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-9399084-B2
Publication Date
2016-07-26
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 concerns degradable bioprostheses and biologic skin substitutes that include a crosslinked collagen-based material comprising amine-based crosslinks and ester-based crosslinks. The collagen-based material has a defined level of free amines, between 50% and 85% relative to the total amount of free amines prior to crosslinking, and the crosslinked collagen-based material is characterized by a pronase digestion assay degradation rate.
The invention also tailors degradation behavior of the collagen-based material to tissue healing. In the wound-treatment context, a patient is identified as needing a degradable bioprosthesis, an approximate rate of wound healing is determined, and a degradable bioprosthesis with a degradation rate similar to the healing rate is selected and implanted over or into the wound.
In a related wound-treatment embodiment, a biologic skin substitute comprising partially crosslinked collagen is placed over a wound, where degradation progresses at or about the same rate as the wound heals. The biologic skin substitute comprises amine-based crosslinks and ester-based crosslinks, with 50% to 85% free amines relative to the total free amines prior to crosslinking.
Claims Coverage
The document includes three independent claims. Each independent claim centers on degradable, crosslinked collagen-based material comprising amine-based crosslinks and ester-based crosslinks, a defined free-amine level of 50% to 85% relative to total free amines prior to crosslinking, and degradation behavior constrained either by a pronase digestion assay degradation rate or by a match to wound-healing rate.
Positioning a degradable bioprosthesis with defined hetero-crosslinked collagen and pronase assay degradation rate
A method of treating a tissue defect comprising positioning a degradable bioprosthesis at, over, or into the tissue defect, wherein the degradable bioprosthesis comprises a crosslinked collagen-based material comprising amine-based crosslinks and ester-based crosslinks, wherein the amount of free amines on the collagen-based material is between 50% and 85% relative to the total amount of free amines prior to crosslinking, and wherein the crosslinked collagen-based material has a degradation rate between about 0.2% to about 1.0% per hour during the first 24 hours of exposure to a pronase digestion assay.
Selecting a degradable bioprosthesis with degradation rate similar to wound healing and implanting over or into the wound
A method of treating a wound comprising identifying a patient in need of a degradable bioprosthesis to aid in the healing of a wound, determining an approximate rate of healing of the wound, selecting a degradable bioprosthesis comprising a tailorably crosslinked collagen-based material having a degradation rate similar to the rate of healing of the wound, and implanting the degradable bioprosthesis over or into the wound.
Placing a partially crosslinked biologic skin substitute that degrades at or about the same rate as the wound heals
A method of treating a wound comprising providing a biologic skin substitute comprising partially crosslinked collagen and placing the skin substitute over a wound, wherein the degradation of the skin substitute progresses at or about the same rate as the wound heals, and wherein the biologic skin substitute comprises amine-based crosslinks and ester-based crosslinks with 50% to 85% free amines relative to the total amount of free amines prior to crosslinking.
Across the independent claims, the core inventive coverage is directed to degradable collagen-based bioprostheses or biologic skin substitutes comprising both amine-based crosslinks and ester-based crosslinks, with a specified free-amine level and with degradation behavior constrained either by a pronase digestion assay degradation rate window or by a requirement that degradation progress at or about the same rate as wound healing.
Stated Advantages
Degradation behavior is tailored to be similar to the rate of wound healing.
The biologic skin substitute degrades at or about the same rate as the wound heals.
Documented Applications
Treating a tissue defect by positioning a degradable bioprosthesis at, over, or into the tissue defect.
Treating a wound by selecting and implanting a degradable bioprosthesis over or into the wound.
Treating a wound by placing a biologic skin substitute over the wound such that the degradation progresses at or about the same rate as the wound heals.
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