A millifluidic bioreactor system for culturing, testing, and fabricating natural or engineered cells and tissues

Available for licensing and commercial development is a millifluidic bioreactor system for culturing, testing, and fabricating natural or engineered cells and tissues.  The system consists of a millifluidic bioreactor device and methods for sample culture.  Biologic samples that can be utilized include cells, scaffolds, tissue explants, and organoids.  The system is microchip controlled and can be operated in closed-loop, providing controlled delivery of medium and biofactors in a sterile temperature regulated environment under tabletop or incubator use.  Sample perfusion can be applied periodically or continuously, in a bidirectional or unidirectional manner, and medium re-circulated.

Advantages:

• The device is small in size, and of conventional culture plate format.
• Provides the ability to grow larger biologic samples than microfluidic systems, while utilizing smaller medium volumes than conventional bioreactors.  The bioreactor culture chamber is adapted to contain sample volumes on a milliliter scale (10 [mu]L to 1 mL, with a preferred size of 100 [mu]L), significantly larger than chamber volumes in microfluidic systems (on the order of 1 [mu]L).  Typical microfluidic systems are designed to culture cells and not larger tissue samples.
• The integrated medium reservoirs and bioreactor chamber design provide for, (1) concentration of biofactors produced by the biologic sample, and (2) the use of smaller amounts of exogenous biofactor supplements in the culture medium. The local medium volume (within the vicinity of the sample) is less than twice the sample volume. The total medium volume utilized is small, preferably 2 ml, significantly smaller than conventional bioreactors (typically using 500-1000 mL).
• Provides for real-time monitoring of sample growth and function in response to stimuli via an optical port and embedded sensors.  The optical port provides for microscopy and spectroscopy measurements using transmitted, reflected, or emitted (e.g., fluorescent, chemiluminescent) light.  The embedded sensors provide for measurement of culture fluid pressure and sample pH, oxygen tension, and temperature.
• Capable of providing external stimulation to the biologic sample, including mechanical forces (e.g. fluid shear, hydrostatic pressure, matrix compression, microgravity via clinorotation), electrical fields (e.g., AC currents), and biofactors (e.g., growth factors, cytokines) while monitoring their effect in real-time via the embedded sensors, optical port, and medium sampling port.
• Monitoring of biologic sample response to external stimulation can be performed non-invasively and non-destructively through the embedded sensors, optical port, and medium sampling port.  Testing of tissue mechanical and electrical properties (e.g., stiffness, permeability, loss modulus via stress or creep test, electrical impedance) can be performed over time without removing the sample from the bioreactor device.
• The bioreactor sample chamber can be constructed with multiple levels fed via separate perfusion circuits, facilitating the growth and production of multiphasic tissues.  

Application:

Cartilage repair and methods for making tissue-engineered cartilage.

 

Development Status:

Electrospinning method is fully developed and cartilage has been synthesized. 

 

PCT Application No. PCT/US2006/028417 filed 20 Jul 2006, which published as WO 2007/012071 on 25 Jan 2007; claiming priority to 20 Jul 2005 (HHS Reference No. E-042-2005/0-PCT-02)

U.S. Patent Application filed 18 Jan 2008 (HHS Reference No. E-042-2005/0-US-03)

 

Inventors:

Juan M. Taboas (NIAMS), Rocky S. Tuan (NIAMS), et al.

 

 

Licensees Sought:

Available for exclusive or non-exclusive licensing.