Method and material for enhanced tissue-biomaterial integration
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Abstract
The present invention relates to the covalent binding of a hydrogel to an extracellular matrix (ECM). The integration of the hydrogel with the tissue is superior to that in previous techniques. Moreover, unlike previous techniques, the present invention does not require a photoinitiator. Potential therapeutic applications include tissue repair and delivery of drugs or cells. The ECM is first exposed, then treated with a priming agent. Then a polymerizable agent is added and crosslinked to the ECM. Two primary embodiments of methods are disclosed. In the first, the priming agent is an oxidizer which creates tyrosyl radicals in the ECM, which are then bound by acrylate groups in the polymerizable agent. In the second, the priming agent contains aldehydes which bind amino groups in the ECM.
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Citations
75 Claims
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1-39. -39. (canceled)
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40. A method of integrating a hydrogel to a bone, comprising the steps of:
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(a) priming the bone by treating said bone with a priming agent to create a primed bone, wherein said priming agent comprises a polysaccharide with at least one aldehyde group;
(b) adding to the primed bone a polymerizable agent; and
(c) reacting the primed bone and polymerizable agent to create a hydrogel covalently bound to the bone. - View Dependent Claims (41, 42, 43, 44, 45, 46, 47, 48)
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49. A hydrogel produced by a method comprising:
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(a) priming a bone comprising a plurality of amino groups by treating the bone with a priming agent comprising a polysaccharide with at least one aldehyde group to create a primed bone, wherein said priming comprises reacting said priming agent with said bone to covalently bind said bone and said priming agent;
(b) adding to the primed bone a polymerizable agent; and
(c) reacting the primed bone and polymerizable agent to create a hydrogel covalently bound to the bone, wherein said reacting comprises covalently binding said polymerizable agent to said primed bone and crosslinking said polymerizable agent. - View Dependent Claims (50, 51, 52, 53, 54, 55, 56, 57)
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58. A method of integrating a hydrogel to an osteochondral defect, comprising the steps of:
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(a) priming the osteochondral defect by treating said osteochondral defect with a priming agent to create a primed osteochondral defect, wherein said priming agent comprises a polysaccharide with at least one aldehyde group;
(b) adding to the primed osteochondral defect a polymerizable agent; and
(c) reacting the primed osteochondral defect and polymerizable agent to create a hydrogel covalently bound to the osteochondral defect. - View Dependent Claims (59, 60, 61, 62, 63, 64, 65, 66)
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67. A hydrogel produced by a method comprising:
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(a) priming an osteochondral defect comprising a plurality of amino groups by treating the osteochondral defect with a priming agent comprising a polysaccharide with at least one aldehyde group to create a primed osteochondral defect, wherein said priming comprises reacting said priming agent with said osteochondral defect to covalently bind said osteochondral defect and said priming agent;
(b) adding to the primed osteochondral defect a polymerizable agent; and
(c) reacting the primed osteochondral defect and polymerizable agent to create a hydrogel covalently bound to the osteochondral defect, wherein said reacting comprises covalently binding said polymerizable agent to said primed osteochondral defect and crosslinking said polymerizable agent. - View Dependent Claims (68, 69, 70, 71, 72, 73, 74, 75)
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Specification