Abstract

Introduction The evaluation of novel synthetic bone implants relies mostly on histological examination, but as bone repair takes several weeks, non-invasive imaging techniques have gained interest in the recent past. Ιn the frame of this study, we establish a SPECT/CT imaging protocol for the longitudinal assessment of bone healing of a calvarial mouse defect model using mineralized collagen-based scaffolds. Materials and Methods Two symmetrical calvarial bone defects, 1.5 mm in diameter each, were created in female Swiss mice. Gaps were monitored weekly through SPECT/CT imaging (γ-CUBE, X-CUBE, Molecubes, providing a resolution of 0.6 mm and 0.05 mm, respectively), using [99mTc]-MDP for 5 weeks. Defects created on the left part of the mouse skull were left unfilled (control group), whereas those on the right part were filled with mineralized horse collagen scaffold materials (HA/Coll). Results and Discussion: The monitoring of bone healing was successfully and accurately performed via SPECT/CT imaging. CT imaging showed the actual bone filling process and the formation of new bone tissue, whereas SPECT imaging provided the increased metabolic activity. For the HA/Coll treated defect, a peak in metabolic activity was noted at week 1 post-surgery and the defect was filled by newly developed bone tissue by week 3 post-surgery (Figure 1). In contrast, the metabolic activity at the control defect area was stable but significantly lower and a complete healing was not observed even up to week 5post-surgery. These results show that combined SPECT/CT imaging can provide an accurate tool for bone healing monitoring. CT is a high resolution tool for new bone formation control and SPECT is a high sensitivity tool for early metabolic activity confirmation, also having a high prognostic value for bone healing. Conclusions SPECT revealed the earliest signs of new bone tissue formation due to the increased metabolic activity and CT provided a clear visualization and quantification ability of the healing process over time. This study is part of the EU Horizon 2020 research and innovation VIVOIMAG project under the Marie Skłodowska-Curie grant agreement No 645757. This study was co-supported through the Programme of Industrial Scholarships of Stavros Niarchos Foundation. Figure 1. Indicative axial CT (a), sagittal SPECT/CT (b) and axial SPECT/CT (c) at 3 h [99m]Tc-MDP post-injection (~2 mCi) of a bilateral calvarial mouse defect treated (HA/Coll) and non-treated (control), at week 1 (first row) and at week 3 (second row) post-surgery.

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