Off-the-shelf, heparinized small diameter vascular graft limits acute thrombogenicity in a porcine model.

Thrombogenicity poses a challenge to the clinical translation of engineered grafts. Previously, small-diameter vascular grafts (sdVG) composed of fibrin hydrogel microfiber tubes (FMT) with an external poly(ε-caprolactone) (PCL) sheath supported long-term patency in mice. Towards the development of an sdVG with off-the-shelf availability, the FMT's shelf stability, scale-up, and successful conjugation of an antithrombotic drug to the fibrin scaffold are reported here.

gain-of-function mutation modulates the stiffness of smooth muscle cells and compromises vascular mechanics.

Heterozygous gain-of-function (GOF) mutations of hypoxia-inducible factor 2α (HIF2A), a key hypoxia-sensing regulator, are associated with erythrocytosis, thrombosis, and vascular complications that account for morbidity and mortality of patients. We demonstrated that the vascular pathology of HIF2A GOF mutations is independent of erythrocytosis. We generated HIF2A GOF-induced pluripotent stem cells (iPSCs) and differentiated them into endothelial cells (ECs) and smooth muscle cells (SMCs).

Regenerative and durable small-diameter graft as an arterial conduit.

Despite significant research efforts, clinical practice for arterial bypass surgery has been stagnant, and engineered grafts continue to face postimplantation challenges. Here, we describe the development and application of a durable small-diameter vascular graft with tailored regenerative capacity. We fabricated small-diameter vascular grafts by electrospinning fibrin tubes and poly(ε-caprolactone) fibrous sheaths, which improved suture retention strength and enabled long-term survival.

Human Pluripotent Stem Cells to Engineer Blood Vessels.

Development of pluripotent stem cells (PSCs) is a remarkable scientific advancement that allows scientists to harness the power of regenerative medicine for potential treatment of disease using unaffected cells. PSCs provide a unique opportunity to study and combat cardiovascular diseases, which continue to claim the lives of thousands each day. Here, we discuss the differentiation of PSCs into vascular cells, investigation of the functional capabilities of the derived cells, and their utilization to engineer microvascular beds or vascular grafts for clinical application.

Three-dimensional culture of small-diameter vascular grafts.

In this review we analyze a representative sample of efforts to engineer three dimensional small-diameter (<6 mm) vascular grafts, concentrating on biomaterial substrates, cellular choices, and biomechanical stimulation. Natural or synthetic scaffolds for vascular engineering need to mimic the natural extracellular matrix microenvironment, maintain physiological mechanical properties, be biocompatible and cell adhesive, and control cellular structure and function. Additionally, multicellular culture with stem cells that are highly proliferative and differentiable should be used to better recapitulate native vasculature.