title: Preliminary in vivo studies on the osteogenic potential of bone morphogenetic proteins delivered from an absorbable puttylike polymer matrix.
abstract: This article describes preliminary in vivo studies evaluating the osteogeneic potential of bone morphogenetic proteins (BMPs) delivered from an absorbable puttylike polymer matrix. In the first study, bovine-derived bone morphogenetic proteins were incorporated in an polymer matrix consisting of 50:50 poly(DL-lactide-co-glycolide) dissolved in N-methyl-2-pyrrolidone. The matrix was implanted in an 8 mm critical-size calvarial defect created in the skull of adult Sprague-Dawley rats (n = 5 per treatment group). After 28 days, the implant sites were removed and examined for new bone formation, polymer degradation, and tissue reaction. Gamma-irradiated polymer matrices appeared to give more bone formation than nonirradiated samples (histological analysis; 2. 76 + 1.34 mm(2) of bone versus 1.30 + 0.90 mm(2) of bone, respectively and x-ray analysis; 27.2 + 15.9 mm(2) of bone versus 20. 7 + 16.7 mm(2) of bone, respectively) and less residual polymer (0.0 + 0.0 versus 0.2 + 0.4, respectively). The polymer implants with bone morphogenetic protein also gave less inflammatory response than the polymer controls (gamma irradiated polymer/BMP = 1.8 + 0.4 and nonirradiated polymer/BMP = 1.2 + 0.4 versus polymer only = 3.0 + 1. 2, respectively). However, despite trends in both the x-ray and histological data there was no statistical difference in the amount of new bone formed among the four treatment groups (P > 0.05). This was most likely due to the large variance in the data scatter and the small number of animals per group. In the second animal study, bovine-derived BMPs and the polymeric carrier were gamma irradiated separately, at doses of 1.5 or 2.5 Mrad, and their ability to form bone in a rat skull onlay model was evaluated using Sprague-Dawley rats (n = 5 per treatment group). Histomorphometry of skull caps harvested 28 days after implantation showed no significant differences as compared to non-irradiated samples, in implant area, new bone area, and percent new bone (P > 0.05). These results suggest gamma irradiation may be useful in sterilization of the bovine-derived BMPs and the polymeric carrier for potential bone repair and/or regeneration applications.
authors.affiliation: Atrix Laboratories, Inc., 2579 Midpoint Drive, Fort Collins, Colorado 80525, USA. kandriano@aol.com
authors.forename: K P
authors.initials: KP
authors.lastname: Andriano
authors.forename: B
authors.initials: B
authors.lastname: Chandrashekar
authors.forename: K
authors.initials: K
authors.lastname: McEnery
authors.forename: R L
authors.initials: RL
authors.lastname: Dunn
authors.forename: K
authors.initials: K
authors.lastname: Moyer
authors.forename: C M
authors.initials: CM
authors.lastname: Balliu
authors.forename: K M
authors.initials: KM
authors.lastname: Holland
authors.forename: S
authors.initials: S
authors.lastname: Garrett
authors.forename: W E
authors.initials: WE
authors.lastname: Huffer
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D016723:Bone Remodeling / Q000187:drug effects / Q000528:radiation effects; D002417:Cattle; D003692:Delayed-Action Preparations; D017102:Fracture Healing / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays; D008297:Male; D008422:Materials Testing; D010012:Osteogenesis / Q000187:drug effects* / Q000528:radiation effects; D011108:Polymers; D051381:Rats; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000187:drug effects / Q000293:injuries / Q000528:radiation effects
chemical_list: D001672:Biocompatible Materials; D019485:Bone Morphogenetic Proteins; D003692:Delayed-Action Preparations; D011108:Polymers