Surgically-friendly tissue papers from organ-specific decellularized extracellular matrices

Patent metadata

Field	Value
Publication number	US-2021275724-A1
Application number	US-202117330762-A
Country	US
Kind code	A1
Filing date	May 26, 2021
Priority date	Nov 18, 2016
Publication date	Sep 9, 2021
Grant date	—

Abstract

Provided herein are inks including decellularized extracellular matrix (dECM) particles and scaffolds made from the inks. Also provided are methods of making the scaffolds and applications for the scaffolds. In an embodiment, a porous scaffold comprises dECM particles and an elastomer, wherein the scaffold is planar having a thickness of about 100 μm or greater, the scaffold comprises irregularly shaped pores having a random orientation and distribution throughout the scaffold, and the scaffold is free of crosslinking between the molecular components of the scaffold.

First claim

1 . A method of forming a porous scaffold, the method comprising:
depositing an ink onto the surface of a substrate by pouring or flowing the ink, the ink comprising an elastomer; an organic solvent system comprising an evaporant, a surfactant, and a plasticizer; and decellularized extracellular matrix (dECM) particles; and removing the organic solvent system from the ink to form a scaffold free of crosslinking between molecular components and that is not a gel.

2 . The method of claim 1 , wherein the ink is ink-free of water.

3 . The method of claim 1 , wherein the deposition step is carried out at room temperature and atmospheric pressure.

4 . The method of claim 1 , wherein the deposition step provides a layer of deposited ink having a thickness of about 100 μm or greater.

5 . A method of using the scaffold of claim 1 , the method comprising implanting the scaffold in vivo into a patient or grafting the scaffold in vivo onto a tissue or an organ of the patient.

6 . The method of claim 1 , further comprising the step of cutting or folding the scaffold in a surgical application, wherein the scaffold is mechanically robust enough to maintain its structural integrity while undergoing the cutting or folding in the surgical applications, wherein retaining its structural integrity comprises not breaking, crumbling, flaking, or tearing.

7 . The method of claim 1 , further comprising the step of suturing the scaffold to biological tissue, wherein the scaffold is mechanically robust enough to retain its structural integrity while being sutured to the biological tissue, wherein retaining its structural integrity comprises not breaking, crumbling, flaking, or tearing.

8 . The method of claim 1 , further comprising the step of applying mechanical stress to the scaffold wherein the scaffold does not undergo a solid to liquid transition upon application of the mechanical stresses.

9 . The method of claim 1 , further comprising a step of deriving the dECM particles from an ovary, muscle, liver, heart, kidney, uterus, skin, or collagen.

10 . The method of claim 1 , further comprising a step of forming an external topography that is complementary to a pattern mold.

11 . The method of claim 1 , further comprising a step of laminating a plurality of scaffolds, wherein each one of the plurality of scaffolds are derived from the same or from a different type of dECM particles than any other one of the plurality of scaffolds.

12 . The method of claim 1 , further comprising a step of fusing the scaffold and another object containing a similar elastomer as the elastomer of the scaffold.

13 . The method of claim 1 , wherein the scaffold is substantially free of liquid.

14 . The method of claim 1 , wherein the scaffold comprises irregularly shaped pores having a random orientation and distribution throughout the scaffold.

15 . The method of claim 1 , wherein the scaffold, in a dry state, exhibits a Young's modulus in the range of from about 1 MPa to about 30 MPa.

16 . The method of claim 1 , wherein the scaffold, in a dry state, exhibits an ultimate tensile strength of from about 0.1 MPa to about 1.5 MPa.

17 . The method of claim 1 , wherein the scaffold exhibits an absorbency in the range of from about 100% to about 500%.

18 . The method of claim 1 , wherein the scaffold comprises from about 30% to about 80% by weight dECM particles, based on the total solids content of the scaffold, and from about 20% to about 70% by weight elastomer, based on the total solids content of the scaffold.

19 . The method of claim 1 , wherein the scaffold comprises a synthetic powder.

20 . A method of using the scaffold of claim 1 , the method comprising use with cells, a tissue, or an organ.

21 . The method of using the scaffold of claim 20 , the method comprising supporting a population of human mesenchymal stem cells, hepatocytes or ovarian follicles at the scaffold, wherein the population retains its viability over a period of at least 28 days when the scaffold is cultured in vitro.

22 . The method of using the scaffold of claim 20 , the method comprising supporting ovarian tissue at the scaffold, wherein the ovarian tissue retains its viability over a time period of at least 8 weeks and supports development of one or more vasa-positive oocytes from the ovarian tissue when the scaffold is cultured in vitro.

23 . The method of using the scaffold of claim 20 , the method comprising supporting muscle tissue at the scaffold, wherein the muscle tissue retains its viability by integrating with the scaffold.

Assignees

• Univ Northwestern

Inventors

• Jakus Adam E
• Shah Ramille N

Classifications

• B33Y70/00

  Materials specially adapted for additive manufacturing · CPC title

• A61L27/3873

  Muscle tissue, e.g. sphincter · CPC title

• A61L2430/22

  for reconstruction of hollow organs, e.g. bladder, esophagus, urether, uterus · CPC title

• A61L27/3804

  characterised by specific cells or progenitors thereof, e.g. fibroblasts, connective tissue cells, kidney cells · CPC title

• A61L27/3895

  using specific culture conditions, e.g. stimulating differentiation of stem cells, pulsatile flow conditions · CPC title