A biodegradable polymer scaffold for delivery of osteotropic factors

Despite discoveries and developments in osteotropic factors, therapies expl oiting these macromolecules have been Limited due to a lack of suitable del ivery vehicles and three dimensional (3D) scaffolds that promote bone regen eration. To address this limitation, an emulsion freeze-drying process was developed to fabricate biodegradable scaffolds with controlled microarchite cture, and the ability to incorporate and deliver bioactive macromolecules for bone regeneration. The effect of median pore size and protein loading o n protein release kinetics was investigated using scaffolds with different protein loading and median pore sizes ranging from 7 to 70 mu m. Graphs of protein release from scaffolds showed an initial burst followed by a slower sustained release. Release kinetics were characterized using an unsteady-s tate, diffusion-controlled model with an effective diffusivity that took to rtuosity (tau) and partition coefficient for protein adsorption (K-p) onto the scaffold walls into account. Tortuosity and partition coefficient signi ficantly reduced the protein diffusivity by a factor of 41 +/- 43 and 105 /- 51 for 60 and 30-mu m median pore-sized scaffolds, respectively. The act ivity of the protein released from these scaffolds was demonstrated by deli vering rhBMP 2 and [A-4] (an amelogenin derived polypeptide) proteins from the scaffold and regenerating bone in a rat ectopic bone induction assay [W hang et al. J Biomed Mater Res 1998;42:491-9, Veis et al. J Bone Mineral Re s, Submitted]. (C) 2000 Published by Elsevier Science Ltd.