Crosslinked human or animal tissue products and their methods of manufacture and use
Inventors
Mezger, W. Jerry • Myers, Keith E.
Assignees
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Publication Number
US-8901078-B2
Publication Date
2014-12-02
Expiration Date
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 invention relates to degradable collagen-based bioprostheses and to cross-linked collagen-based materials that include Crosslink A, Crosslink B, and free amines (—NH2). The crosslinks are defined by specific substituent structures (R1, R2, R3, and R4), with R1 and R2 selected from —CH2—O—(CH2)n—O—CH2— and —CH2—(O(CH2)n)m—O—CH2—, where n and m are independently an integer from 1 to 6.
The material requires that 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. The ratio of Crosslink A and Crosslink B is from about 80:20 to about 20:80, and the degradation rate is bounded using a pronase digestion assay.
The invention addresses the production of degradable collagen-based bioprostheses with degradation that can be adjusted to clinically relevant timeframes for biomedical use, including wound healing, skin substitute, and tissue repair. Partially crosslinked collagen products and associated medical treatment methods are also described.
Claims Coverage
The independent claims define a degradable collagen-based bioprosthesis or cross-linked collagen-based material with Crosslink A, Crosslink B, and free amines (—NH2), together with structural substituent definitions, quantitative constraints on free-amine content and crosslink ratio, and a pronase digestion assay degradation-rate limitation.
Cross-linked collagen-based material with Crosslink A, Crosslink B, and free amines
A cross-linked collagen-based material comprising Crosslink A, Crosslink B, and free amines (—NH2), wherein R1 is R2 is R3 and R4 are independently selected from —CH2—O—(CH2)n—O—CH2— and —CH2—(O(CH2)n)m—O—CH2—, n and m are independently an integer from 1 to 6, 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 Crosslink A and Crosslink B is from about 80:20 to about 20:80.
Degradable bioprosthesis comprising a cross-linked collagen-based material with Crosslink A, Crosslink B, and free amines
A degradable bioprosthesis comprising a cross-linked collagen-based material comprising Crosslink A, Crosslink B, and free amines (—NH2), wherein R1 is R2 is R3 and R4 are independently selected from —CH2—O—(CH2)n—O—CH2— and —CH2—(O(CH2)n)m—O—CH2—, n and m are independently an integer from 1 to 6, 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 Crosslink A and Crosslink B is from about 80:20 to about 20:80.
Degradable bioprosthesis with tailorable cross-linked collagen-based material and pronase digestion degradation rate
A degradable bioprosthesis comprising a tailorable cross-linked collagen-based material comprising Crosslink A, Crosslink B, and free amines (—NH2), wherein R1 is R2 is R3 and R4 are independently selected from —CH2—O—(CH2)n—O—CH2— and —CH2—(O(CH2)n)m—O—CH2—, n and m are independently an integer from 1 to 6, and the tailorable cross-linked collagen-based material has a degradation rate between 0.27% to 0.88% per hour when subjected to a pronase digestion assay.
Across the independent claims, the coverage centers on a collagen-based crosslinked bioprosthesis that includes amine-based Crosslink A and ester-based Crosslink B together with free amines (—NH2), with quantitative constraints on free-amine content and Crosslink A:Crosslink B ratios. Additional independent-claim coverage specifies a bounded degradation rate under a pronase digestion assay.
Stated Advantages
Enables degradation tuning of degradable collagen-based bioprostheses by controlling crosslink composition to achieve adjustable degradation and protease resistance.
Supports achieving clinically relevant degradation timeframes for wound healing, skin substitute, and tissue repair.
Documented Applications
Wound healing.
Skin substitute.
Tissue repair.
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