Controlled release of an osteogenic peptide from injectable biodegradable polymeric composites

Poly(D,L-lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) blend microparticles loaded with the osteogenic peptide TP508 were added to a mixture of poly(propylene fumarate) (PPF), poly(propylene fumarate)-diacrylate (PPF-DA), and sodium chloride (NaCl) for the fabrication of PPF composite scaffolds that could allow for tissue ingrowth as well as for the controlled release of TP508 when implanted in an orthopedic defect site. In this study, PPF composites were fabricated and the in vitro release kinetics of TP508 were determined. TP508 loading within the PLGA/PEG microparticles, PEG content within the PLGA/PEG microparticles, the microparticle content of the PPF composite polymer component, and the leachable porogen initial mass percent of the PPF composites were varied according to a fractional factorial design and the effect of each variable on the release kinetics was determined for up to 28 days. Each composite formulation released TP508 with a unique release profile. The initial release (release through day 1) of the PLGA/PEG microparticles was reduced upon inclusion in the PPF composite formulations. Day I normalized cumulative mass release from PPF composites ranged from 0.14 +/- .01 to 0.41 +/- 0.01, whereas the release from PLGA/PEG microparticles ranged from 0.31 +/- 0.02 to 0.58 +/- 0.01. After 28 days, PPF composites released 53 +/- 4% to 86 +/- 2% of the entrapped peptide resulting in cumulative mass releases ranging from 0.14 +/- 0.01 mug TP508/mm(3) scaffold to 2.46 +/- 0.05 mug TP508/mm(3) scaffold. The results presented here demonstrate that PPF composites can be used for the controlled release of TP508 and that alterations in the composite's composition can lead to modulation of the TP508 release kinetics. These composites can be used to explore the effects varied release kinetics and dosages on the formation of bone in vivo. (C) 2002 Elsevier Science B.V. All rights reserved.