Vascularized in vitro perfusion devices, methods of fabricating, and applications thereof
First Claim
1. A vascularized in vitro perfusion device comprising an adaptable microcirculation, said device comprising:
- a supporting structure comprising a gel matrix,a fabricated network of microfluidic endothelial cell-lined channels, said fabricated network comprising an inlet channel, an outlet channel, and at least one cross channel connecting the inlet channel to the outlet channel, said cross channel positioned at least partially within the gel matrix,an inlet port in fluid communication with the fabricated network, and an outlet port in fluid communication with the fabricated network, anda neovasculature, said neovasculature being derived from intact native microvessels incorporated into the gel matrix and subject to maturing conditions comprising endothelial sprouting and an inosculation between at least two endothelial sprouts respectively derived from the at least one cross channel of the fabricated network and the neovasculature to form a lumen connection therebetween, said neovasculature thus in lumen continuity with said at least one cross channel through the inosculation,wherein the fabricated network is in vascular communication and lumen continuity with the neovasculature to form an adaptable microcirculation.
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Abstract
A bona fide adaptable in vitro microcirculation model is provided by integrating a 3-D printed network of endothelial-cell lined perfusion channels, formed via sacrificial casting in a gel matrix, with a native, adaptable microvasculature matured from native microvessels added to the gel matrix. Responsive vascular adaptation exhibited by the in vitro microcirculation is physiologically relevant. Methods for fabricating, devices, models and investigative platforms for pharmaceutical applications, vascular mechanism and microvessel-parenchyma interaction studies, and vascularizing strategies for tissue engineering applications are also disclosed.
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Citations
20 Claims
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1. A vascularized in vitro perfusion device comprising an adaptable microcirculation, said device comprising:
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a supporting structure comprising a gel matrix, a fabricated network of microfluidic endothelial cell-lined channels, said fabricated network comprising an inlet channel, an outlet channel, and at least one cross channel connecting the inlet channel to the outlet channel, said cross channel positioned at least partially within the gel matrix, an inlet port in fluid communication with the fabricated network, and an outlet port in fluid communication with the fabricated network, and a neovasculature, said neovasculature being derived from intact native microvessels incorporated into the gel matrix and subject to maturing conditions comprising endothelial sprouting and an inosculation between at least two endothelial sprouts respectively derived from the at least one cross channel of the fabricated network and the neovasculature to form a lumen connection therebetween, said neovasculature thus in lumen continuity with said at least one cross channel through the inosculation, wherein the fabricated network is in vascular communication and lumen continuity with the neovasculature to form an adaptable microcirculation. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20)
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Specification