Radiopaque injectable nucleus hydrogel compositions

摘要

A composition suitable for use as replacement material for all or part of a disc nucleus during percutaneous injection, the composition comprising:
an injectable, curable, cross-linkable, non-immunogenic non-toxic protein hydrogel that (i) the protein component of the protein hydrogel contains at least one crosslinkable amino acid (ii) has a static compressive modulus of at least about 10 kPa, and (iii) has a dynamic compressive modulus of at least about 10 kPa;an iodinated contrast solution comprising an amount of an iodine compound sufficient to increase radiopacity to a discernable level, wherein the solution causes a decrease in the static and/or dynamic compressive modulus; andan amount of a crosslinker sufficient to restore at least about 100% of the decrease in static and/or dynamic compressive modulus caused by addition of the iodinated contrast solution.

主权项

1. A composition suitable for use as a replacement material for all or part of a disc nucleus pulposus, the composition being radiopaque, injectable, non-immunogenic, non-toxic, and cross-linked, wherein the composition is made by:
(a) providing a cross-linkable protein hydrogel
comprising a protein selected from the group consisting of
NH2—(U)n6-[(Sk)2(Es)8]17-(Z)n7—COOH andNH2—(U)n6-[(Sk)2(Es)4Es′(Es)3]17-(Z)n7—COOHwherein: U and Z represent sequences useful in cloning the protein;Sk represents GlyAlaGlyAlaGlySer (SEQ ID NO: 1);Es represents GlyValGlyValPro (SEQ ID NO: 2);Es′ represents GlyLysGlyValPro (SEQ ID NO: 6) or GlyValGlyLysPro (SEQ ID NO 7);n6 and n7 independently represent 0 or 1; andwherein said protein hydrogel has a static compressive modulus of at least about 10 kPa,and a dynamic compressive modulus of at least about 10 kPa; (b) providing an iodinated contrast solution comprising an amount of an iodine compound wherein the combination of the protein hydrogel and the iodinated contrast solution has a discernable radiopacity, and has a static or dynamic compressive modulus that is decreased compared to that of the protein hydrogel alone; and (c) providing a crosslinker; (d) crosslinking the composition with using the crosslinker provided in step (c) wherein the radiopaque crosslinked composition has a static compressive modulus of at least about 10 kPa and a dynamic compressive modulus of at least about 10 kPa.