Tissue engineering of intact arterial segments by directed remodeling

Traditional approaches of generating tissue-engineered arteries in vitro rely on expansion of cells in culture to seed onto appropriate scaffolds. We propose that small autologous arteries, not the cells derived from them, may be an attractive starting point for engineered arteries. This approach capitalizes on the ability of intact arteries to grow and remodel in response to chronic changes in their mechanical environment. Carotid arteries from juvenile (∼30-kg) pigs were stretched longitudinally in an ex vivo perfusion system over 9 days. This resulted in a ∼40% increase in artery length at physiological longitudinal stress and a 20 ± 3% increase when unstressed. In contrast, control arteries perfused for 9 days at their physiological loaded length saw no unstressed length increase. Control and elongated arteries displayed native appearance (macroscopic and histological), excellent viability (cellularity and mitochondrial activity), normal vasoactivity, and similar mechanical properties (ultimate stress and ultimate strain) as compared to freshly harvested arteries. Growth, as opposed to just redistribution of existing mass, contributed to elongation as evidenced by an increase in artery weight. Elongated arteries also maintained similar wall thickness as fresh arteries, whereas control arteries decreased significantly.