acellular vessels (HAVs) have shown relatively low rates of infection. This study evaluates the interactions of human neutrophils and bacteria with ePTFE and HAV vascular conduits to determine whether there is a correlation between neutrophil-conduit interactions and observed differences of their infectivity in vivo.

Evaluation of vascular repair by tissue-engineered human acellular vessels or expanded polytetrafluoroethylene grafts in a porcine model of limb ischemia and reperfusion.

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.

Six-year outcomes of a phase II study of human-tissue engineered blood vessels for peripheral arterial bypass.

Objective: The human acellular vessel (HAV) was evaluated for surgical bypass in a phase II study. The primary results at 24 months after implantation have been reported, and the patients will be evaluated for ≤10 years.

Methods: In the present report, we have described the 6-year results of a prospective, open-label, single-treatment arm, multicenter study.

Arterial reconstruction with human bioengineered acellular blood vessels in patients with peripheral arterial disease.

Objective: Vascular conduit is essential for arterial reconstruction for a number of conditions, including trauma and atherosclerotic occlusive disease. We have developed a tissue-engineered human acellular vessel (HAV) that can be manufactured, stored on site at hospitals, and be immediately available for arterial vascular reconstruction. Although the HAV is acellular when implanted, extensive preclinical and clinical testing has demonstrated that the HAV subsequently repopulates with the recipient's own vascular cells.

Bioengineered human acellular vessels recellularize and evolve into living blood vessels after human implantation.

Traditional vascular grafts constructed from synthetic polymers or cadaveric human or animal tissues support the clinical need for readily available blood vessels, but often come with associated risks. Histopathological evaluation of these materials has shown adverse host cellular reactions and/or mechanical degradation due to insufficient or inappropriate matrix remodeling. We developed an investigational bioengineered human acellular vessel (HAV), which is currently being studied as a hemodialysis conduit in patients with end-stage renal disease.

Susceptibility of ePTFE vascular grafts and bioengineered human acellular vessels to infection.

Background: Synthetic expanded polytetrafluorethylene (ePTFE) grafts are routinely used for vascular repair and reconstruction but prone to sustained bacterial infections. Investigational bioengineered human acellular vessels (HAVs) have shown clinical success and may confer lower susceptibility to infection. Here we directly compared the susceptibility of ePTFE grafts and HAV to bacterial contamination in a preclinical model of infection.

Bioengineered human acellular vessels for dialysis access in patients with end-stage renal disease: two phase 2 single-arm trials.

Background: For patients with end-stage renal disease who are not candidates for fistula, dialysis access grafts are the best option for chronic haemodialysis. However, polytetrafluoroethylene arteriovenous grafts are prone to thrombosis, infection, and intimal hyperplasia at the venous anastomosis. We developed and tested a bioengineered human acellular vessel as a potential solution to these limitations in dialysis access.

An early study on the mechanisms that allow tissue-engineered vascular grafts to resist intimal hyperplasia.

Intimal hyperplasia is one of the prominent failure mechanisms for arteriovenous fistulas and arteriovenous access grafts. Human tissue-engineered vascular grafts (TEVGs) were implanted as arteriovenous grafts in a novel baboon model. Ultrasound was used to monitor flow rates and vascular diameters throughout the study.

Readily available tissue-engineered vascular grafts.

Autologous or synthetic vascular grafts are used routinely for providing access in hemodialysis or for arterial bypass in patients with cardiovascular disease. However, some patients either lack suitable autologous tissue or cannot receive synthetic grafts. Such patients could benefit from a vascular graft produced by tissue engineering.

Bioluminescence imaging of glucose in tissue surrounding polyurethane and glucose sensor implants.

Background: The bioluminescence technique was used to quantify the local glucose concentration in the tissue surrounding subcutaneously implanted polyurethane material and surrounding glucose sensors. In addition, some implants were coated with a single layer of adipose-derived stromal cells (ASCs) because these cells improve the wound-healing response around biomaterials.

Methods: Control and ASC-coated implants were implanted subcutaneously in rats for 1 or 8 weeks (polyurethane) or for 1 week only (glucose sensors).

IFATS collection: Adipose-derived stromal cells improve the foreign body response.

Many implanted devices fail due to the formation of an avascular capsule surrounding the device. Additionally, fat has long been known to promote healing and vascularization. The goals of this study were to identify potential mechanisms of the provascular actions of adipose-derived stromal cells (ASCs) and to improve implant biocompatibility.

Reduced foreign body response at nitric oxide-releasing subcutaneous implants.

The tissue response to nitric oxide (NO)-releasing subcutaneous implants is presented. Model implants were created by coating silicone elastomer with diazeniumdiolate-modified xerogel polymers capable of releasing NO. The host tissue response to such implants was evaluated at 1, 3, and 6 weeks and compared to that of uncoated silicone elastomer blanks and xerogel-coated controls incapable of releasing NO.

Combined bone allograft and adipose-derived stem cell autograft in a rabbit model.

Currently available options for the repair of bony defects have substantial limitations. Much work has looked to the possibility of engineering bone using stem cells. These tissue-engineering efforts have focused on calvarial defect models, which have the advantages of minimal load-bearing and a large surface area.

Adult adipose-derived stem cell attachment to biomaterials.

Attachment of adipose-derived stem cells (ASCs) to biomaterials prior to implantation is a possible strategy for mediating inflammation and wound healing. In this study, the ASC percent coverage was measured on common medical grade biosensor materials subjected to different surface treatments. Cell coverage on silicone elastomer (poly-dimethylsiloxane) was below 20% for all surface treatments.

Inhibition of implant-associated infections via nitric oxide release.

The in vivo antibacterial activity of nitric oxide (NO)-releasing xerogel coatings was evaluated against an aggressive subcutaneous Staphylococcus aureus infection in a rat model. The NO-releasing implants were created by coating a medical-grade silicone elastomer with a sol-gel-derived (xerogel) film capable of storing NO. Four of the bare or xerogel-coated silicone materials were subcutaneously implanted into male rats.