Vascular remodeling of a novel absorbable polymeric conduit by endogenous cells: First results in the ovine systemic circulation

Background Endogenous Tissue Restoration (ETR) is a regenerative approach in which entirely synthetic, absorbable polymeric implants undergo remodeling mediated by endogenous cells without the use of stem cells or other... [ view full abstract ]

Background
Endogenous Tissue Restoration (ETR) is a regenerative approach in which entirely synthetic, absorbable polymeric implants undergo remodeling mediated by endogenous cells without the use of stem cells or other animal-derived products. Following favorable one year results with an ovine pulmonary artery conduit, we evaluated an entirely synthetic vascular graft in the ovine systemic arterial circulation.

Methods
We developed and characterized the structure, mechanical properties and biocompatibility of a fully bioabsorbable polyester based on the self-complementary ureido-pyrimidinone (UPy) quadruple hydrogen-bonding motif. The device was implanted as an interposition graft in the descending aorta of 6 adult sheep for up to 6 months. To compare pulmonary and systemic arterial conditions directly, 3 additional sheep were implanted with both pulmonary and aortic patches for 6 months.

Results
Angiography confirmed extended graft patency in all 9 animals. Vessel diameters were stable for all aortic and pulmonary patches; no aneurysms were noted. In 3 of 6 aortic interposition grafts, an aneurysmal dilatation was observed between 4 and 6 months. Histological examination demonstrated a thicker remodeled vascular wall in the dilated areas. In general, remodeling was qualitatively similar in pulmonary and aortic environments, although the aortic grafts developed a thicker adventitial layer.

Conclusions
This study demonstrates experimental ETR in the systemic arterial circulation in sheep. Although conduit mechanical characteristics will need to be optimized to avoid dilation and/or aneurysms, we demonstrated the potential of a fully synthetic bioabsorbable conduit to guide the restoration of host tissue into a functional living vascular replacement, without exogenous cells.