Preliminary in vivo studies on the osteogenic potential of bone morphogenetic proteins delivered from an absorbable puttylike polymer matrix

• Published in: Journal of biomedical materials research 2000, Vol.53 (1), p.36-43
• Main Authors: Andriano, Kirk P., Chandrashekar, Bhagya, McEnery, Kathleen, Dunn, Richard L., Moyer, Katie, Balliu, Catherine M., Holland, Kathleen M., Garrett, Steven, Huffer, William E.
• Format: Article
• Language: English
• Subjects: Animals; Biocompatible Materials; biodegradable polymers; Biological and medical sciences; Bone; bone morphogenetic protein; Bone Morphogenetic Proteins - administration & dosage; bone regeneration; Bone Remodeling - drug effects; Bone Remodeling - radiation effects; Carboxylic acids; Cattle; Controlled drug delivery; Copolymers; Delayed-Action Preparations; Fracture Healing - drug effects; Fracture Healing - radiation effects; gamma radiation sterilization; Gamma Rays; Irradiation; Living systems studies; Male; Materials Testing; Medical sciences; Orthopedic surgery; Osteogenesis - drug effects; Osteogenesis - radiation effects; Physiological models; Polymers; Proteins; Rats; Rats, Sprague-Dawley; Skull - drug effects; Skull - injuries; Skull - radiation effects; Sterilization (cleaning); Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
• ISSN: 0021-9304; 1097-4636
• DOI: 10.1002/(SICI)1097-4636(2000)53:1<36::AID-JBM5>3.0.CO;2-H

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 mm2 of bone versus 1.30 + 0.90 mm2 of bone, respectively and x‐ray analysis; 27.2 + 15.9 mm2 of bone versus 20.7 + 16.7 mm2 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. © 2000 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 53: 36–43, 2000