Alteration of blood clot structures by interleukin-1 beta in association with bone defects healing.

Xin Wang,Paul P Masci,Wenbo Liao,Thor E Friis,Ross W Crawford,Yin Xiao

doi:10.1038/srep35645

Abstract

The quality of hematomas are crucial for successful early bone defect healing, as the structure of fibrin clots can significantly influence the infiltration of cells, necessary for bone regeneration, from adjacent tissues into the fibrin network. This study investigated if there were structural differences between hematomas from normal and delayed healing bone defects and whether such differences were linked to changes in the expression of IL-1β. Using a bone defect model in rats, we found that the hematomas in the delayed healing model had thinner fibers and denser clot structures. Moreover, IL-1β protein levels were significantly higher in the delayed healing hematomas. The effects of IL-1β on the structural properties of human whole blood clots were evaluated by thrombelastograph (TEG), scanning electronic microscopy (SEM), compressive study, and thrombolytic assays. S-nitrosoglutathione (GSNO) was applied to modulate de novo hematoma structure and the impact on bone healing was evaluated in the delayed healing model. We found that GSNO produced more porous hematomas with thicker fibers and resulted in significantly enhanced bone healing. This study demonstrated that IL-1β and GSNO had opposing effects on clot architecture, the structure of which plays a pivotal role in early bone healing.

Highlights

A hematoma made up of platelets and fibrin fibers forms at the bone fracture sites to minimize bleeding[13]
We have investigated whether IL-1βexerts a regulatory function on fibrin polymerization and whether, by altering the hematoma structure with GSNO, it is possible to speed up bone regeneration in large bone defects
Bone graft materials available have been used to improve bone regeneration, but many are fraught with complications, such as foreign body reaction, which results in fibrotic encapsulation[25]

Summary

Introduction

A hematoma made up of platelets and fibrin fibers forms at the bone fracture sites to minimize bleeding[13]. Activation and subsequent aggregation of platelets leads to the secretion of cytokines and chemokines which regulate hemostasis. This process directly influences fibrin clot architecture and affects the subsequent reparative process[14,15]. We have investigated whether IL-1βexerts a regulatory function on fibrin polymerization and whether, by altering the hematoma structure with GSNO, it is possible to speed up bone regeneration in large bone defects. Altering the physical structure of the hematoma by means of biological agents such as GSNO may prove to be a valid therapeutic approach to augment recalcitrant bone fractures

Methods

Results

Conclusion