Abstract
Longitudinal blood flow during murine bone graft healing was monitored non-invasively using diffuse correlation tomography. The system utilized spatially dense data from a scanning set-up, non-linear reconstruction, and micro-CT anatomical information. Weekly in vivo measurements were performed. Blood flow changes in autografts, which heal successfully, were localized to graft regions and consistent across mice. Poor healing allografts showed heterogeneous blood flow elevation and high inter-subject variabilities. Allografts with tissue-engineered periosteum showed responses intermediate to both autografts and allografts, consistent with healing observed. These findings suggest that spatiotemporal blood flow changes can be utilized to differentiate the degree of bone graft healing.
Highlights
Critical-sized bone defects cannot heal without intervention [1]
The average αDb value within the anomaly from the non-linear reconstruction is lower than the expected value and the high αDb region disperses beyond the expected z range (1.25 – 2.75 mm)
Our system enabled the collection of spatially dense data with multiple source-detector separations for 3D imaging reconstruction, utilized a non-linear reconstruction approach to improve the accuracy in the reconstruction and leveraged the anatomical structure of each mouse obtained with micro-computed tomography (CT) to define the geometry and optical properties
Summary
Critical-sized bone defects cannot heal without intervention [1]. More than 500,000 U.S and 2.2 million global orthopedic procedures are carried out to treat critical-sized bone defects [2, 3]. Among those procedures, autograft transplantation utilizes healthy endogenous bone and soft tissue from a non-load bearing region of the skeleton. Allografts are completely devitalized, during which the periosteum, a thin tissue layer covering the outer bone surface, which is important for complete bone healing [6], is lost. To assess the effectiveness of allografts augmented with tissue engineered periostea, a murine segmental femoral defect model (graft model) is often used in pre-clinical studies. The healing outcome and the physiological changes during healing are assessed, such as graft vascularization, bone callus formation and bone strength [5]
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