Plastic Surgery Research Council
Members Only  |  Contact  |  PSRC on Facebook

Back to Annual Meeting Program


CONTROLLED REPAIR OF A RABBIT CRANIAL DEFECT BY SUSTAINED DELIVERY OF LOW-DOSE BONE MORPHOGENETIC PROTEIN-2 (BMP2) ENCAPSULATED IN PLGA MICROSPHERES
Presenter: Jason D Wink, BA
Co-Authors: Gerety PA; Sherif R; McGrath JL; Clarke NA; Nah HD; Taylor JA
Perelman School of Medicine at the University of Pennsylvania

The use of BMP2 has seen significant growth in recent years. Side effects including heterotopic ossification (HO) and inflammation have precluded its use in areas requiring fine control over osteogenesis. These are thought to be secondary to a high dose of free BMP2 (frBMP) and a bolus delivery system. We hypothesized that sustained delivery will allow for a lower dose of BMP2 required for osteo-induction. 15% Poly(lactic-co-glycolic acid) microspheres encapsulating BMP2 (BMP-MS) were prepared, using a double emulsion solvent extraction/evaporation technique. Protein loading efficiency, release kinetics, and post-encapsulation bioactivity of BMP2 were determined using in vitro assays. Sustained vs. bolus delivery was then studied in vivo utilizing a 10mm rabbit cranial defect model. Cellular and acellular experimental groups included BMP-MS, frBMP, scaffold only and empty control. Volume (V) and surface area (SA) analysis for newly formed bone was performed using MicroCT. Histology was performed with H&E and Trichrome staining. Statistical significance was determined by nonparametric analysis, Pearson correlation and chi2 analysis (p<.05). BMP-MS (0.1ug/defect) induced new bone formation at 45.38+/-8.41% of the initial bony volume and 126.57+/-13.84% of surface area, outperforming the 0.1 ug frBMP/defect group (p=.049, .049). No significant difference was found between all cellular groups (V p=.38, SA p=.86). BMP-MS outperformed the BMSC+ BMP-MS group, but only reached statistical significance for surface area (p=.033). No significant difference was found with the use of ASC instead of BMSC (V p=.77, SA p= .38). The incidence of heterotopic ossification was minimal with both cellular BMP-MS groups (25%, p= .10) compared to all other experimental groups. Correlation coefficient between surface area and volume equaled .79. Our results indicate that a sustained BMP2 delivery system using PLGA-MS allows for a significantly reduced effective dose and minimizes the incidence of heterotopic ossification. We also showed that inclusion of allogeneic BMSCs did not improve new bone formation.


Back to Annual Meeting Program