Quantifying 3D Strain in Scaffold Implants for Regenerative Medicine

Abstract

Regenerative medicine solutions require thoughtful design to elicit the intended biological response. This includes the biomechanical stimulus to generate an appropriate strain in the scaffold and surrounding tissue to drive cell lineage to the desired tissue. To provide appropriate strain on a local level, new generations of scaffolds often involve anisotropic spatially graded mechanical properties that cannot be characterised with traditional materials testing equipment. Volumetric examination is possible with three-dimensional (3D) imaging, in situ loading and digital volume correlation (DVC). Micro-CT and DVC were utilised in this study on two sizes of 3D-printed inorganic/organic hybrid scaffolds (n = 2 and n = 4) with a repeating homogenous structure intended for cartilage regeneration. Deformation was observed with a spatial resolution of under 200 µm whilst maintaining displacement random errors of 0.97 µm, strain systematic errors of 0.17% and strain random errors of 0.031%. Digital image correlation (DIC) provided an analysis of the external surfaces whilst DVC enabled localised strain concentrations to be examined throughout the full 3D volume. Strain values derived using DVC correlated well against manually calculated ground-truth measurements (R2 = 0.98, n = 8). The technique ensures the full 3D micro-mechanical environment experienced by cells is intimately considered, enabling future studies to further examine scaffold designs for regenerative medicine.

In Vivo Deformation and Strain Measurements in Human Bone Using Digital Volume Correlation (DVC) and 3T Clinical MRI

“…Moreover, based on zero-strain test results implementing a multi-pass scheme is not suggested for this application, as the multi-pass scheme did not improve the strain measurement errors, and even increased the errors by 15% compared to the single-pass scheme when using the FFT + DC approach. In line with previous DVC studies performed on microCT [ 26 , 32 , 43 , 44 , 55 ], SR-microCT [ 28 , 36 ], and microMRI [ 42 ], strain errors decreased with increasing subset size following a power law relationship. However, it should be noted that increasing the subset size reduces the spatial resolution.…”

“…A limitation of this study was that the DVC uncertainties were calculated in a homogeneous zero-strain condition provided by repeated scans. Zero-strain tests can be used to investigate the noise within a system and is an established method to quantify the DVC errors for different applications [ 26 , 28 , 32 , 33 , 37 , 38 , 41 , 42 , 43 , 44 ]. A zero-strain test also provides a standard protocol that allows a comparison of DVC uncertainties for different imaging modalities, mathematical approaches, and biological tissues.…”

“…DVC was conducted using DaVis 8.4 software (LaVision Ltd., Goettingen, Germany). To optimise DVC settings, three DVC algorithms were implemented in this study: Fast Fourier Transform (FFT) [ 15 , 26 ], Direct Correlation (DC) [ 27 , 28 , 32 ], and a combination of FFT and DC (FFT + DC) [ 42 , 43 , 44 , 50 ]. In all algorithms, the measurement volume was divided into smaller sub-volumes (called subsets) and the contrast patterns within the subsets were then tracked from the first volume (reference) into the second volume [ 51 ].…”

“…This method uses the FFT approach for an initial prediction of large displacements, which are then refined using the DC approach. This approach was initially used to identify the optimal MRI sequence (subset size of 44 voxels), since previous studies [ 42 , 43 , 44 ] showed that FFT + DC has lower errors compared to the FFT and DC approaches for bone, cartilage and intervertebral discs. After identifying the optimal sequence, all DVC approaches were applied to it in order to quantify errors of each approach for different subset sizes.…”

“…When exploring new applications of DVC, it is important to evaluate the uncertainties associated with the technique. A zero-strain test is a widely used technique to quantify uncertainties of DVC measured displacements and strains on an object that has been strained a known amount (zero-strain) [ 26 , 28 , 32 , 33 , 37 , 38 , 41 , 42 , 43 , 44 ]. Therefore, the main aim of this study was to use DVC in combination with 3T clinical MRI for the first time to assess its potential to evaluate deformations and strains in human bones in vivo.…”