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Method of printing a tissue construct with embedded vasculature

a technology of tissue constructs and vasculature, which is applied in the field of tissue engineering, can solve the problems of preventing the embedding of vascular networks in tissue constructs and hindering the progress of 3d tissue engineering for decades

Pending Publication Date: 2019-01-24
PRESIDENT & FELLOWS OF HARVARD COLLEGE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

The invention described in this patent has various benefits that are not limited to one embodiment. These benefits include improved efficiency, reduced labor costs, and increased productivity. However, not all advantages will be present in every embodiment.

Problems solved by technology

The inability to embed vascular networks in tissue constructs has hindered progress on 3D tissue engineering for decades.

Method used

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  • Method of printing a tissue construct with embedded vasculature
  • Method of printing a tissue construct with embedded vasculature
  • Method of printing a tissue construct with embedded vasculature

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Fugitive Ink

[0123]Referring to FIG. 6A, highly concentrated (40 wt. %) Pluronic F127A, which exhibits a strong shear-thinning response when the applied shear stress exceeds the shear yield stress (τy) (e.g., during printing), as well as a plateau shear elastic modulus (G′) that exceeds the shear viscous modulus (G″) when the applied shear stress is below τy (e.g., after printing), is selected as the fugitive ink for an exemplary system. The fugitive ink elasticity is found to be about 2×104 Pa at 22° C., as shown in FIG. 6B. Below the CMT (about 4° C.), the ink liquefies and its elasticity decreases by several orders of magnitude, thereby facilitating its removal from the tissue construct.

[0124]As described above, the sacrificial filaments formed from the fugitive ink may include one or more additional cells, growth factors, drugs, etc. For example, endothelial, epithelial and / or other cells may be dispersed within the fugitive ink and deposited with the sacrificial filaments. When ...

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Abstract

A printed tissue construct comprises one or more tissue patterns, where each tissue pattern comprises a plurality of viable cells of one or more predetermined cell types. A network of vascular channels interpenetrates the one or more tissue patterns. An extracellular matrix composition at least partially surrounds the one or more tissue patterns and the network of vascular channels. A method of printing a tissue construct with embedded vasculature comprises depositing one or more cell-laden filaments, each comprising a plurality of viable cells, on a substrate to form one or more tissue patterns. Each of the one or more tissue patterns comprises one or more predetermined cell types. One or more sacrificial filaments, each comprising a fugitive ink, are deposited on the substrate to form a vascular pattern interpenetrating the one or more tissue patterns. The vascular pattern and the one or more tissue patterns are at least partially surrounded with an extracellular matrix composition. The fugitive ink is then removed to create vascular channels in the extracellular matrix composition, thereby forming an interpenetrating vascular network in a tissue construct.

Description

RELATED APPLICATIONS[0001]The present patent document claims the benefit of priority under 35 U.S.C. § 119 to U.S. Provisional Patent Application Ser. No. 61 / 900,029, which was filed on Nov. 5, 2013, and which is hereby incorporated by reference in its entirety.[0002]The following patents and patent application publications are also hereby incorporated by reference in their entirety: International Patent Application Serial No. PCT / US2012 / 044794, entitled “Multinozzle Deposition System for Direct Write Applications,” filed Jun. 29, 2012; U.S. Patent Application Publication No. 2013 / 0084449, entitled “Viscoelastic Ink for Direct Writing of Hydrogel Structures,” which was filed as PCT / US2011 / 29429 on Mar. 22, 2011; and U.S. Pat. No. 8,101,139, entitled “Microcapillary Networks,” filed on Jun. 5, 2008.FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0003]This invention was made with government support under contract number DMR 0820484 awarded by the National Science Foundation. The governmen...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61L27/50A61L27/22B33Y80/00B29C64/40A61L27/38A61L27/36B33Y10/00A61F2/10A61F2/06B29C64/106C12M1/26
CPCC12M33/00A61F2240/002B29C64/106A61L2430/34A61F2/105A61L27/507A61L27/3813A61L27/3633A61L27/225A61L27/222B33Y10/00B33Y80/00A61F2/06A61L27/3808A61L27/3826B29C64/40B33Y70/00B29C64/118
Inventor LEWIS, JENNIFER A.KOLESKY, DAVID B.SKYLAR-SCOTT, MARK A.HOMAN, KIMBERLY A.TRUBY, RYAN L.GLADMAN, AMELIA SYDNEY
Owner PRESIDENT & FELLOWS OF HARVARD COLLEGE
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