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Open Access Research article

Thrombin related peptide TP508 promoted fracture repair in a mouse high energy fracture model

Brain M Hanratty1, James T Ryaby2, Xiao-Hua Pan3 and Gang Li14*

Author Affiliations

1 Department of Orthopaedic Surgery, School of Biomedical Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7B, UK

2 Research and Development, OrthoLogic Corp, 1275 West Washington Street, Tempe, AZ, USA

3 Department of Orthopaedic Surgery, People's Hospital of Shenzhen City, Shenzhen, PR China

4 Department of Orthopaedics & Traumatology, The Chinese University Hong Kong, Clinical Sciences Building, Prince of Wales Hospital, Shatin, Hong Kong, PR China

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Journal of Orthopaedic Surgery and Research 2009, 4:1  doi:10.1186/1749-799X-4-1

Published: 29 January 2009

Abstract

Background

Thrombin related peptide (TP508) is a 23 amino-acid synthetic peptide that represents a portion of the receptor-binding domain of thrombin molecule. Previous studies have shown that TP508 can accelerate musculoskeletal tissue repair including fracture healing.

Objectives

The aim of this study was to investigate the effect of TP508 on fracture healing in a murine fracture model representing high energy fracture situation.

Methods

Eighty CD 1 mice underwent controlled quadriceps muscle crush and open transverse mid diaphyseal femoral fracture that was then fixed with an external fixator. Animals were randomised into four groups to receive an intra-operative dose of either 100 μg TP508 into the fracture gap; 100 μg TP508 into the surrounding damaged muscle tissues; 10 μg TP508 into the fracture gap, or control equal amount of saline into the fracture gap. Radiographic assessment was performed weekly for 5 weeks; histological analysis was at 3 and 5 weeks post fracture and biomechanical testing of the fractured bone was performed at 5 weeks post fracture.

Results

Mechanical testing data showed that the fracture stiffness was significantly higher in the group receiving 100 μg TP508 into the fracture gap than other groups. Histological and radiographic analysis revealed a trend of increase in bone formation in the 100 μg TP508 injected into the fracture gap group compared to the saline control group. It was noted that the scar tissues was significantly less in Group II comparing with the saline control group and there was increased blood vessel formation in the crushed muscles and fracture gap areas in the groups receiving TP508 comparing to the saline control group.

Conclusion

The results from this study demonstrated the use of thrombin related peptide TP508 in the situation of a high energy fracture can promote fracture healing and reduce the potential complications such as muscle fibrosis and fracture delayed or non-union.