Crosslinked human or animal tissue products and their methods of manufacture and use

Inventors

Mezger, W. Jerry • Myers, Keith E.

Assignees

HARBOR MEDTECH Inc

Abstract

Degradable bioprostheses made of collagen-based material having amine-based and ester-based crosslinks are provided, as are methods for their formation and use. Some embodiments of the present invention are directed towards a method of controlling the ratio of amine-based crosslinks to ester-based crosslinks within a collagen-based material to provide a tailorably crosslinked collagen-based material. Some embodiments provide a method of making a degradable bioprosthesis involving controlling crosslinking to afford a degradable bioprosthesis that is partially crosslinked. By controlling the ratio of amine-based to ester-based crosslinks, by controlling the level of crosslinking, or by controlling both of these features, degradable bioprostheses with tailored degradation rates can be synthesized. Some embodiments of degradable bioprostheses have degradation rates that are tailored to allow their use in particular medical applications. Some embodiments are directed towards methods of use degradable bioprostheses in wound healing, tissue repair, and tissue supplementation.

Core Innovation

The disclosed invention relates to crosslinked collagen-based materials that include both amine-based crosslinks and ester-based crosslinks. The crosslinked collagen-based material includes Crosslink A and Crosslink B, wherein R1, R2, R3 and R4 are each –CH2–O–(CH2)n–O–CH2 and n is 4, and wherein the material includes collagen.

The invention further defines the amount of free amines (–NH2) and the relationship between amine-based crosslinks and ester-based crosslinks. The amount of free amines (–NH2) on the collagen strands is between 50% and 85% relative to the total amount of free amines (–NH2) prior to crosslinking, and the ratio of amine-based crosslinks to ester-based crosslinks is about 100:1 to about 1:100.

The invention is also described as addressing degradable bioprostheses that include the crosslinked collagen-based material. A degradable bioprosthesis comprises a crosslinked collagen-based material comprising Crosslink A, Crosslink B, and free amines (–NH2), with the same structural definitions for R1–R4 and n = 4, and a degradation rate between about 0.2% and about 1.0% per hour during the first 24 hours of exposure to a pronase digestion assay.

Claims Coverage

The independent claims identified are clm-00001, clm-00006, and clm-00011, each centered on crosslinked collagen-based materials with amine-based and ester-based crosslinks and performance defined by pronase digestion degradation rate. Across the independent claims, three main inventive-feature themes appear: the crosslinked collagen composition with Crosslink A and Crosslink B defined by R1–R4 (n = 4), the pronase assay degradation-rate window of 0.2% to 1.0% per hour during the first 24 hours, and compositional constraints involving free amines (–NH2) and the amine-to-ester crosslink ratio.

Overall, the independent claims cover crosslinked collagen-based materials defined by Crosslink A and Crosslink B structures (R1–R4 with n = 4) and a pronase digestion degradation-rate window of about 0.2% to about 1.0% per hour during the first 24 hours. Coverage also extends to degradable bioprostheses comprising the crosslinked collagen-based material, and includes compositional control using free amines (–NH2) content (50% to 85% relative to total free amines prior to crosslinking) and an amine-based to ester-based crosslink ratio (about 100:1 to about 1:100).

Stated Advantages

Documented Applications