Bone defect repair in rat tibia by TGF-β1 and IGF-1 released from hydrogel scaffold

Abstract

Bone repair is one of the major challenges facing reconstructive surgery. Bone regeneration is needed for the repair of large defects and fractures. The ability of TGF-beta1 and IGF-1 incorporated into hydrogel scaffold to induce bone regeneration was evaluated in a rat tibia segmental defect model. External fixation was performed prior to the induction of the segmental bone defect in order to stabilize the defect site. Hydrogel scaffold containing either TGF-beta, IGF-1, TGF-beta + IGF-1, hydrogel containing saline or saline, were inserted in the defect. Calcified material was observed in the defects treated with TGF-beta 2 weeks following the start of treatment. Bone defects treated with TGF-beta, IGF-1 or TGF-beta + IGF-1 revealed significant bone formation after 4 and 6 weeks when compared to the control specimens. X-ray images showed that solid bone was present at the defect site after 6 weeks of treatment with TGF-beta or TGF-beta + IGF-1. A less pronounced bone induction was observed in the control specimens and bones treated with IGF-1. Percent closure ratio of bone defects after 6 weeks were 40, 80, 89, and 97% for saline, hydrogel, IGF-1, TGF-beta and IGF-1 + TGF-beta groups, respectively. It is concluded that hydrogel scaffold can serve as a good osteoconductive matrix for growth factors, and that it provides a site for bone regeneration and enhances bone defect healing and could be used as alternative graft material.

Growth Factor Interactions in Bone Regeneration

“…Unfortunately, few studies compared the growth factor combination versus single IGF and TGF-b controls and their experimental setup varied greatly, in particular with respect to dose and delivery vehicle (Table 4). [85][86][87][88] Compared to TGF-b alone, nanogram dosages of the IGF/TGF-b combination in solution or released from gelatin hydrogels did not result in significantly enhanced mechanical properties or bone formation in rat marginal cortical defects, tibial defects, and mandibular defects, but the release of micrograms of the growth factor combination from a coated titanium implant enhanced the mechanical properties and callus formation in a rat tibial fracture model (Table 4).…”

A Perspective: Engineering Periosteum for Structural Bone Graft Healing

“…The most notable ones are the bone morphogenic proteins (BMPs) that belong to the transforming growth factor beta superfamily, Hedgehog proteins, and Wnt proteins. Others include fibroblast growth factors (FGFs) and insulinlike growth factors (IGFs), which have positive effects on bone healing [44,55,83]. BMP-2 expression occurred in early periosteal callus just a few days after cortical bone fracture [11].…”

Small Molecule Inhibition of Transforming Growth Factor Beta Signaling Enables the Endogenous Regenerative Potential of the Mammalian Calvarium

“…22,23 Studies on several in vivo bone repair models have also provided evidence for a proosteogenic role for TGFb. [24][25][26][27] Conversely, in immature cells, TGFb has an inhibitory effect. Alliston et al reported that TGFb inhibits osteoblast differentiation through Smad3-mediated suppression of Runx2 function and expression.…”