Bone repair material and delayed drug delivery system

Claim 1

A method of making a biocompatible, osteogenic bone repair composition, said method comprising: a) dispersing a plurality of osteoinductive protein based particles in an aqueous solution of about 0.002 to about 0.25 weight percent of a crosslinking agent and surface activating or partially crosslinking said particles, said protein-based particles selected from the group consisting of demineralized bone matrix, mixtures of demineralized bone matrix and collagen, demineralized bone matrix extracted with a chaotropic agent and complexed with bone morphogenetic protein, reconstituted collagen complexed with bone morphogenctic protein, or mixtures of demineralized bone matrix extracted with a chaotropic agent and collagen complexed with bone morphogenetic protein; and b) removing the particles of step (a) from the aqueous solution; and c) milling the particles of step (b) into a powder.

Claim 2

A method of making a biocompatible, osteogenic bone repair composition, said method comprising: a) dispersing a plurality of osteoinductive protein based particles in an aqueous solution of about 0.002 to about 0.25 weight percent of a crosslinking agent and surface activating or partially crosslinking said particles, said protein-based particles selected from the group consisting of demineralized bone matrix, mixtures of demineralized bone matrix and collagen, demineralized bone matrix extracted with a chaotropic agent and complexed with bone morphogenetic protein, reconstituted collagen complexed with bone morphogenctic protein, or mixtures of demineralized bone matrix extracted with a chaotropic agent and collagen complexed with bone morphogenetic protein; and b) removing the particles of step (a) from the aqueous solution; and c) milling the particles of step (b) into a powder.

Claim 3

A method of making a biocompatible, osteogenic bone repair composition, said method comprising: a) dispersing a plurality of osteoinductive protein based particles in an aqueous solution of about 0.002 to about 0.25 weight percent of a crosslinking agent and surface activating or partially crosslinking said particles, said protein-based particles selected from the group consisting of demineralized bone matrix, mixtures of demineralized bone matrix and collagen, demineralized bone matrix extracted with a chaotropic agent and complexed with bone morphogenetic protein, reconstituted collagen complexed with bone morphogenetic protein, or mixtures of demineralized bone matrix extracted with a chaotropic agent and collagen complexed with bone morphogenetic protein; b) removing the particles of step (a) from the aqueous solution; and c) adding said particles of step (b) to an organic matrix, such that said particles become bound to the matrix.

Claim 4

A method of making a biocompatible, osteogenic bone repair composition, said method comprising: a) dispersing a plurality of osteoinductive protein based particles in an aqueous solution of about 0.002 to about 0.25 weight percent of a crosslinking agent and surface activating or partially crosslinking said particles, said protein-based particles selected from the group consisting of demineralized bone matrix, mixtures of demineralized bone matrix and collagen, demineralized bone matrix extracted with a chaotropic agent and complexed with bone morphogenetic protein, reconstituted collagen complexed with bone morphogenetic protein, or mixtures of demineralized bone matrix extracted with a chaotropic agent and collagen complexed with bone morphogenetic protein; b) removing the particles of step (a) from the aqueous solution; and c) adding said particles of step (b) to an organic matrix, such that said particles become bound to the matrix.

Claim 9

A method of making a biocompatible, osteogenic bone repair composition, comprising: a) dispersing a plurality of coated inorganic particles in an aqueous solution of about 0.002 to about 0.25 weight percent of a crosslinking agent and surface activating or partially crosslinking said coated inorganic particles; b) adding a plurality of osteoinductive particles selected from the group consisting of demineralized bone matrix, mixtures of collagen and demineralized bone matrix, demineralized bone matrix extracted with a chaotropic agent and complexed with bone morphogenetic protein; c) removing the particles of step (b) from the aqueous solution; and d) treating the particles of step (a) with carbodiimide and with an amine or diamine.

Claim 10

A method of making a biocompatible, osteogenic bone repair composition, comprising: a) dispersing a plurality of coated inorganic particles in an aqueous solution of about 0.002 to about 0.25 weight percent of a crosslinking agent and surface activating or partially crosslinking said coated inorganic particles; b) adding a plurality of osteoinductive particles selected from the group consisting of demineralized bone matrix, mixtures of collagen and demineralized bone matrix, demineralized bone matrix extracted with a chaotropic agent and complexed with bone morphogenetic protein; c) removing the particles of step (b) from the aqueous solution; and d) treating the particles of step (a) with carbodiimide and with an amine or diamine.

Claim 11

A method of making a biocompatible, osteogenic bone repair composition, said method comprising: a) subjecting a plurality of osteoinductive protein based particles to carbodiimide and an amine or a diamine, whereby a number of binding sites on said particles are increased, said protein-based particles selected from the group consisting of demineralized bone matrix, mixtures of demineralized bone matrix and collagen, demineralized bone matrix extracted with a chaotropic agent and complexed with bone morphogenetic protein, reconstituted collagen complexed with bone morphogenetic protein, or mixtures of demineralized bone matrix extracted with a chaotropic agent and collagen complexed with bone morphogenetic protein; b) dispersing said protein-based particles in an aqueous solution of about 0.002 to about 0.25 weight percent of a crosslinking agent and surface activating or partially crosslinking said particles; and c) removing said particles from the aqueous solution.

Claim 12

A method of making a biocompatible, osteogenic bone repair composition, said method comprising: a) subjecting a plurality of osteoinductive protein based particles to carbodiimide and an amine or a diamine, whereby a number of binding sites on said particles are increased, said protein-based particles selected from the group consisting of demineralized bone matrix, mixtures of demineralized bone matrix and collagen, demineralized bone matrix extracted with a chaotropic agent and complexed with bone morphogenetic protein, reconstituted collagen complexed with bone morphogenetic protein, or mixtures of demineralized bone matrix extracted with a chaotropic agent and collagen complexed with bone morphogenetic protein; b) dispersing said protein-based particles in an aqueous solution of about 0.002 to about 0.25 weight percent of a crosslinking agent and surface activating or partially crosslinking said particles; and c) removing said particles from the aqueous solution.

Claim 13

A method of making a biocompatible, osteogenic bone repair composition, said method comprising: a) dispersing a plurality of osteoinductive protein based particles in an aqueous solution of about 0.002 to about 0.25 weight percent of glutaraldehydc and surface activating or partially crosslinking said particles, said protein-based particles selected from the group consisting of demineralized bone matrix, mixtures of demineralized bone matrix and collagen, demineralized bone matrix extracted with a chaotropic agent and complexed with bone morphogenetic protein, reconstituted collagen complexed with bone morphogenetic protein, or mixtures of demineralized bone matrix extracted with a chaotropic agent and collagen complexed with bone morphogenetic protein; and b) removing the particles of step (a) from the aqueous solution; and c) adding said particles of step (b) to an organic matrix such that the particles become bound to the matrix, and wherein the step of adding an organic matrix comprises adding an organic matrix supplemented with calcium hydroxide or phospholipids.

Claim 14

A method of making a biocompatible, osteogenic bone repair composition, said method comprising: a) dispersing a plurality of osteoinductive protein based particles in an aqueous solution of about 0.002 to about 0.25 weight percent of glutaraldehydc and surface activating or partially crosslinking said particles, said protein-based particles selected from the group consisting of demineralized bone matrix, mixtures of demineralized bone matrix and collagen, demineralized bone matrix extracted with a chaotropic agent and complexed with bone morphogenetic protein, reconstituted collagen complexed with bone morphogenetic protein, or mixtures of demineralized bone matrix extracted with a chaotropic agent and collagen complexed with bone morphogenetic protein; and b) removing the particles of step (a) from the aqueous solution; and c) adding said particles of step (b) to an organic matrix such that the particles become bound to the matrix, and wherein the step of adding an organic matrix comprises adding an organic matrix supplemented with calcium hydroxide or phospholipids.

Claim 15

A method of making a biocompatible, osteogenic bone repair composition, said method comprising: a) dispersing a plurality of osteoinductive protein based particles in an aqueous solution of about 0.002 to about 0.25 weight percent of glutaraldehyde and surface activating or partially crosslinking said particles, said protein-based particles selected from the group consisting of demineralized bone matrix, mixtures of demineralized bone matrix and collagen, demineralized bone matrix extracted with a chaotropic agent and complexed with bone morphogenetic protein, reconstituted collagen complexed with bone morphogenetic protein, or mixtures of demineralized bone matrix extracted with a chaotropic agent and collagen complexed with bone morphogenetic protein; and b) removing the particles of step (a) from the aqueous solution; and c) adding said particles of step (b) to an organic matrix such that the particles become bound to the matrix and wherein the step of adding an organic matrix comprises adding an organic matrix supplemented with a bioactive protein, peptide, or drug.

Claim 16

A method of making a biocompatible, osteogenic bone repair composition, said method comprising: a) dispersing a plurality of osteoinductive protein based particles in an aqueous solution of about 0.002 to about 0.25 weight percent of glutaraldehyde and surface activating or partially crosslinking said particles, said protein-based particles selected from the group consisting of demineralized bone matrix, mixtures of demineralized bone matrix and collagen, demineralized bone matrix extracted with a chaotropic agent and complexed with bone morphogenetic protein, reconstituted collagen complexed with bone morphogenetic protein, or mixtures of demineralized bone matrix extracted with a chaotropic agent and collagen complexed with bone morphogenetic protein; and b) removing the particles of step (a) from the aqueous solution; and c) adding said particles of step (b) to an organic matrix such that the particles become bound to the matrix and wherein the step of adding an organic matrix comprises adding an organic matrix supplemented with a bioactive protein, peptide, or drug.