Implantation of Completely Biological Engineered Grafts Following Decellularization into the Sheep Femoral Artery

Abstract

The performance of completely biological, decellularized engineered allografts in a sheep model was evaluated to establish clinical potential of these unique arterial allografts. The 4-mm-diameter, 2-3-cm-long grafts were fabricated from fibrin gel remodeled into an aligned tissue tube in vitro by ovine dermal fibroblasts. Decellularization and subsequent storage had little effect on graft properties, with burst pressure exceeding 4000 mmHg and the same compliance as the ovine femoral artery. Grafts were implanted interpositionally in the femoral artery of six sheep (n = 9), with contralateral sham controls (n = 3). At 8 weeks (n = 5) and 24 weeks (n = 4), all grafts were patent and showed no evidence of dilatation or mineralization. Mid-graft lumen diameter was unchanged. Extensive recellularization occurred, with most cells expressing aSMA. Endothelialization was complete by 24 weeks with elastin deposition evident. These completely biological grafts possessed circumferential alignment/mechanical anisotropy characteristic of native arteries and were cultured only 5 weeks prior to decellularization and storage as ''off-the-shelf'' grafts.

Cellular Self-Assembly with Microsphere Incorporation for Growth Factor Delivery Within Engineered Vascular Tissue Rings

“…[1][2][3][4] In addition to meeting the need for transplantable grafts, functional vascular constructs could also serve as in vitro models to screen potential therapies. 5,6 There are a variety of approaches currently used for the development of tissue-engineered blood vessels, including the use of cell-seeded degradable synthetic polymer scaffolds 2,3,7 and hydrogels, 8,9 as well as scaffold-free cellular self-assembly strategies. 1,4,10,11 Our laboratory developed a cellular self-assembly system to fabricate living engineered human vascular tissue constructs entirely from smooth muscle cells (SMCs).…”

Emerging Trends in Heart Valve Engineering: Part I. Solutions for Future

“…In the context of VIC biology, TGF-b1 and cyclic strain synergistically act to enhance VIC myofibroblast differentiation and collagen synthesis. 66,69,96 VIC response to cyclic strain is ECM protein-dependent, 69 similar to the MSC response to ECM elasticity. 26 To develop a means of delivering customized combinations of microenvironmental cues to the cells within a TEHV, there is growing interest in the use of scaffolds based on synthetic hydrogel materials.…”

“…This matrix exhibited favorable remodeling, including host cell recellularization and spontaneous endothelialization, once implanted into the sheep femoral artery as an interpositional vascular graft. 96 It thus presents potential for tissue durability without the need for anti-coagulation therapy. Further studies are underway to assess this potential.…”

Biological Analogs of Infrainguinal Arteries: Evolution and Development Prospects (Review)

“…The [75,76]; however, their regenerative potential is limited, and their usage is impeded, since it is difficult to match an appropriate tissue, which can be incised for further work with cells [77][78][79].…”