Pilot assessment of a human extracellular matrix-based vascular graft in a rabbit model

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Abstract

Background:

Herein we describe a small-diameter vascular graft constructed from rolled human amniotic membrane (hAM), with in vitro evaluation and subsequent in vivo assessment of its mechanical and initial biologic viability in the early postimplantation period. This approach for graft construction allows customization of graft dimensions, with wide-ranging potential clinical applicability as a nonautologous, allogeneic, cell-free graft material.

Methods:

Acellular hAMs were rolled into layered conduits (3.2-mm diameter) that were bound with fibrin and lyophilized. Constructs were seeded with human smooth muscle cells and cultured under controlled arterial hemodynamic conditions in vitro. Additionally, the acellular hAM conduits were surgically implanted as arterial interposition grafts into the carotid arteries of immunocompetent rabbits.

Results:

On in vitro analysis, smooth muscle cells were shown to adhere to, proliferate within, and remodel the scaffold during a 4-week culture period. At the end of the culture period, there was histologic and biomechanical evidence of graft wall layer coalescence. In vivo analysis demonstrated graft patency after 4 weeks (n = 3), with no hyperacute rejection or thrombotic occlusion. Explants displayed histologic evidence of active cellular remodeling, with endogenous cell repopulation of the graft wall concurrent with degradation of initial graft material. Cells were shown to align circumferentially to resemble a vascular medial layer.

Conclusions:

The vascular grafts were shown to provide a supportive scaffold allowing cellular infiltration and remodeling by host cell populations in vivo. By use of this approach, “off-the-shelf” vascular grafts can be created with specified diameters and wall thicknesses to satisfy specific anatomic requirements in diverse populations of patients.

Clinical Relevance:

This preliminary study introduces the use of an allogeneic, cell-free, small-diameter vascular graft derived from the rolled human amniotic membrane. With this approach, graft diameter and wall thickness can be modulated to create conduits of specified dimensions. The ultimate goal is for the graft to integrate with native vasculature, allowing subsequent growth potential. Future work is needed to evaluate long-term remodeling and viability; however, in vivo investigation provides evidence that the layered scaffold can both mechanically withstand the stress of surgical implantation into native vasculature and subsequently support infiltration and early remodeling by host cell populations during 4 weeks.

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