Porous carrier matrix
Medical devices, substrates and biologic therapies for bone repair and guided tissue regeneration are disclosed. More particularly, bone graft substitutes and bone void fillers which comprise a porous collagen matrix and calcium deficient hydroxyapatite ceramic granules for delivery of osteoinductive or other therapeutic agents are disclosed.
1. A composition comprising a plurality of porous CDHA granules comprising macropores and micropores, said granules having a diameter in the range of from 425 to 800 μm, a specific surface area of greater than 50 m 2 /g, a surface roughness (Ra) of at least 2.2 μm and a pH of 3.5 to 6.5; and wherein said plurality of granules has a tap density of less than 700 mg/cc; wherein said plurality of granules is admixed with a biocompatible matrix comprising an acidic collagen gel and an alkaline collagen powder, and wherein the collagen gel and collagen powder are present in the biocompatible matrix at a 1:1 ratio by dry mass.
2. The composition of claim 1 , wherein the composition comprises from 150-200 mg/cc of said granules.
3. A bone graft substitute comprising a biocompatible porous carrier matrix comprising an acidic collagen gel and an alkaline collagen powder, wherein the collagen gel and collagen powder are present in the biocompatible matrix at a 1:1 ratio by dry mass and are cross-linked, said matrix having admixed therein a plurality of porous CDHA granules having a tap density of less than 700 mg/cc, and wherein said granules have a diameter in the range of from 425 to 800 μm, a surface roughness (Ra) of at least 2.2 μm and a pH of 3.5 to 6.5; and
wherein said bone graft substitute is sterilized via exposure to E-Beam irradiation or ethyleneoxide.
4. The bone graft substitute of claim 3 further comprising an osteoinductive material, wherein said osteoinductive material is adhered to a plurality of the micropores and macropores and at least a portion of the outer surface of the granules.
5. A method of making a porous carrier matrix comprising the steps of:
a. Forming a two-phase Type I collagen mixture comprising a water-swelled acidic collagengel and an alkaline collagen powder, and adjusting the mixture to an isotonic condition and neutral pH to form a biocompatible matrix material; wherein said collagen gel and collagen powder are mixed at a 1:1 ratio by dry weight;
b. Adding a plurality of porous CDHA granules having a tap density of less than 700 mg/cc to said biocompatible matrix material to form a composite slurry, wherein said CDHA granules have a diameter of from 425-800 μm and comprise macropores and micropores, a surface roughness (Ra) of at least 2.2 μm, and a pH of 3.5 to 6.5;
c. Shaping said composite slurry into a desired size and shape to form a shaped composite slurry and lyophilizing the shaped composite slurry to form a lyophilized composite material;
d. Rehydrating the lyophilized composite material and adding a cross-linking agent to the lyophilized composite material to form a cross-linked composite material; and
e. Lyophilizing the cross-linked composite materials prior to sterilizing the cross-linked composite material via exposure to E-Beam or ethylene oxide to form a sterilized composite material.
6. The method of claim 5 , further comprising a step of exposing the sterilized composite material to a solution comprising an osteoinductive material under conditions sufficient to adhere the osteoinductive material to a plurality of the micropores and macropores and the outer surface of the granules.