Tissue engineered scaffolds, instrumented bioreactors and methods of use thereof
Systems and methods are provided including a housing configured to receive and engage a hollow tissue structure within a fluid chamber of the housing. A first pair of flow channels and a second pair of flow channels of the housing are fluidly coupled to the fluid chamber. The housing fluidly couples the first pair of flow channels and fluidly couples the second pair of flow channels via a second flow path such that a change in a fluid pressure differential between a first fluid in the first flow path and a second fluid in the second flow path deflects at least a portion of the hollow tissue structure causing a change in flow of the first fluid through the first pair of flow channels or a change in flow of the second fluid through the second pair of flow channels.
1 . A system, comprising:
a housing comprising:
a cavity housing component defining a cavity extending from an opening in a first surface of the cavity housing component; and
a support housing component having a sealing surface configured to sealingly engage the first surface of the cavity housing component thereby sealing the opening and defining a fluid chamber having a sealing end defined by the support housing component,
the support housing component defining a pair of intra-hollow tissue structure flow channels connected to the sealing end of the fluid chamber,
the support housing component including a support ring configured to engage and support an open end of a hollow tissue structure at the sealing end of the fluid chamber with the hollow tissue structure suspended in the fluid chamber and supported only at the support ring, the hollow tissue structure having only one open end, and
the support housing component configured to fluidly couple the pair of intra-hollow tissue structure flow channels with each other and with an interior of the hollow tissue structure via an intra-hollow tissue structure flow path at the sealing end of the fluid chamber;
the housing defining a pair of extra-hollow tissue structure flow channels fluidly coupled to the fluid chamber, at least one of the pair of extra-hollow tissue structure flow channels defined by the cavity housing component, and
the housing configured to receive the hollow tissue structure within the fluid chamber with the hollow tissue structure engaged and supported by the support ring at the sealing end of the fluid chamber to fluidly couple the pair of extra-hollow tissue structure flow channels via an extra-hollow tissue structure flow path extending between an exterior of the hollow tissue structure and a surface of the fluid chamber at least partially surrounding the hollow tissue structure.
2 . The system of claim 1 , further comprising the hollow tissue structure disposed in the fluid chamber and fluidly coupling the pair of intra-hollow tissue structure flow channels together.
3 . The system of claim 2 , wherein the hollow tissue structure comprises a population of cells.
4 . The system of claim 3 , wherein the hollow tissue structure comprising the population of cells is a natural hollow tissue structure or an engineered hollow tissue structure.
5 . The system of claim 4 , wherein the natural hollow tissue structure or the engineered hollow tissue structure is a ventricle, a heart, a stomach, an intestine, a uterus, or a bladder.
6 . The system of claim 2 , wherein the hollow tissue structure is at least partially coated with a sealant.
7 . The system of claim 2 , wherein the hollow tissue structure is fabricated by:
forming micron, submicron or nanometer dimension polymeric fibers, the polymeric fibers configured in a shape of the hollow tissue structure; and
seeding cells onto the polymeric fibers.
8 . The system of claim 2 , wherein the housing and hollow tissue structure form a bioreactor.
9 . The system of claim 1 , further comprising at least one valve associated with at least one of the pair of intra-hollow tissue structure flow channels for controlling fluid flow through at least one of the intra-hollow tissue structure flow path and the extra-hollow tissue structure flow path.
10 . The system of claim 1 , further comprising a first fluid source fluidly coupled to the pair of intra-hollow tissue structure flow channels for supplying a first fluid and a second fluid source fluidly coupled to the pair of extra-hollow tissue structure flow channels for supplying a second fluid.
11 . The system of claim 1 , further comprising a sensor at least partly disposed in the intra-hollow tissue structure flow path or fluidly coupled with the intra-hollow tissue structure flow path.
12 . The system of claim 1 , wherein the pair of intra-hollow tissue structure flow channels converge at the support ring.
13 . The system of claim 1 , wherein the hollow tissue structure is a ventricular hollow tissue structure.
14 . The system of claim 1 , wherein the support housing component includes:
a middle housing component having a mating surface, the sealing surface of the support housing component being a surface of the middle housing component opposite the mating surface, the middle housing component defining a first section of each of the pair of intra-hollow tissue structure flow channels; and
an outer housing component having a complementary mating surface to the mating surface of the middle housing component, the outer housing component defining a second section of each of the pair of intra-hollow tissue structure flow channels;
for each of the pair of intra-hollow tissue structure flow channels, the mating surface of the middle housing component and the complementary mating surface of the outer housing component each configured to hold a valve between the first section of the intra-hollow tissue structure flow channel and the second section of the intra-hollow tissue structure flow channel.
15 . The system of claim 1 , wherein an outer wall of the hollow tissue structure separates the intra-hollow tissue structure flow path and the extra-hollow tissue structure flow path in the fluid chamber.
16 . The system of claim 1 , where in the system is configured such that a change in a fluid pressure differential between a first fluid in the intra-hollow tissue structure flow path and a second fluid in the extra-hollow tissue structure flow path deflects at least a portion of the hollow tissue structure causing a change in flow of the first fluid through the pair of intra-hollow tissue structure flow channels.
17 . A method of forming the system according to claim 1 , the method comprising: attaching the hollow tissue structure to the support ring of the support housing component of the system;
sealingly engaging the support housing component with the cavity housing component thereby fluidly coupling the pair of intra-hollow tissue structure flow channels via the intra-hollow tissue structure flow path into the fluid chamber, through an interior of the hollow tissue structure, and out of the fluid chamber, and
fluidly coupling the pair of extra-hollow tissue structure flow channels via the extra-hollow tissue structure flow path extending between an exterior of the hollow tissue structure and a surface of the fluid chamber.
18 . A method for identifying a compound that modulates a hollow tissue function, comprising:
providing the system of claim 1 ;
contacting the hollow tissue structure with a test compound; and
determining the effect of the test compound on the hollow tissue function in the presence and absence of the test compound, wherein a modulation of the hollow tissue function in the presence of the test compound as compared to the hollow tissue function in the absence of the test compound indicates that the test compound modulates the hollow tissue function, thereby identifying the compound that modulates a hollow tissue function.
19 . A method for identifying a compound useful for treating or preventing a hollow tissue disease, comprising:
providing the system of claim 1 ;
contacting the hollow tissue structure with a test compound; and
determining the effect of the test compound on a hollow tissue function in the presence and absence of the test compound, wherein a modulation of the hollow tissue function in the presence of the test compound as compared to the hollow tissue function in the absence of the test compound indicates that the test compound modulates the hollow tissue function, thereby identifying a compound useful for treating or preventing the hollow tissue disease.