Continuously bioprinted multilayer tissue structure
Inventors
BEYER, Simon • Mohamed, Tamer • Pan, Sheng • WADSWORTH, Sam
Assignees
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Publication Number
US-11746333-B2
Publication Date
2023-09-05
Expiration Date
Abstract
Provided herein are synthetic living tissue structures comprising multiple layers of fibers deposited in solidified form from a 3D bioprinter, together with kits and methods of use related thereto. The fibers comprise a plurality of mammalian cells dispensed within a solidified biocompatible matrix. The structural integrity of the fiber is maintained upon and after deposition without any additional crosslinking. The fiber is continuously bioprinted through at least two layers of the structure. In one aspect, synthetic muscle tissue structures exhibit a readily assayable contractile functionality.
Core Innovation
The invention provides continuously bioprinted multilayer synthetic living tissue fibers formed by depositing mammalian cells in a solidified biocompatible matrix that maintains structural integrity and shape fidelity of the fiber upon deposition. The solidified biocompatible matrix is homogeneous in radial cross-section throughout the fiber, and the fiber maintains structural integrity and shape fidelity without additional cross-linking steps following deposition.
The continuously bioprinted fibers are formed in overlapping layers that are structurally discrete, with structural integrity of the fiber maintained between each layer. Overlapping fiber layers enable discretely separated multilayer structures, including a muscle tube or cylinder configuration and planar sheet configurations, while preserving a continuous synthetic tissue fiber architecture.
The resulting synthetic living tissue structures exhibit contractile functionality through dimensional changes measured after culturing and/or stimulation. The dimensional changes include changes in diameter, circumference, area, and/or length, and contractile behavior is characterized using test conditions and agents.
Claims Coverage
The partial content identifies one independent claim with inventive features numbering matrix homogeneity, no additional cross-linking after deposition, structurally discrete overlapping layers, contact with a test agent/condition, and determination by measuring dimensional change of the structure.
Homogeneous solidified biocompatible matrix maintaining shape fidelity without additional cross-linking
A synthetic living tissue structure comprising a continuous fiber of mammalian muscle cells dispensed from a bioprinter in overlapping layers, wherein the fiber comprises a solidified biocompatible matrix comprising the cells, the solidified biocompatible matrix is homogeneous in radial cross-section throughout the fiber, and is capable of maintaining the structural integrity and shape fidelity of the fiber upon deposition and without any additional cross-linking steps following deposition.
Structurally discrete overlapping layers with maintained structural integrity
The synthetic living tissue structure is characterized such that the structural integrity of the fiber is maintained between each layer and the layers are structurally discrete.
Evaluating contractile function by contacting with a test agent/condition
Contacting the synthetic living tissue structure with the test agent and/or condition to evaluate the effect on the contractile function of the mammalian muscle cells.
Determining effect by measuring dimensional change
Determining the effect of the agent and/or condition on the mammalian muscle cells by measuring a dimensional change in the structure.
Together, the claim coverage centers on a continuous bioprinted fiber of mammalian muscle cells in a homogeneous solidified biocompatible matrix that preserves shape fidelity without additional cross-linking, uses structurally discrete overlapping layers, and evaluates contractile function by contacting with a test agent/condition followed by measuring dimensional change.
Stated Advantages
Maintains structural integrity and shape fidelity of the fiber upon deposition without any additional cross-linking steps following deposition.
Enables determination of the effect of a test agent and/or condition on contractile function by measuring a dimensional change in the structure.
Documented Applications
Drug screening and/or agent testing by evaluating the effect of a test agent and/or condition on the contractile function of mammalian muscle cells using the synthetic living tissue structure.
Muscle repair and/or implantation using synthetic living tissue structures described as muscle tubes or related multilayer structures.
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