Stimulation of bone healing by transforming growth factor-beta 1 released from polymeric or ceramic implants.
The ability to transforming growth factor-beta 1 (TGF-beta 1), to stimulate bone healing was evaluated in a rat critical calvarial defect model.  Both a low dose and a high dose of TGF-beta 1 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 (CaSO 4).  Scanning electron microscopy showed that the CaSO 4 implants were more porous than the PLPG/DBM samples.  Both types of implants released biologically active TGF-beta 1 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-beta 1. 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 in the CaSO 4 implants containing a high dose of TGF-beta 1 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 CaSO 4 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-beta 1 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.
Gombotz
W R
WR
Biological Process Research, Bristol-Myers Squibb, Pharmaceutical Research Institute, Seattle, Washington.
Pankey
S C
SC
Bouchard
L S
LS
Phan
D H
DH
Puolakkainen
P A
PA
D000818:Animals; D001672:Biocompatible Materials; D001673:Biodegradation, Environmental; D001861:Bone Regeneration / Q000187:drug effects* / Q000502:physiology; D002133:Calcium Sulfate / Q000737:chemistry / Q000493:pharmacokinetics; D006133:Growth Substances / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics; D016062:Porosity; D019736:Prostheses and Implants; D011817:Rabbits; D017207:Rats, Sprague-Dawley; D014945:Wound Healing