Abstract

Magnetic Resonance Imaging (MRI) appears as a good surrogate to Computed Tomography (CT) scan as it does not involve radiation. In this context, a 3D anatomical and perfusion MR imaging protocol was developed to follow the evolution of bone regeneration and the neo-vascularization in femoral bone defects in rats. For this, three different biomaterials based on Pullulan-Dextran and containing either Fucoidan or HydroxyApatite or both were implanted. In vivo MRI, ex vivo micro-CT and histology were performed 1, 3 and 5 weeks after implantation. The high spatially resolved (156 × 182 × 195 µm) anatomical images showed a high contrast from the defects filled with biomaterials that decreased over time due to bone formation. The 3D Dynamic Contrast Enhanced (DCE) imaging with high temporal resolution (1 image/19 s) enabled to detect a modification in the Area-Under-The-Gadolinium-Curve over the weeks post implantation. The high sensitivity of MRI enabled to distinguish which biomaterial was the least efficient for bone regeneration, which was confirmed by micro-CT images and by a lower vessel density observed by histology. In conclusion, the methodology developed here highlights the efficiency of longitudinal MRI for tissue engineering as a routine small animal exam.

Highlights

  • To evaluate the outcomes of new biomaterials on bone regeneration and vascularization and compare their in vivo efficiencies, non-invasive imaging techniques are required

  • This polysaccharide–based matrix can be supplemented with another natural sulfated polysaccharide extracted from brown algae, fucoidan(noted Fuco thereafter), having an heparin-like structure and reported to modulate the heparin-binding angiogenic growth factor (FGF-2) activity and to induce angiogenesis in vitro[14,15,16]

  • For the defects filled with Matrix-HA and Matrix-HA-Fuco biomaterials, the hyper-intense signal disappeared over time, whereas the signal of the defect containing Matrix-Fuco remained even 5 weeks after implantation (Fig. 1a)

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Summary

Introduction

To evaluate the outcomes of new biomaterials on bone regeneration and vascularization and compare their in vivo efficiencies, non-invasive imaging techniques are required. Magnetic Resonance Imaging (MRI) appears as a non-invasive and non-ionizing technique well suited to in vivo longitudinal evaluation of tissue repair following a grafting procedure. This technique is a good candidate, both to visualize biomaterials within bones and to obtain functional data on the angiogenesis within the defect. Three different matrices were investigated for their properties in bone repair and vascularization: Matrix-Fuco, Matrix-HA, Matrix-HA-Fuco Both anatomical and functional MRI studies were performed to fully characterize the new tissue in 3D within the bone defect. Ex vivo micro-CT and histology were performed, in order to evaluate and quantify bone formation and compare the data from the different imaging modalities

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