Biomatrix hydrogels and methods of use thereof
This invention is directed to aragonite and calcite hydrogel biomatrices, optionally seeded with precursor cells and uses thereof in tissue engineering, regeneration and repair, including in inducing or enhancing bone formation, cartilage formation or a combination thereof in a subject, and kits related thereto.
1. A hydrogel biomatrix cement comprising
(a) a hydrogel that comprises a biocompatible polymer and a coral or coral derivative biomatrix,
the biomatrix being in the form of a powder, granule, bead, emulsion, suspension, paste or putty,
wherein the coral or coral derivative biomatrix in the powder, granule, bead, emulsion, suspension, paste or putty was prepared from coral characterized as having a specific fluid uptake capacity value of at least 75%,
which specific fluid uptake capacity value is a percentage determined by establishing a spontaneous fluid uptake value divided by a total fluid uptake value using water, and
wherein the biocompatible polymer is not a natural polymer,
the hydrogel being mixed with
(b) β-tricalcium phosphate, monocalcium phosphate monohydrate, dicalcium phosphate, tetra-calcium phosphate, calcium sulfate or hydroxyapatite,
wherein the spontaneous fluid uptake is the difference in weight of the biomatrix before and after contacting dried biomatrix with the fluid for 0.1-1 minute, and the total fluid uptake is the difference in weight of the biomatrix before and after contacting biomatrix with fluid under vacuum for a period of time sufficient to ensure maximal uptake of the fluid into the matrix.
2. The hydrogel biomatrix cement of claim 1 , wherein said coral or coral derivative from which the biomatrix in the powder, granule, bead, emulsion, suspension, paste or putty was prepared is characterized by also having a contact angle value of less than 70 degrees, when in contact with a fluid.
3. The hydrogel biomatrix cement of claim 1 , wherein said derivative is a coral.
4. The hydrogel biomatrix cement of claim 3 , wherein said coral or coral derivative is aragonite, calcite, hydroxyapatite, mixtures thereof, or other polymorphs of the same.
5. The hydrogel biomatrix cement of claim 1 , wherein said powder, granules, beads, emulsion, suspension, paste or putty comprises aragonite or calcite particles.
6. The hydrogel biomatrix cement of claim 5 , wherein said aragonite or calcite particles are about 1-20 microns in diameter.
7. The hydrogel biomatrix cement of claim 5 , wherein said aragonite or calcite particles are about 20-400 microns in diameter.
8. The hydrogel biomatrix cement of claim 5 , wherein said aragonite or calcite particles are about 50-800 nanometers in diameter.
9. The hydrogel biomatrix cement of claim 1 , wherein said biomatrix comprises aragonite or calcite conjugated to said hydrogel.
10. The hydrogel biomatrix cement of claim 9 , wherein said hydrogel comprises platelet rich plasma, a glycosaminoglycan or a combination thereof.
11. The hydrogel biomatrix cement of claim 1 , wherein said cement further comprises a cytokine, a growth factor, a chelator, a cell population, a therapeutic compound, a drug, or any combination thereof.
12. The hydrogel biomatrix cement of claim 11 , wherein said biomatrix comprises said therapeutic compound or drug, and said therapeutic compound or drug comprises an anti-inflammatory compound, an anti-infective compound, a pro-angiogenic factor or a combination thereof.
13. The hydrogel biomatrix cement of claim 1 , wherein said hydrogel further comprises a chondrogenic support agent, an osteogenic support agent or a combination thereof.
14. The hydrogel biomatrix cement of claim 1 , wherein the hydrogel is in gel form.
15. The hydrogel biomatrix cement of claim 1 , wherein the biomatrix is in the form of an emulsion, suspension, paste or putty.
16. A kit for tissue engineering, tissue regeneration or tissue repair comprising the hydrogel biomatrix cement of claim 1 .
17. A method of tissue engineering, tissue regeneration or tissue repair in a subject comprising administering to said subject the hydrogel biomatrix cement of claim 1 .
18. The method of claim 17 , wherein said biomatrix cement is seeded with a precursor cell that can participate in said tissue engineering, tissue regeneration or tissue repair.
19. The method of claim 17 , wherein said tissue engineering, tissue regeneration or tissue repair results in the induction or enhancement of bone formation, cartilage formation or a combination thereof.
20. The method of claim 19 , wherein said subject has osteoporosis.
21. The method of claim 19 , wherein said subject has Paget's disease, fibrous dysplasia or osteodystrophy.
22. The method of claim 19 , wherein said subject has bone infirmity.
23. The method of claim 19 , wherein said hydrogel is administered to a site of bone infirmity.
24. The method of claim 19 , wherein said enhancing bone formation comprises healing non-union fractures.
25. The method of claim 19 , wherein said method treats a cartilage defect or disorder in said subject.
26. The method of claim 25 , wherein said cartilage defect or disorder comprises a full thickness articular cartilage defect; osteoarthritis, a joint defect or a defect resulting from trauma, sports, or repetitive stress.
27. The method of claim 19 , wherein said tissue engineering, tissue regeneration or tissue repair results in the induction or enhancement of cartilage formation.
28. The method of claim 27 , wherein said method further comprises exposing said site of cartilage repair, and optionally exposing bone tissue located proximally to the site of cartilage repair in said subject and implanting said hydrogel biomatrix cement therein.
29. The method of claim 28 , further comprising the step of affixing at least a portion of said hydrogel biomatrix cement to bone located proximally to said site of cartilage repair.
30. The method of claim 28 , wherein said method promotes adhesion, proliferation or differentiation, or a combination thereof, of a cell population at said site of cartilage repair.
31. The method of claim 28 , further comprising seeding said biomatrix with mesenchymal stem cells prior to said implanting.
32. The method of claim 28 , wherein said method comprises positioning said hydrogel biomatrix cement below the upper limit of said site such that said hydrogel biomatrix cement does not protrude above an upper limit of said site.
33. The method of claim 19 , wherein said subject is afflicted with a cartilage and/or bone defect or disorder or disease.
34. The method of claim 19 , wherein said cartilage defect or disorder comprises a full or partial thickness articular cartilage defect; osteochondral defect; osteoarthritis, bone marrow edema, a joint defect or a defect resulting from trauma, sports, repetitive stress or osteoarthritis.
35. The method of claim 17 , wherein said hydrogel biomatrix cement can be used as a bone filler or bone substitute material.
36. The method of claim 17 , wherein said hydrogel biomatrix cement further comprises a bone filler or bone substitute material.
37. The method of claim 17 , wherein said coral derivative comprises hydroxyapatite.
38. The method of claim 17 , wherein said method further comprises forming a three-dimensional bone filler in sequential cross-sectional layers in accordance with a model of the bone filler, comprising said hydrogel biomatrix cement.