Healing of large segmental defects in rat femurs is aided by RhBMP-2 in PLGA matrix.
Recombinant human bone morphogenetic protein-2 (rhBMP-2) can be used to enhance the repair of congenital or acquired bone pathologies when formulated in the appropriate carrier. Poly [D,L-(lactide-co-glycolide)] (PLGA) has been shown to be an effective carrier of rhBMP-2. We investigated several particle sizes PLGA and several doses of rhBMP-2 in a rat orthotopic model. We also investigated the effects of a fibrinolytic inhibitory agent, epsilon aminocaproic acid (EACA), on the healing response. Our data indicate that higher doses of rhBMP-2 resulted in increased failure torque (408 +/- 70 N-mm or 60% of the intact value) and higher incidence of union (100%). The induced bone in femurs treated with the smaller particle size PLGA achieved the greatest torsional stiffness and strength. The presence of rhBMP-2 was necessary for new bone to form, but the presence of EACA did not change these results; the use of the PLGA carrier appeared to increase bone strength and stiffness. In fact, with higher doses of rhBMP-2 in PLGA, the stiffness of the new bone was equal to that of intact controls (64 +/- 20 N-mm/deg [intact femurs] versus 45 +/- 10 N-mm/degree [medium dose in small PLGA], 61 +/- 17 N-mm/degree [high dose in small PLGA], and 36 +/- 11 N-mm/degree [medium dose in large PLGA]; P > .05). In conclusion, PLGA implanted with rhBMP-2 effectively aided in healing large segmental defects in rat femurs.
Lee
S C
SC
Department of Orthopaedic Surgery, Beth Israel Hospital, Boston, MA 02215.
Shea
M
M
Battle
M A
MA
Kozitza
K
K
Ron
E
E
Turek
T
T
Schaub
R G
RG
Hayes
W C
WC
D000818:Animals; D001672:Biocompatible Materials; D019485:Bone Morphogenetic Proteins; D001842:Bone and Bones / Q000187:drug effects / Q000293:injuries* / Q000502:physiology; D004337:Drug Carriers; D005269:Femur; D006133:Growth Substances / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D019344:Lactic Acid; D008863:Microspheres; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011506:Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012044:Regression Analysis; D014945:Wound Healing / Q000187:drug effects*
D001672:Biocompatible Materials; D019485:Bone Morphogenetic Proteins; D004337:Drug Carriers; D006133:Growth Substances; D011108:Polymers; D011506:Proteins; D011994:Recombinant Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid