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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. In addition to restoring blood flow, the engineered HAV demonstrates the capacity for host cellular remodeling into native-like vasculature. Here we report preclinical evaluation of a small-diameter (3.5 mm) HAV as a mBTTs in a non-human primate model. Methods: We implanted 3.5 mm HAVs as right subclavian artery to pulmonary artery mBTTs in non-immunosuppressed juvenile rhesus macaques (n = 5). HAV patency, structure, and blood flow were assessed by postoperative imaging from 1 week to 6 months. Histology of HAVs and surrounding tissues was performed. Results: Surgical procedures were well tolerated, with satisfactory anastomoses, showing feasibility of using the 3.5 mm HAV as a mBTTs. All macaques had some immunological reactivity to the human extracellular matrix, as expected in this xenogeneic model. HAV mBTTs remained patent for up to 6 months in animals, exhibiting mild immunoreactivity. Two macaques displaying more severe immunoreactivity to the human HAV material developed midgraft dilatation without bleeding or rupture. HAV repopulation by host cells expressing smooth muscle and endothelial markers was observed in all animals. Conclusions: These findings may support use of 3.5 mm HAVs as mBTTs in CCHD and potentially other pediatric vascular indications.

Plain language summary Surgery to correct defects in the heart that are present at birth sometimes requires the use of artificial blood vessels called vascular grafts. Tissue-engineered vascular grafts (TEVGs) are scaffolds seeded with cells that can develop into functional blood vessels over time. We conducted a series of laboratory and computer-based experiments to investigate how TEVGs develop into functional blood vessels, and demonstrated two phases of changes to the TEVG after implantation: an early phase driven by inflammation, and a later phase driven by the mechanical properties of the tissue. At later time points, the resulting blood vessels demonstrated the ability to grow and respond to blood flow in similar ways to the body’s own blood vessels. These results provide insight into the processes by which TEVGs become functional blood vessels, with implications for future clinical use of this technology.

Bioabsorbable materials made from polymeric compounds have been used in many fields of regenerative medicine to promote tissue regeneration. These materials replace autologous tissue and, due to their growth potential, make excellent substitutes for cardiovascular applications in the treatment of congenital heart disease. However, there remains a sizable gap between their theoretical advantages and actual clinical application within pediatric cardiovascular surgery. This review will focus on four areas of regenerative medicine in which bioabsorbable materials have the potential to alleviate the burden where current treatment options have been unable to within the field of pediatric cardiovascular surgery. These four areas include tissue-engineered pulmonary valves, tissue-engineered patches, regenerative medicine options for treatment of pulmonary vein stenosis and tissue-engineered vascular grafts. We will discuss the research and development of biocompatible materials reported to date, the evaluation of materials in vitro, and the results of studies that have progressed to clinical trials.

In [2] (Preprint, 2006, arXiv:math.RT/0609363) the authors initiated a study of the representation theory of classical Lie superalgebras via a cohomological approach. Detecting subalgebras were constructed and a theory of support varieties was developed. The dimension of a detecting subalgebra coincides with the defect of the Lie superalgebra, and the dimension of the support variety for a simple supermodule was conjectured to equal the atypicality of the supermodule. In this paper the authors compute the support varieties of Kac supermodules for Type-I Lie superalgebras and of the simple supermodules for (m|n). The latter result verifies our earlier conjecture for (m|n). In our investigation we also delineate several of the major differences between Type-I versus Type-II classical Lie superalgebras. Finally, the connection between atypicality, defect and superdimension is made more precise by using the theory of support varieties and representations of Clifford superalgebras. [ABSTRACT FROM AUTHOR]