CONTROLLED-RELEASE OF TGF-BETA(1) FROM A BIODEGRADABLE MATRIX FOR BONE REGENERATION

Although bone has a remarkable capacity for regenerative growth, there are many clinical situations in which the bony repair process is impa ired. TGF-beta1 is a 25 kD homodimeric protein which modulates the gro wth and differentiation of many cell types. The ability of TGF-beta1 t o promote bone formation suggests that it may have potential as a ther apeutic agent in disease of bone loss. However, there still exists a n eed for an effective method of delivering TGF-beta1 to the site of an osseous defect for the promotion of bone healing. This paper describes a novel biodegradable controlled release system for TGF-beta1 compris ed of poly (DL-lactic-co-glycolic acid) (PLPG) and demineralized bone matrix (DBM). The amount and activity of TGF-beta1 released was determ ined using several methods including I-125-labeled TGF-beta1 as a trac er, an enzyme linked immunosorbent assay (ELISA) and a growth inhibito ry assay (GIA). Protein was released from the devices for time periods of more than 600 h. The amount of TGF-beta1 released was directly pro portional to both the TGF-beta1 loading and the weight percent of DBM in the device. The release kinetics could be further controlled by app lying polymeric coatings of varying porosity to the devices. The GIA i ndicated that between 80 and 90% of the TGF-beta1 released from the de livery system retained its bioactivity. The PLPG and DBM existed in ph ase separated domains within the device as determined by differential scanning calorimetry. Scanning electron microscopy suggested that the devices were sufficiently porous to allow bone ingrowth.