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Tozzi, G.

Publications and source records attributed to Tozzi, G..

5 recordsLinked to original sources

Data-driven image mechanics (D2IM): a deep learning approach to predict displacement and strain fields from undeformed X-ray tomography images - Evaluation of bone mechanics.

Experimental measurement of displacement and strain fields using techniques such as digital volume correlation (DVC) from in situ X-ray computed tomography (XCT) has notably advanced the understanding of bone mechanics from organ to tissue level. Being experimental in nature, DVC output has been often employed to validate finite element (FE) models of bone improving their predictive ability. Despite the excellent results achieved, these techniques are complex, time consuming, potentially affecting tissue mechanical properties, and their predictive ability requiring prior knowledge of material properties. The recent advent of deep learning (DL) has enabled data-driven models, paving the way for the full exploitation of rich image datasets from which physics can be learnt and retained. Here we propose a novel data-driven image mechanics (D2IM) approach based on feed forward convolutional neural network (CNN) that learns from DVC displacement fields of vertebrae, predicting displacement and strain fields for undeformed XCT images. D2IM successfully predicted all displacement fields, particularly the one for the z loading axis (w), where high correlation (R2=0.93) and minimal error (as low as less than 1m) were found when comparing measured against predicted displacements. The predicted axial strain field in z ({varepsilon}zz) was also consistent in distribution with the measured one, displaying generally reduced errors (as low as few tens of {varepsilon}) in the regions within the vertebral body where the effect of border outliers was minimal. This is the first study using experimental full-field measurements on bone structures from DVC to inform DL-based model such as D2IM, which represents a major contribution in the prediction of displacement and strain fields only based on the greyscale content of undeformed XCT images. The future development of D2IM will incorporate a wider range of structures and loading scenarios for accurate prediction of physical fields in both hard and soft tissues, aiming at clinical translation for improved diagnostics.

bioengineering↗

Full-field strain distribution in hierarchical electrospun nanofibrous Poly-L(lactic) acid and Collagen based scaffolds for tendon and ligament tissue regeneration: a multiscale study

Regeneration of injured tendons and ligaments (T/L) is a worldwide need. In this study electrospun hierarchical scaffolds made of a poly (L-lactic) acid and collagen blend were developed reproducing all the multiscale levels of aggregation of these tissues. Scanning electron microscopy, microCT and tensile mechanical tests were carried out, including a multiscale digital volume correlation analysis to measure the full-field strain distribution of electrospun structures. The principal tensile and compressive strains detected the pattern of strains caused by the nanofibers rearrangement, while the deviatoric strains revealed the related internal sliding of nanofibers and bundles. The results of this study confirmed the biomimicry of such electrospun hierarchical scaffolds, paving the way to further tissue engineering and clinical applications. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=92 SRC="FIGDIR/small/543145v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1a67baorg.highwire.dtl.DTLVardef@190149aorg.highwire.dtl.DTLVardef@38968borg.highwire.dtl.DTLVardef@123bb49_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

Biofabrication of nanocomposite-based scaffolds containing human bone extracellular matrix for the differentiation of skeletal stem and progenitor cells

Autograft or metal implants are routinely used in skeletal repair but can fail to provide a long-term clinical resolution, emphasising the need for a functional biomimetic tissue engineering alternative. An attractive sustainable opportunity for tissue regeneration would be the application of human bone waste tissue for the synthesis of a material ink for 3D bioprinting of skeletal tissue. The use of human bone extracellular matrix (bone-ECM) offers an exciting potential for the development of an appropriate micro-environment for human bone marrow stromal cells (HBMSCs) to proliferate and differentiate along the osteogenic lineage. Extrusion-based deposition was mediated by the blending of human bone-ECM (B) with nanoclay (L, Laponite(R)) and alginate (A) polymer, to engineer a novel material ink (LAB). The inclusion of nanofiller and polymeric material increased the rheological, printability, and drug retention properties and, critically, the preservation of HBMSCs viability upon printing. The composite human bone-ECM-based 3D constructs containing vascular endothelial growth factor (VEGF) enhanced vascularisation following implantation in an ex vivo chick chorioallantoic membrane (CAM) model. Addition of bone morphogenetic protein-2 (BMP-2) with HBMSCs further enhanced vascularisation together with mineralisation after only 7 days. The current study demonstrates the synergistic combination of nanoclay with biomimetic materials, (alginate and bone-ECM) to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalised skeletal tissue repair. Graphical AbstractEngineering nanoclay-based bone ECM novel bioink for bone regeneration. Human bone trabecular tissue was demineralised, decellularised and blended with nanoclay (Laponite(R)) and alginate after digestion. The resulting ink was investigated for printability following rheological and filament fusion investigation. The microstructural arrangement of the blends was examined together with viability and functionality of bioprinted HBMSCs. Finally, the ability of the novel blend to support drug release ex vivo in a CAM model was determined confirming the potential of the bone ECM ink to support bone formation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=191 SRC="FIGDIR/small/536074v1_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@b9dc13org.highwire.dtl.DTLVardef@1f6f0dorg.highwire.dtl.DTLVardef@1b3c098org.highwire.dtl.DTLVardef@295192_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

Nonlinear micro finite element models based on digital volume correlation measurements predict early microdamage in newly formed bone

Bone regeneration in critical-sized defects is a clinical challenge, with biomaterials under constant development aiming at enhancing the natural bone healing process. The delivery of bone morphogenetic proteins (BMPs) in appropriate carriers represents a promising strategy for bone defect treatment but optimisation of the spatial-temporal release is still needed for the regeneration of bone with biological, structural, and mechanical properties comparable to the native tissue. Nonlinear micro finite element (FE) models can address some of these challenges by providing a tool able to predict the biomechanical strength and microdamage onset in newly formed bone when subjected to physiological or supraphysiological loads. Yet, these models need to be validated against experimental data. In this study, experimental local displacements in newly formed bone induced by osteoinductive biomaterials subjected to in situ X-ray computed tomography compression in the apparent elastic regime and measured using digital volume correlation (DVC) were used to validate FE models. Displacement predictions from homogeneous linear FE models were highly correlated to DVC-measured local displacements, while tissue heterogeneity capturing mineralisation differences showed negligible effects. Nonlinear FE models improved the correlation and showed that tissue microdamage occurs at low apparent strains. Microdamage seemed to occur next to large cavities or in biomaterial-induced thin trabeculae, independent of the mineralisation. While localisation of plastic strain accumulation was similar, the amount of damage accumulated in these locations was slightly higher when including material heterogeneity. These results demonstrate the ability of the nonlinear FE model to capture local microdamage in newly formed bone tissue and can be exploited to improve the current understanding of healing bone and mechanical competence. This will ultimately aid the development of BMPs delivery systems for bone defect treatment able to regenerate bone with optimal biological, mechanical, and structural properties.

bioengineering↗

Fibrillar-Level Strain Gradients Across the Calcified Bone-Cartilage Interface

The bone-cartilage unit (BCU) is a universal feature in diarthrodial joints, which is mechanically-graded and subjected to shear and compressive strains. Changes in the BCU have been linked to osteoarthritis progression. Here we report existence of a physiological internal strain gradient (pre-strain) across the BCU at the ultrastructural scale of the extracellular matrix constituents, specifically the collagen fibril. We use X-ray scattering that probes changes in the axial periodicity of fibril-level D-stagger of tropocollagen molecules in the matrix fibrils, as a measure of microscopic pre-strain. We find that mineralized collagen nanofibrils in the calcified plate are in tensile pre-strain relative to the underlying trabecular bone. This behaviour contrasts with the previously accepted notion that fibrillar pre-strain (or D-stagger) in collagenous tissues always reduces with mineralization, via reduced hydration and associated swelling pressure. Within the calcified part of the BCU, a finer-scale gradient in pre-strain (0.6% increase over [~]50m) is observed. The increased fibrillar pre-strain is linked to prior research reporting large tissue-level residual strains under compression. The findings may have biomechanical adaptative significance: higher in-built molecular level resilience/damage resistance to physiological compression, and disruption of the molecular-level pre-strains during remodelling of the BCI may be potential factors in osteoarthritis-based degeneration.

bioengineering↗