Platelet-Derived Growth Factor Compositions and Methods of Use Thereof

Abstract

A method for promoting growth of bone, periodontium, ligament, or cartilage in a mammal by applying to the bone, periodontium, ligament, or cartilage a composition comprising platelet-derived growth factor at a concentration in the range of about 0.1 mg/mL to about 1.0 mg/mL in a pharmaceutically acceptable liquid carrier and a pharmaceutically-acceptable solid carrier.

What is claimed is: 
     
         1 - 78 . (canceled) 
     
     
         79 . A method for promoting growth of bone, ligament, or cartilage of a mammal comprising administering to the mammal an implant material comprising a porous calcium phosphate having a solution of platelet-derived growth factor (PDGF) disposed therein, wherein:
 a) the PDGF has a concentration in a range of about 0.1 mg/mL to about 1.0 mg/mL;   b) the calcium phosphate comprises: i) interconnected pores, ii) particles having a size ranging from about 100 microns to about 5000 microns, and iii) a porosity greater than 90%;   c) the implant material does not comprise demineralized freeze dried bone allograft; and   d) the implant material promotes the growth of the bone, ligament, or cartilage.   
     
     
         80 . The method of  claim 79 , wherein the PDGF has a concentration of about 0.3 mg/mL. 
     
     
         81 . The method of  claim 79 , wherein the PDGF has a concentration of about 1.0 mg/mL. 
     
     
         82 . The method of  claim 79 , wherein the calcium phosphate comprises tricalcium phosphate, hydroxyapatite, poorly crystalline hydroxyapatite, amorphous calcium phosphate, calcium metaphosphate, dicalcium phosphate dihydrate, heptacalcium phosphate, calcium pyrophosphate dihydrate, calcium pyrophosphate, octacalcium phosphate, or any mixture thereof. 
     
     
         83 . The method of  claim 79 , wherein the calcium phosphate comprises β-tricalcium phosphate (β-TCP). 
     
     
         84 . The method of  claim 83 , wherein the β-TCP comprises particles having a size ranging from about 100 μm to about 3000 μm. 
     
     
         85 . The method of  claim 84 , wherein the β-TCP comprises particles having a size ranging from about 250 μm to about 2000 μm. 
     
     
         86 . The method of  claim 79 , wherein the implant material delivers the PDGF to the bone, ligament, or cartilage for at least 1 day following administration. 
     
     
         87 . The method of  claim 79 , wherein the PDGF is released from the implant material upon administration at an average rate of less than or equal to 300 μg/day. 
     
     
         88 . The method of  claim 79 , wherein the solution is a pharmaceutically acceptable liquid. 
     
     
         89 . The method of  claim 79 , wherein the PDGF comprises PDGF-AA, PDGF-BB, PDGF-CC, or PDGF-DD, or a combination thereof or a derivative thereof. 
     
     
         90 . The method of  claim 79 , wherein the PDGF comprises recombinant human (rh) PDGF-BB. 
     
     
         91 . The method of  claim 90 , wherein the concentration of PDGF is about 0.3 mg/mL. 
     
     
         92 . The method of  claim 79 , wherein the concentration of PDGF is about 0.25 mg/mL to about 0.5 mg/mL. 
     
     
         93 . The method of  claim 79 , wherein the implant material consists essentially of the calcium phosphate and the PDGF, and wherein the calcium phosphate comprises tricalcium phosphate, hydroxyapatite, poorly crystalline hydroxyapatite, amorphous calcium phosphate, calcium metaphosphate, dicalcium phosphate dihydrate, heptacalcium phosphate, calcium pyrophosphate dihydrate, calcium pyrophosphate, octacalcium phosphate or any mixture thereof. 
     
     
         94 . The method of  claim 79 , wherein the implant material further comprises collagen, and the calcium phosphate comprises particles having a size ranging from about 100 μm to about 3000 μm. 
     
     
         95 . The method of  claim 93 , wherein the calcium phosphate particles have a size ranging from about 100 μm to about 3000 μm. 
     
     
         96 . The method of  claim 93 , wherein the calcium phosphate particles have a size ranging from about 250 μm to about 2000 μm. 
     
     
         97 . The method of  claim 82 , wherein the hydroxyapatite is carbonated hydroxyapatite. 
     
     
         98 . The method of  claim 79 , wherein the administering comprises applying the implant material to a bone in need of healing or regeneration. 
     
     
         99 . The method of  claim 79 , wherein the administering comprises (1) surgically exposing a bone, ligament, or cartilage treatment site; (2) removing organic matter from the treatment site; (3) implanting the implant material at the treatment site; and (4) covering the implant site with a bandage or nearby tissue. 
     
     
         100 . The method of  claim 99 , wherein the step of removing organic matter from the treatment site comprises debridement of the target tissue. 
     
     
         101 . The method of  claim 99 , wherein the implant material is prepared by: placing the calcium phosphate in a sterile dish; adding the PDGF solution sufficient to saturate the solid carrier; and mixing the solid carrier and the PDGF solution to create the implant material. 
     
     
         102 . The method of  claim 101 , further comprising allowing the implant material to sit for about 10 minutes at room temperature prior to being implanted. 
     
     
         103 . The method of  claim 99 , wherein the PDGF is applied to the treatment site in an amount equal to between about 500 ng to about 5 mg per 1 cm 2  of treatment area. 
     
     
         104 . The method of  claim 99 , wherein the PDGF is applied to the treatment site in an amount equal to between about 500 ng to about 1 mg per 1 cm 2  of treatment area. 
     
     
         105 . The method of  claim 99 , wherein the implant material is packed into a defect site at the treatment site. 
     
     
         106 . The method of  claim 99 , wherein the implant material is packed into an osseous defect site in an amount sufficient to fill the osseous defect. 
     
     
         107 . The method of  claim 99 , wherein the treatment site is irrigated with sterile saline prior to implantation of the implant material. 
     
     
         108 . The method of  claim 99 , wherein the method further comprises administering an antibiotic. 
     
     
         109 . A method for promoting growth of bone, ligament, or cartilage of a mammal comprising administering to the mammal an implant material comprising a b-tricalcium phosphate having a solution of platelet-derived growth factor (PDGF) disposed therein, wherein:
 a) the PDGF has a concentration of about 0.3 mg/mL;   b) the calcium phosphate comprises: i) interconnected pores, ii) particles having a size ranging from about 200 microns to about 3000 microns, and iii) a porosity greater than 90%;   c) the implant material does not comprise demineralized freeze dried bone allograft; and   d) the implant material promotes the growth of the bone, ligament, or cartilage.   
     
     
         110 . A method for promoting growth of bone, ligament, or cartilage of a mammal comprising administering to the mammal an implant material comprising collagen and β-tricalcium phosphate having a solution of platelet-derived growth factor (PDGF) disposed therein, wherein:
 a) the PDGF has a concentration of about 0.3 mg/mL; 
 b) the calcium phosphate comprises: i) interconnected pores, ii) particles having a size ranging from about 100 microns to about 2000 microns, and iii) a porosity greater than 90%; 
 c) the implant material does not comprise demineralized freeze dried bone allograft; and 
 d) the implant material promotes the growth of the bone, ligament, or cartilage.