Stimulation of bone healing by transforming growth factor-beta1 released from polymeric or ceramic implants

The ability of transforming growth factor‐beta1 (TGF‐β1) to stimulate bone healing was evaluated in a rat critical calvarial defect model. Both a low dose and a high dose of TGF‐β1 were incorporated into two different types of implants: one made from a composite of poly(lactic‐co‐glycolic acid) (PLPG) (50:50) and demineralized bone matrix (DBM), and the other from calcium sulfate (CaSO4). Scanning electron microscopy showed that the CaSO4 implants were more porous than the PLPG/DBM samples. Both types of implants released biologically active TGF‐β1 for over 300 h in vitro. The samples were implanted in a 9‐mm diameter rat calvarial defect for 6 weeks along with contralateral control implants containing no TGF‐β1. Microradiography and histological analysis were used to assess the bone healing in the defects. Microradiography revealed that the greatest amount of calcified bone (67.5%) was present in the CaSO4 implants containing a high dose of TGF‐β1 while minimal new bone formation occurred in the PLPG/DBM implants. Histologically, the PLPG/DBM implants exhibited an inflammatory response with little mineralization or bone formation. The defects containing the PLPG/DBM implants consisted of a connective tissue stroma with large void spaces. Giant cells and numerous polymorphonuclear leukocytes were present throughout the implants. In contrast, the CaSO4 implants had only a few inflammatory cells and the presence of mineralization and true bone was a more consistent feature. These preliminary studies show that TGF‐β1 is capable of inducing new bone formation. Furthermore, the materials used to deliver the growth factor can play a significant role in the bone healing process. © 1994 John Wiley & Sons, Inc.