Osseous regeneration in the rat calvarium using novel delivery systems for recombinant human bone morphogenetic protein-2 (rhBMP-2).
In the current investigation, we report osseous regeneration in critical-size rat calvarial defects using recombinant human bone morphogenetic protein-2 (rhBMP-2) and novel delivery systems based on biomaterials. The novel systems combine rhBMP-2 with dry powder microparticles of poly(D,L-lactide-co-glycolide) (PLGA). The mixture of rhBMP-2 with PLGA microparticles is added to an aqueous solution of biopolymer to yield a semisolid paste. The biopolymers tested include autologous blood clot, hydroxypropyl methylcellulose, and sodium alginate cross-linked with calcium ion. Insoluble collageneous bone matrix was also studied as a control. Test articles were made at 0-, 10-, and 30-micrograms doses of rhBMP-2 and imiplanted in 8-mm-diameter rat calvarial defects (which will not heal if left untreated). The animals were examined 21 days after implantation by radiography, radiomorphometry, histology, and histomorphometry. All tested materials containing rhBMP-2 restored radiopacity and normal contouring to the calvarial defects. Samples without added rhBMP-2 yielded only soft tissue within the defects. Histology showed restoration of inner and outer bone tables plus marrow constituents. The PLGA microparticles were significantly resorbed at the 21-day time point. Although small differences between delivery systems were evident at 0- and 10-micrograms rhBMP-2 doses, all test articles performed essentially equivalently at the 30-micrograms dose. Thus, novel delivery systems for rhBMP-2 offer the promise of combining the intrinsic bioactivity of the osteoinductive protein with pharmaceutically acceptable biomaterials.
Kenley
R
R
Amylin Pharmaceuticals, Inc. San Diego, California 92126.
Marden
L
L
Turek
T
T
Jin
L
L
Ron
E
E
Hollinger
J O
JO
D000464:Alginates; D000818:Animals; D001672:Biocompatible Materials; D019485:Bone Morphogenetic Proteins; D016466:CHO Cells; D006224:Cricetinae; D004337:Drug Carriers; D004343:Drug Implants; D005260:Female; D020723:Glucuronic Acid; D006133:Growth Substances / Q000008:administration & dosage*; D006603:Hexuronic Acids; D006801:Humans; D019344:Lactic Acid; D007785:Lactose / Q000031:analogs & derivatives; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives; D008863:Microspheres; D010078:Oxazines; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011506:Proteins / Q000008:administration & dosage* / Q000494:pharmacology; D011859:Radiography; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012038:Regeneration / Q000187:drug effects*; D012886:Skull / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology*
D000464:Alginates; D001672:Biocompatible Materials; D019485:Bone Morphogenetic Proteins; D004337:Drug Carriers; D004343:Drug Implants; D006133:Growth Substances; D006603:Hexuronic Acids; D010078:Oxazines; D011108:Polymers; D011506:Proteins; D011994:Recombinant Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D020723:Glucuronic Acid; D008747:Methylcellulose; C071191:MK 458; D007785:Lactose