Xiao Lu1, Ling Han1, Ghassan S Kassab2. 1. California Medical Innovations Institute, San Diego, CA 92121, USA. 2. California Medical Innovations Institute, San Diego, CA 92121, USA. Electronic address: gkassab@calmi2.org.
Abstract
BACKGROUND: There is a significant clinical need for small vascular grafts <1 mm in diameter. MATERIALS AND METHODS: The structure and composition of swine pulmonary visceral pleura (PVP) were investigated. Two processes, glutaraldehyde (GA) crosslink and decellularization (dc) plus GA crosslink, were used to inhibit the immune response. The thrombosis-resistance of the GA-crosslinked PVP (GA-PVP) was determined with in vitro and in vivo studies. Small vessel grafts with 0.7 diameter mm were constructed using the GA-PVP and surgically interposed in the femoral artery of rats for up to 24 weeks. Blood flow in the GA-PVP grafts were measured and ex vivo vascular reactivity of the prostheses were evaluated along with immuno-histological analysis. RESULTS: The GA-PVP mesothelium contains abundant glycocalyx-like substance and a smooth surface. The mechanical properties of the GA-PVP were similar to the femoral artery of rat in the range of physiological pressures. The in vitro and in vivo studies confirmed poor platelet adhesion on the GA-PVP mesothelial surface in comparison with dc processed PVP (dc-PVP). Patency of the GA-PVP prostheses in femoral arteries of rats was 86% in the 24 weeks postoperative period while patency of dc-PVP in femoral arteries of rats was 33% at 1 week postoperative period. Blood flow in the GA-PVP prostheses were not statistically different than the contralateral femoral artery. Biomarkers of neo-endothelial cells, neo-media smooth muscle cells, and extracellular matrices were observed in the GA-PVP prostheses. The significant agonists-induced vasoconstriction and endothelium-dependent vasodilation were apparent at 12 weeks and further amplified in the 24 weeks postoperative, which suggests self-assembly of functional neo-endothelium and neo-media. CONCLUSIONS: The high patency and functionality of the small grafts suggest that the GA-PVP is a promising prosthetic biomaterial for vascular reconstructions. STATEMENT OF SIGNIFICANCE: Small artery graft (diameter <1 mm) in the peripheral circulation that functionally arterializes has not been possible primarily due to thrombosis. Our findings indicate that lung visceral pleura may address thrombogenicity as the major pitfall in small diameter grafts. Here, grafts of 0.7 mm diameter were constructed from swine pulmonary visceral pleura (PVP) and implanted into femoral artery position of rats up to 24 weeks. The total patency of grafts in femoral arteries of rats was 86% in the 24-week period. The neo-endothelial and -medial layers were assembled in the grafts as evidenced by robust biomarkers of endothelial cells, smooth muscle cells, and extracellular matrices observed in the grafts. Agonists-induced vasoconstriction and endothelium-dependent vasodilation were apparent at 12 weeks and were amplified at 24 weeks. The high patency of the small grafts suggests that the PVP is a promising prosthetic biomaterial for vascular reconstructions.
BACKGROUND: There is a significant clinical need for small vascular grafts <1 mm in diameter. MATERIALS AND METHODS: The structure and composition of swinepulmonary visceral pleura (PVP) were investigated. Two processes, glutaraldehyde (GA) crosslink and decellularization (dc) plus GA crosslink, were used to inhibit the immune response. The thrombosis-resistance of the GA-crosslinked PVP (GA-PVP) was determined with in vitro and in vivo studies. Small vessel grafts with 0.7 diameter mm were constructed using the GA-PVP and surgically interposed in the femoral artery of rats for up to 24 weeks. Blood flow in the GA-PVP grafts were measured and ex vivo vascular reactivity of the prostheses were evaluated along with immuno-histological analysis. RESULTS: The GA-PVP mesothelium contains abundant glycocalyx-like substance and a smooth surface. The mechanical properties of the GA-PVP were similar to the femoral artery of rat in the range of physiological pressures. The in vitro and in vivo studies confirmed poor platelet adhesion on the GA-PVP mesothelial surface in comparison with dc processed PVP (dc-PVP). Patency of the GA-PVP prostheses in femoral arteries of rats was 86% in the 24 weeks postoperative period while patency of dc-PVP in femoral arteries of rats was 33% at 1 week postoperative period. Blood flow in the GA-PVP prostheses were not statistically different than the contralateral femoral artery. Biomarkers of neo-endothelial cells, neo-media smooth muscle cells, and extracellular matrices were observed in the GA-PVP prostheses. The significant agonists-induced vasoconstriction and endothelium-dependent vasodilation were apparent at 12 weeks and further amplified in the 24 weeks postoperative, which suggests self-assembly of functional neo-endothelium and neo-media. CONCLUSIONS: The high patency and functionality of the small grafts suggest that the GA-PVP is a promising prosthetic biomaterial for vascular reconstructions. STATEMENT OF SIGNIFICANCE: Small artery graft (diameter <1 mm) in the peripheral circulation that functionally arterializes has not been possible primarily due to thrombosis. Our findings indicate that lung visceral pleura may address thrombogenicity as the major pitfall in small diameter grafts. Here, grafts of 0.7 mm diameter were constructed from swinepulmonary visceral pleura (PVP) and implanted into femoral artery position of rats up to 24 weeks. The total patency of grafts in femoral arteries of rats was 86% in the 24-week period. The neo-endothelial and -medial layers were assembled in the grafts as evidenced by robust biomarkers of endothelial cells, smooth muscle cells, and extracellular matrices observed in the grafts. Agonists-induced vasoconstriction and endothelium-dependent vasodilation were apparent at 12 weeks and were amplified at 24 weeks. The high patency of the small grafts suggests that the PVP is a promising prosthetic biomaterial for vascular reconstructions.