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Synergistic effect of IGF-I and TGF-ß1 on fracture
healing in rats Single versus combined application of IGF-I and TGF-ß1 Gerhard Schmidmaier, Britt Wildemann, Tobias Gäbelein, Joanna Heeger, Frank Kandziora, Norbert P Haas and Michael Raschke Department of Trauma and Reconstructive Surgery, Charité, Humboldt-University of Berlin, Germany Correspondence: gerhard.schmidmaier@charite.de Submitted 02-04-10. Accepted 02-11-16 ABSTRACT During the last few decades, knowledge about growth factors and their function has increased. However, little is known about the interaction of these factors during bone growth and fracture healing. In vitro studies have shown a higher rate of cell proliferation and cell metabolism after the use of IGF-I and TGF-ß1 in combination, as compared to the single use of these factors. The purpose of this study was to investigate a possible synergistic effect of these growth factors in vivo, using a fracture model. A midshaft fracture of rat tibia (n = 84) was intramedullary stabilized with poly(D,L-lactide)-coated or uncoated titanium K-wires. The growth factors IGF-I and TGF-ß1, singly or in combination, were incorporated in the coating and continuously released during fracture healing. 28 days after fracture, we performed mechanical tests and histomorphological analyses. We found a greater stimulating effect of IGF-I on fracture healing than of TGF-ß1. The combined application of both growth factors resulted in a significantly higher maximum load and torsional stiffness than the use of only one of them. The histomorphometric analyses showed an increase in remodeling of the fracture callus in this group with less cartilaginous and more mineralized tissue than in the other groups. Both growth factors seem to have a synergistic effect on fracture healing in this model. Increasing evidence indicates that growth factors, such as insulin-like growth factor (IGF) or transforming growth factor-beta (TGF-ß), are important regulators of cellular proliferation, differentiation, extracellular matrix synthesis and mineralization (Mohan and Baylink 1991, Linkhart et al. 1996, Trippel et al. 1996, Lind 1998). TGF-ß1 is expressed at high levels in osteoblasts during bone development (Kim and Ballock 1993) and healing (Joyce et al. 1990a, Steinbrech et al. 2000, Tatsuyama et al. 2000). It affects cell proliferation and phenotypic gene expression in vitro (Hock et al. 1990, Centrella et al. 1991) and stimulates bone healing in vivo (Gombotz et al. 1994, Fujimoto et al. 1999). IGF-I stimulates the replication of osteoblasts and the synthesis of bone matrix in vitro (Canalis 1980, Hock et al. 1988) and healing of bone defects in vivo (Thaller et al. 1993a). The use of these factors individually or in combination stimulates cell proliferation and cell metabolism. A synergistic effect of IGF-I and TGF-ß1 on cell proliferation, matrix synthesis and differentiation was seen in chondrocyte cell culture (Tsukazaki et al. 1994, Matsumura et al. 2000). Similar results have been reported concerning the effects on proliferation and differentiation of osteoblasts (Kasperk et al. 1990). We studied the effects of the growth factors IGF-I and TGF-ß1 on fracture healing when applied locally alone or together. The tibiae of rats were fractured in a standardized manner and the progress of healing was evaluated radigraphically. After 28 days, mechanical torsional testing and histomorphometric analyses were done. I used it when I had a bone graft on my jaw and that healed nicely.
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SYL: what kind of dosage did you use for your jaw? Do you think it matters where I inject?
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I would say 50mcg is a good all-around dose. Injecting it as close to the injury as possible would provide the best benefit.
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Update:
Worked VERY well. Used 1 vial. Doc was impressed, xrays showing very good healing. You'll see peptides; specifically FGF-2, being used in the future to facillitate fracture healing. |
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Thanks for the update!
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