Thrombin peptide (TP508) promotes fracture repair by up-regulating inflammatory mediators, early growth factors, and increasing angiogenesis

Abstract

Previous studies have shown that a single injection of thrombin peptide (TP508) accelerates fracture repair in a closed rat femoral fracture model. The present study was conducted to elucidate the molecular mechanisms of TP508 action using Affymetrix genomescale profiling and to link early gene expression changes to fracture histology and bone strength changes. Treatment of femoral fractures with TP508 accelerated fracture repair as determined by destructive torsion testing. Blinded histological analysis demonstrated that TP508-treated fracture callus had a significant increase in blood vessels relative to the controls. Gene array analysis showed that TP508 significantly induced expression of early growth factors, inflammatory response modifiers, and angiogenesis-related genes. This study therefore suggests that TP508 promotes fracture repair through a mechanism that involves an increased induction of a number of growth factors, enhanced expression of inflammatory mediators, and angiogenesis-related genes.

Alkali treatment of microrough titanium surfaces affects macrophage/monocyte adhesion, platelet activation and architecture of blood clot formation

“…Thrombin, e.g., plays a key role for leukocyte and platelet activation and induces the formation of a fi brin matrix, which allows cell invasion and acts as a sustained release system for secreted cytokines and mitogens (Brass, 2003;Mosesson, 2005). Additionally, direct stimulatory potential of thrombin on osteogenesis has been reported (Karp et al, 2005;Li et al, 2005;Song et al, 2005;Wang et al, 2005;Pagel et al, 2006;Pagel et al, 2009 ). This strong relation between the activation of blood coagulation, acute infl ammation and osteogenesis suggests that thrombogenesis provides important stimuli for osseointegration of endosseous implants (Stanford, 2010).…”

Harnessing and Modulating Inflammation in Strategies for Bone Regeneration

“…100 This peptide has been shown to be a very potent stimulator of in vivo bone regeneration, with a single injection into a rat femoral fracture increasing the strength of the healed bone by over 30%. 101 In rabbit models, TP508 has been shown to stimulate bone regeneration of critical-sized defects when incorporated into a PLGA microparticle-based controlled release system. 102,103 However, in a recent Phase III clinical trial of this agent, a single injection of TP508 into the site of a radius fracture failed to significantly improve (vs. placebo) the primary measure of success, which was the total time that the fracture required immobilization.…”

Nanotechnology applications in osteodistraction

“…[56] Another procedure to accelerate bone regeneration involves the application of osteogenic proteins in the distraction gap using nanotechnology-fabricated drug-release systems. [57] Much research effort has been committed to the investigation of ordered mesoporous silica materials in the biomedical field for two main reasons: their ability to regenerate bone tissue [58] and their drug delivery possibilities. [59] When these silica-based ordered mesoporous materials are exposed to the physiological environment, a series of chemical reactions take place in the material-living tissue interface, which lead to incorporation of the material into the living tissue.…”