Malleable multi-component implants and materials therefor
Described are implantable, malleable medical materials comprising mineral particles, insoluble collagen fibers, and a gel-forming polysaccharide component and/or another added gel-former. The malleable medical materials can be used treat bone or other tissue defects in patients, including in conjunction with biologically active factors such as osteogenic proteins. Also described are methods and materials that can be used to prepare the malleable medical materials.
1. An implantable medical material, comprising:
a malleable, cohesive, shape-retaining putty comprising about 40% to about 75% by weight of water;
polyethylene glycol;
said putty including mineral particles dispersed therein at a level of about 0.25 g/cc to about 0.55 g/cc, the mineral particles comprising biphasic calcium phosphate having a weight ratio of tricalcium phosphate:hydroxyapatite of about 70:30 to about 95:5;
said putty including insoluble collagen particles at a level of about 0.04 g/cc to about 0.15 g/cc, and soluble collagen particles, wherein the insoluble collagen particles to soluble collagen particles are at a weight ratio of 75:25 to about 65:35; and
said putty including a polysaccharide component at a level of about 0.01 g/cc to about 0.2 g/cc, and
said polysaccharide component comprising dextran and one or more ionic polysaccharide compounds, wherein the ionic polysaccharide compounds form anionically-cross-linked gel with one or more divalent or trivalent cations.
2. The implantable medical material of claim 1 , wherein the weight ratio of the insoluble collagen particles to the polysaccharide component in the putty is in the range of about 4:1 to about 1:1.
3. The implantable medical material of claim 1 , also comprising a biocompatible wetting agent, said wetting agent being an organic polyhydroxy compound.
4. The implantable medical material of claim 1 , also comprising a biologically active agent.
5. The implantable medical material of claim 4 , wherein said biologically active agent comprises recombinant human BMP-2.
6. The implantable medical material of claim 1 , wherein said polysaccharide component comprises alginate and starch.
7. The implantable medical material of claim 1 , wherein said polysaccharide component includes one or more members selected from the group consisting of alginate, starch, hyaluronic acid, chondroitin sulfate, dextran, dextran sulfate, heparin, heparin sulfate, heparin sulfate, chitosan, gellan gum, xanthan gum, guar gum, and K-carrageenan.
8. The implantable medical material of claim 1 further comprising a starch.
9. The implantable medical material of claim 8 further comprising an osteogenic protein.
10. The implantable medical material of claim 9 , wherein the osteogenic protein comprises a bone morphogenic protein.
11. The implantable medical material of claim 10 , wherein the one or more ionic polysaccharide compounds comprises an alginate.
12. The implantable medical material of claim 4 , wherein the biologically active agent is selected from rhBMP-7 and rhGDF-5.
13. The implantable medical material of claim 1 , wherein the cation comprises a divalent cation.
14. The implantable medical material of claim 13 , wherein the divalent cation is calcium.
15. The implantable medical material of claim 13 , wherein the divalent cation is strontium.
16. The implantable medical material of claim 1 , wherein the cation comprises aluminum.
17. The implantable medical material of claim 1 , wherein the polysaccharide compounds comprise gellan gum and carrageenans and said gellan gum and carrageenans are cross-linked.
18. The implantable medical material of claim 1 , wherein the polysaccharide component further comprises alginate.