Cartilage matrix
The present invention provides a cartilage matrix having a high decellularization level and a low glycosaminoglycan (GAG) content. The cartilage matrix exhibits desirable characteristics, for example, cohesiveness, tackiness and malleability, for use in cartilage repair. Also provided is a method of preparing the cartilage matrix, comprising decellularizing a cartilage to generate a decellularized cartilage, and deglycosylating the decellularized cartilage.
1. An implant comprising a composition, wherein the composition comprises a cartilage matrix putty comprising dehydrated, deglycosylated, decellularized cartilage matrix particles and water, wherein the cartilage matrix putty is prepared according to a method comprising:
(a) incubating a cartilage in a decellularization solution comprising a detergent, whereby a decellularized cartilage matrix is generated in the form of particles;
(b) deglycosylating the decellularized cartilage matrix particles, comprising treating the particles with a deglycosylation solution comprising a glycolytic enzyme, a proteolytic enzyme, an acid, hydrazine, or a combination thereof, and dehydrating the deglycosylated, decellularized cartilage matrix particles; and
(c) rehydrating the dehydrated, deglycosylated, decellularized cartilage matrix particles with a solution comprising water to yield a homogenous cartilage matrix putty;
wherein the cartilage matrix putty is cohesive, and wherein cohesive is defined as:
when a sample of the cartilage matrix putty consisting of the dehydrated, deglycosylated, decellularized cartilage matrix particles and 1 mL water per 2 grams of the dehydrated, deglycosylated, decellularized cartilage matrix particles is placed in an aqueous environment the sample of the cartilage matrix putty retains at least 95% of its weight after 180 minutes in the aqueous environment.
2. The implant of claim 1 , wherein the cartilage is selected from the group consisting of an articular cartilage, a costal cartilage, an auricular cartilage, and a nasal cartilage.
3. The implant of claim 1 , further comprising cartilage particulates.
4. A package comprising the implant of claim 1 .
5. A package comprising the implant of claim 3 .
6. A method of treating a tissue or organ defect in a subject, comprising placing the implant of claim 1 at the tissue or organ defect.
7. A method of treating a tissue or organ defect in a subject, comprising placing the implant of claim 3 at the tissue or organ defect.
8. The implant of claim 1 , wherein the particles have a diameter no greater than 150 μm.
9. The implant of claim 1 , wherein the deglycosylation solution comprises pepsin.
10. The implant of claim 1 , wherein the deglycosylation solution has a pH lower than 2.
11. The implant of claim 1 , wherein the acid is trichloroacetic acid or trifluoromethanesulfonic acid.
12. The implant of claim 1 , whereby the dehydrating comprises freeze-drying.
13. The implant of claim 1 , wherein the decellularization solution further comprises an endonuclease.
14. The implant of claim 1 , wherein the deglycosylated, decellularized cartilage matrix particles have been treated to within 10-300 μm from the surface of the deglycosylated, decellularized cartilage matrix particles.
15. The implant of claim 1 , wherein the deglycosylated, decellularized cartilage matrix particles have a specific surface area of from about 20-20,000 cm 2 /g.
16. The implant of claim 1 , wherein the deglycosylated, decellularized cartilage matrix particles comprise less than about 6 wt % of calcium based on the dry weight of the deglycosylated, decellularized cartilage matrix particles.