Preliminaryin 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.

Gamma Irradiation and Ethylene Oxide in the Sterilization of Native Reindeer Bone Morphogenetic Protein Extract

“…Ethylene oxide and gamma sterilization have been widely used to sterilize BMPs, but their effects on the osteoinductivity of BMPs have been under debate (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Ijiri et al (1994) reported that ethylene oxide sterilization at 29 C°for 5 hours decreased the osteoinductivity of native bovine BMP with collagen carrier to about half of the control values, but gamma irradiation (2.5 Mrad) decreased them even significantly more (13).…”

Irradiation has no effect on the incorporation of impacted morselized bone: A bone chamber study in goats

“…In some studies, irradiation has been found to inhibit (Buring and Urist 1967) or only partially destroy (Munting et al 1988, Schwarz et al 1988, Ijiri et al 1994, Zhang et al 1997) the osteoinductive capacity. In others, no effect of irradiation on the osteoinductive capacity has been found (Wientroub and Reddi 1988, Andriano et al 2000, Ripamonti et al 2000, Pekkarinen et al 2005.…”

“…These proteins may be released during the resorptive phase of bone graft incorporation, and can have a profound effect on bone cell physiology. Although studies have been performed to determine the effect of irradiation on BMPs (Munting et al 1988, Wientroub and Reddi 1988, Dziedzic-Goclawska et al 1991, Ijiri et al 1994, Andriano et al 2000, Ripamonti et al 2000, Pekkarinen et al 2005, the effect of irradiation on the incorporation process of morselized bone chips remains unclear. We studied the effects of steri-lization by gamma irradiation on the incorporation of impacted morselized allografts.…”

Influence of ethylene oxide sterilization on the activity of native reindeer bone morphogenetic protein

“…The sterilization of BMP before preclinical and clinical application is mandatory but problematic because BMPs do not tolerate heat management. Different sterilization methods, such as irradiation and chemical agents, have been tested [1,2,3,4,10,15,16,19,20,25]. Ethylene oxide (EO) gas sterilization, which is often used for medical devices [5], has been extensively used [2,3,4,10,15,16,19,20,25].…”