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-12065480-B2
Publication Date
2024-08-20
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 disclosed invention provides a degradable bioprosthesis comprising a crosslinked collagen-based material. The collagen-based material includes collagen strands that comprise amine-based crosslinks, ester-based crosslinks, and free amines, and the crosslinked collagen-based material has a degradation rate between 0.27% to 0.88% per hour when subjected to a pronase digestion assay during the first 24 hours of exposure to the pronase digestion assay.
The disclosure further characterizes the crosslinked collagen-based material by defining the amine-based crosslinks with a specified structure and by including free amines within the collagen strands. In additional refinements, the degradable bioprosthesis is characterized by a shrinkage temperature (Ts) above 70°C and by a defined amount of free amines between 50% and 85%.
The disclosure also supports tailoring of crosslinking using a pH-modulated, two-buffer approach in which a collagen-based material is treated with a first buffered solution at a pH between about 8.0 to about 10.5 containing a first crosslinking agent, and further treated with a second buffered solution at a pH between about 3.0 to about 5.5 containing a second crosslinking agent. The resulting tailorably crosslinked collagen-based material is isolated as the degradable bioprosthesis.
Claims Coverage
The independent claim covers a degradable bioprosthesis formed from a crosslinked collagen-based material containing amine-based and ester-based crosslinks together with free amines, with a specific early pronase-assay degradation rate window. Additional dependent refinements further constrain structure and properties, and add a pH-modulated two-buffer crosslinking approach and collagen source.
Crosslinked collagen-based material with amine and ester crosslinks and free amines
A degradable bioprosthesis comprising a crosslinked collagen-based material, where the collagen-based material comprises collagen strands that further comprise amine-based crosslinks, ester-based crosslinks, and free amines.
Pronase-assay degradation rate in first 24 hours
The crosslinked collagen-based material has a degradation rate between 0.27% to 0.88% per hour when subjected to a pronase digestion assay during the first 24 hours of exposure to the pronase digestion assay.
Amine-based crosslink structure
The amine-based crosslinks have a structure defined in the claim.
Shrinking temperature above 70°C
The degradable bioprosthesis is characterized by having a shrinkage temperature (Ts) above 70°C.
Free amines between 50% and 85%
The degradable bioprosthesis is characterized by collagen strands having an amount of free amines between 50% and 85%.
Tailorable crosslinking via first and second buffered solutions
A method for making a degradable bioprosthesis by providing a collagen-based material, treating it with a first buffered solution containing a first crosslinking agent, further treating it with a second buffered solution containing a second crosslinking agent to tailor the crosslinking, and then isolating the resulting tailorably crosslinked collagen-based material as the degradable bioprosthesis.
Collagen strands derived from animal pericardium
The degradable bioprosthesis is characterized in that the collagen strands are derived from animal pericardium.
Overall, the claim set grounds protection in a degradable collagen bioprosthesis having both amine-based and ester-based crosslinks plus free amines, constrained by a pronase-assay degradation rate during the first 24 hours. Dependent refinements further specify amine crosslink structure, thermal stability via Ts above 70°C, free-amine content between 50% and 85%, collagen source, and a pH-modulated two-buffer approach for tailoring crosslinking.
Stated Advantages
Not explicitly described in patent.
Documented Applications
wound healing
skin substitute
tissue repair
tissue supplementation
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