Decellularization method and system and decellularized tissue formed thereby
Systems and methods that establish a pressure differential across a tissue wall to encourage complete decellularization of the wall are described. The methods can be utilized for decellularization of blood vessel tissue including heart valves and surrounding tissues. The methods and systems can essentially completely decellularize the treated tissue segments. Systems can be utilized to decellularize one or multiple tissue segments at a single time.
1. A system for decellularizing a tissue segment comprising:
a decellularization chamber;
a first tissue holder that is removably attachable to a first end of a tissue segment, the tissue segment comprising a lumen and a tissue wall surrounding the lumen, the tissue wall having an interior surface facing the lumen and an exterior surface opposite the interior surface;
a second tissue holder that is removably attachable to a second end of the tissue segment, wherein upon attachment of a tissue segment to the first and second tissue holders and placement of the tissue segment in the decellularization chamber, a flow path is established that passes through the lumen of the tissue segment and contacts the interior surface of the tissue segment;
a first flow line;
a second flow line in fluid communication with and downstream of the first flow line, wherein upon assembly of the system with a tissue segment, the flow path sequentially exits the lumen of the tissue segment, passes through the first flow line, passes through the second flow line, enters the decellularization chamber and contacts the exterior surface of the tissue wall;
a pump configured for pumping a decellularization solution through the flow path; and
a control system configured to control characteristics of the decellularization solution along the flow path and thereby establish a pressure differential across the tissue wall.
2. The system of claim 1 , the control system comprising a valve between the first flow line and the second flow line.
3. The system of claim 1 , further comprising a reservoir for containing an amount of the decellularization solution.
4. The system of claim 1 , further comprising a plate that separates the decellularization chamber into a first section and a second section, the first tissue holder being removably attachable to the plate.
5. The system of claim 1 , wherein the system is configured to contain multiple tissue segments.
6. The system of claim 1 , further comprising a heater configured to heat the decellularization solution.
7. The system of claim 1 , wherein the control system is configured to establish the pressure differential with a higher pressure at the interior surface of the tissue segment as compared to the pressure at the exterior surface of the tissue segment.
8. The system of claim 1 , wherein the control system is configured to pulse the pressure differential.
9. The system of claim 1 , wherein the control system is configured to cyclically stop and start the flow along the flow path.
10. The system of claim 1 , wherein the pump is a peristaltic pump.