Tissue substitute multilayer matrix and uses thereof
Compositions-of-matter comprising a matrix made of one or more, preferably two or more elastic layers and one or more viscoelastic layer are disclosed. The compositions-of-matter are characterized by high water-impermeability and optionally by self-recovery. Processes of preparing the compositions-of-matter and uses thereof as tissue substitutes or for repairing damaged tissues are also disclosed.
1. A composition-of-matter comprising a multi-layer matrix, said matrix comprising at least one layer of an elastic polymeric material and at least one layer of a viscoelastic polymeric material, wherein at least one layer of said elastic polymeric material is in a form of a porous layer of polymeric fibers, and wherein said viscoelastic polymeric material comprises a polymer characterized by a glass transition temperature and/or melting point at a temperature below 40° C., said elastic polymeric material comprises a polymer characterized by a glass transition temperature and/or melting point at a temperature above 40° C., and wherein said layer of said viscoelastic polymeric material is characterized by a loss tangent (G″/G′) at a temperature of 10° C. and frequency of 0.1 Hz which is in a range of from 0.01 to 4.
2. The composition-of-matter of claim 1 , comprising at least two layers of said elastic polymeric material, each of said layers is independently in a form of a porous layer of polymeric fibers, wherein said layer of a viscoelastic polymeric material is interposed between two of said layers of an elastic polymeric material.
3. The composition-of-matter of claim 1 , wherein each layer of said elastic polymeric material is a porous layer characterized by a porosity of at least 50%.
4. The composition-of-matter of claim 1 , wherein said polymeric fibers are characterized by a mean diameter in a range of from 0.001 to 30 μm.
5. The composition-of-matter of claim 1 , wherein said layer of a viscoelastic polymeric material is characterized by at least one of:
a) a storage shear modulus (G′) in a range of from 0.01 to 10 MPa, at a temperature of 10° C. and frequency of 0.1 Hz; and
b) a loss shear modulus (G″) in a range of from 0.0001 to 2 MPa, at a temperature of 10° C. and frequency of 0.1 Hz.
6. The composition-of-matter of claim 1 , wherein polymeric fibers comprise electrospun elastic polymeric material.
7. The composition-of-matter of claim 1 , wherein said layer of a viscoelastic polymeric material is characterized by a porosity in a range of from 0 to 50%.
8. The composition-of-matter of claim 1 , wherein said elastic polymeric material is biocompatible.
9. The composition-of-matter of claim 1 , wherein said matrix is characterized by a thickness of less than 3 mm.
10. The composition-of-matter of claim 1 , wherein each of said layers of an elastic polymeric material is characterized by an elastic modulus in a range of from 1 kPa to 10 MPa, as determined in accordance with ASTM international standard D882-12.
11. The composition-of-matter of claim 1 , wherein each of said layers of an elastic polymeric material is characterized by an elongation at failure of at least 100%.
12. The composition-of-matter of claim 1 , wherein each of said layers of an elastic polymeric material is characterized by an ultimate tensile strength of at least 0.05 MPa.
13. The composition-of-matter of claim 1 , wherein said matrix is characterized by an elastic modulus which is within a range of 80% to 120% of an elastic modulus of at least one of said elastic layers.
14. The composition-of-matter of claim 1 , wherein at least one of said layers of an elastic polymeric material comprises an electrospun polymeric material.
15. The composition-of-matter of claim 1 , wherein said viscoelastic polymeric material comprises poly(lactic acid-co-ε-caprolactone).
16. The composition-of-matter of claim 1 , wherein said matrix is characterized by a water-permeability of less than 1 ml per hour per cm 2 upon exposure to an aqueous liquid at a pressure of 40 mmHg.
17. The composition-of-matter of claim 1 , further comprising at least one additional ingredient, said additional ingredient being in a form of an additional layer on at least a portion of at least one surface of said matrix and/or dispersed within and/or on at least one surface of said matrix, said at least one additional ingredient imparting an additional functionality.
18. The composition-of-matter of claim 1 , being a suturable and/or stapleable matrix capable of self-recovery.
19. An article-of-manufacture comprising the composition-of-matter or matrix of claim 1 , the article-of-manufacture being a medical device.
20. A method of repairing and/or substituting a biological tissue in a subject in need thereof, the method comprising contacting the biological tissue with the article-of-manufacture of claim 19 , thereby repairing and/or substituting the biological tissue.
21. The method of claim 20 , wherein said repairing and/or substituting a biological tissue comprises suturing and/or stapling the article-of-manufacture to the tissue.
22. A process for preparing the composition-of-matter of claim 1 , the process comprising forming said layers of an elastic polymeric material and said at least one layer of a polymeric viscoelastic layer by continuous electrospinning.
23. A process for preparing the composition-of-matter of claim 1 , the process comprising forming said layers of an elastic polymeric material by electrospinning, placing said at least one layer of a viscoelastic polymeric material parallel to said layers of an elastic polymeric material, and pressing said layers of an elastic polymeric material and said at least one layer of a viscoelastic polymeric material together, thereby forming said composition-of-matter.
24. A composition-of-matter comprising a multi-layer, suturable and/or stapleable matrix, said matrix comprising (i) at least one layer of an elastic polymeric material characterized by a recovery of at least 75%, and (ii) at least one layer of a viscoelastic polymeric material characterized by a loss tangent (G″/G′) at a temperature of 10° C. and frequency of 0.1 Hz which is in a range of from 0.02 to 1.
25. The composition-of-matter of claim 24 , wherein said at least one layer of an elastic polymeric material is a porous layer characterized by a porosity of at least 50%.
26. The composition-of-matter of claim 24 , wherein said at least one layer of an elastic polymeric material comprises polymeric fibers.
27. The composition-of-matter of claim 24 , wherein at least one layer of said viscoelastic polymeric material is interposed between two layers of said elastic polymeric material.
28. The composition-of-matter of claim 24 , wherein said layer of a viscoelastic polymeric material is characterized by at least one of:
a) a storage shear modulus (G′) in a range of from 0.01 to 10 MPa, at a temperature of 10° C. and frequency of 0.1 Hz;
b) a loss shear modulus (G″) in a range of from 0.0001 to 2 MPa, at a temperature of 10° C. and frequency of 0.1 Hz; and
c) a glass transition temperature and/or melting point of said viscoelastic polymeric material which is at a temperature below 40° C.
29. The composition-of-matter of claim 24 , wherein each of said layers of an elastic polymeric material is characterized by an elastic modulus in a range of from 1 kPa to 10 MPa, as determined in accordance with ASTM international standard D882-12.
30. The composition-of-matter of claim 24 , wherein said matrix is characterized by a water-permeability of less than 1 ml per hour per cm 2 upon exposure to an aqueous liquid at a pressure of 40 mmHg.
31. An article-of-manufacture comprising the composition-of-matter or matrix of claim 24 , the article-of-manufacture being a medical device.
32. A method of repairing and/or substituting a biological tissue in a subject in need thereof, the method comprising contacting the biological tissue with the article-of-manufacture of claim 31 , thereby repairing and/or substituting the biological tissue.
33. A composition-of-matter comprising a multi-layer, suturable and/or stapleable matrix, said matrix comprising at least one layer of an elastic polymeric material characterized by a recovery of at least 75%, and at least one layer of a viscoelastic polymeric material,
wherein said layer of a viscoelastic polymeric material is characterized by at least one of:
a) a storage shear modulus (G′) in a range of from 0.01 to 10 MPa, at a temperature of 10° C. and frequency of 0.1 Hz;
b) a loss shear modulus (G″) in a range of from 0.0001 to 2 MPa, at a temperature of 10° C. and frequency of 0.1 Hz;
c) a glass transition temperature and/or melting point of said viscoelastic polymeric material which is at a temperature below 40° C.; and
d) a loss tangent (G″/G′) at a temperature of 10° C. and frequency of 0.1 Hz which is in a range of from 0.02 to 1,
and wherein said layer of an elastic polymeric material is characterized by at least one of:
a) an elastic modulus in a range of from 1 kPa to 10 MPa, as determined in accordance with ASTM international standard D882-12;
b) an elongation at failure in a range of at least 100%; and
c) a glass transition temperature and/or melting point of said elastic polymeric material which is at a temperature above 40° C.