Naiara Rodriguez-Florez

Insight into differences in nanoindentation properties of bone.

Nanoindentation provides the ideal framework to determine mechanical properties of bone at the tissue scale without being affected by the size, shape, and porosity of the bone. However, the values of tissue level mechanical properties vary significantly between studies. Since the differences in the bone sample, hydration state, and test parameters complicate direct comparisons across the various studies, these discrepancies in values cannot be compared directly. The objective of the current study is to evaluate and compare mechanical properties of the same bones using a broad range of testing parameters. Wild type C56BL6 mice tibiae were embedded following different processes and tested in dry and rehydrated conditions. Spherical and Berkovich indenter probes were used, and data analysis was considered within the elasto-plastic (Oliver-Pharr), viscoelastic and visco-elastic-plastic frameworks. The mean values of plane strain modulus varied significantly depending on the hydration state, probe geometry and analysis method. Indentations in dry bone analyzed using a visco-elastic-plastic approach gave values of 34 GPa. After rehydrating the same bones and indenting them with a spherical tip and utilizing a viscoelastic analysis, the mean modulus value was 4 GPa, nearly an order of magnitude smaller. Results suggest that the hydration state, probe geometry and the limitations and assumptions of each analysis method influence significantly the measured mechanical properties. This is the first time that such a systematic study has been carried out and it has been concluded that the discrepancies in the mechanical properties of bone measured by nanoindentation found in the literature should not be attributed only to the differences between the bones themselves, but also to the testing and analysis protocols.

An Investigation of the Mineral in Ductile and Brittle Cortical Mouse Bone

Bone is a strong and tough material composed of apatite mineral, organic matter, and water. Changes in composition and organization of these building blocks affect bones mechanical integrity. Skeletal disorders often affect bones mineral phase, either by variations in the collagen or directly altering mineralization. The aim of the current study was to explore the differences in the mineral of brittle and ductile cortical bone at the mineral (nm) and tissue (µm) levels using two mouse phenotypes. Osteogenesis imperfecta model, oim‐/‐, mice have a defect in the collagen, which leads to brittle bone; PHOSPHO1 mutants, Phospho1‐/‐, have ductile bone resulting from altered mineralization. Oim‐/‐ and Phospho1‐/‐ were compared with their respective wild‐type controls. Femora were defatted and ground to powder to measure average mineral crystal size using X‐ray diffraction (XRD) and to monitor the bulk mineral to matrix ratio via thermogravimetric analysis (TGA). XRD scans were run after TGA for phase identification to assess the fractions of hydroxyapatite and β‐tricalcium phosphate. Tibiae were embedded to measure elastic properties with nanoindentation and the extent of mineralization with backscattered electron microscopy (BSE SEM). Results revealed that although both pathology models had extremely different whole‐bone mechanics, they both had smaller apatite crystals, lower bulk mineral to matrix ratio, and showed more thermal conversion to β‐tricalcium phosphate than their wild types, indicating deviations from stoichiometric hydroxyapatite in the original mineral. In contrast, the degree of mineralization of bone matrix was different for each strain: brittle oim‐/‐ were hypermineralized, whereas ductile Phospho1‐/‐ were hypomineralized. Despite differences in the mineralization, nanoscale alterations in the mineral were associated with reduced tissue elastic moduli in both pathologies. Results indicated that alterations from normal crystal size, composition, and structure are correlated with reduced mechanical integrity of bone.

Three-Dimensional Handheld Scanning to Quantify Head-Shape Changes in Spring-Assisted Surgery for Sagittal Craniosynostosis.

AbstractThree-dimensional (3D) imaging is an important tool for diagnostics, surgical planning, and evaluation of surgical outcomes in craniofacial procedures. Gold standard for acquiring 3D imaging is computed tomography that entails ionizing radiations and, in young children, a general anaesthesia. Three-dimensional photographic imaging is an alternative method to assess patients who have undergone calvarial reconstructive surgery. The aim of this study was to assess the utility of 3D handheld scanning photography in a cohort of patients who underwent spring-assisted correction surgery for scaphocephaly. Pre- and postoperative 3D scans acquired in theater and at the 3-week follow-up in clinic were postprocessed for 9 patients. Cephalic index (CI), head circumference, volume, sagittal length, and coronal width over the head at pre-op, post-op, and follow-up were measured from the 3D scans. Cephalic index from 3D scans was compared with measurements from planar x-rays. Statistical shape modeling (SSM) was used to calculate the 3D mean anatomical head shape of the 9 patients at the pre-op, post-op, and follow-up. No significant differences were observed in the CI between 3D and x-ray. Cephalic index, volume, and coronal width increased significantly over time. Mean shapes from SSM visualized the overall and regional 3D changes due to the expansion of the springs in situ. Three-dimensional handheld scanning followed by SSM proved to be an efficacious and practical method to evaluate 3D shape outcomes after spring-assisted cranioplasty in individual patients and the population.

Age-related changes in mouse bone permeability.

The determination of lacunar-canalicular permeability is essential for understanding local fluid flow in bone, which may indicate how bone senses changes in the mechanical environment to regulate mechano-adaptation. The estimates of lacunar-canalicular permeability found in the literature vary by up to eight orders of magnitude, and age-related permeability changes have not been measured in non-osteonal mouse bone. The objective of this study is to use a poroelastic approach based on nanoindentation data to characterize lacunar-canalicular permeability in murine bone as a function of age. Nine wild type C57BL/6 mice of different ages (2, 7 and 12 months) were used. Three tibiae from each age group were embedded in epoxy resin, cut in half and indented in the longitudinal direction in the mid-cortex using two spherical fluid indenter tips (R=238 μm and 500 μm). Results suggest that the lacunar-canalicular intrinsic permeability of mouse bone decreases from 2 to 7 months, with no significant changes from 7 to 12 months. The large indenter tip imposed larger contact sizes and sampled larger ranges of permeabilities, particularly for the old bone. This age-related difference in the distribution was not seen for indents with the smaller radius tip. We conclude that the small tip effectively measured lacunar-canalicular permeability, while larger tip indents were influenced by vascular permeability. Exploring the age-related changes in permeability of bone measured by nanoindentation will lead to a better understanding of the role of fluid flow in mechano-transduction. This understanding may help indicate alterations in bone adaptation and remodeling.

Spring-assisted Cranioplasty for the Correction of Nonsyndromic Scaphocephaly: A Quantitative Analysis of 100 Consecutive Cases

Background: Spring-assisted cranioplasty has been proposed as an alternative to total calvarial remodeling for sagittal craniosynostosis. Advantages include its minimally invasive nature, and reduced morbidity and hospital stay. Potential drawbacks include the need for a second procedure for removal and the lack of published long-term follow-up. The authors present a single-institution experience of 100 consecutive cases using a novel spring design. Methods: All patients treated at the authors’ institution between April of 2010 and September of 2014 were evaluated retrospectively. Patients with isolated nonsyndromic sagittal craniosynostosis were included. Data were collected for operative time, anesthetic time, hospital stay, transfusion requirement, and complications in addition to cephalic index preoperatively and at 1 day, 3 weeks, and 6 months postoperatively. Results: One hundred patients were included. Mean cephalic index was 68 preoperatively, 71 at day 1, and 72 at 3 weeks and 6 months postoperatively. Nine patients required transfusion. Two patients developed a cerebrospinal fluid leak requiring intervention. One patient required early removal of springs because of infection. One patient had a wound dehiscence over the spring and one patient sustained a venous infarct with hemiplegia. Five patients required further calvarial remodeling surgery. Conclusions: The authors’ modified spring design and protocol represents an effective strategy in the management of single-suture sagittal craniosynostosis with reduced total operative time and blood loss compared with alternative treatment strategies. In patients referred within the first 6 months of birth, this technique has become the authors’ procedure of choice. In a minority of cases, especially in the older age groups, further remodeling surgery is required. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

A novel soft tissue prediction methodology for orthognathic surgery based on probabilistic finite element modelling

Repositioning of the maxilla in orthognathic surgery is carried out for functional and aesthetic purposes. Pre-surgical planning tools can predict 3D facial appearance by computing the response of the soft tissue to the changes to the underlying skeleton. The clinical use of commercial prediction software remains controversial, likely due to the deterministic nature of these computational predictions. A novel probabilistic finite element model (FEM) for the prediction of postoperative facial soft tissues is proposed in this paper. A probabilistic FEM was developed and validated on a cohort of eight patients who underwent maxillary repositioning and had pre- and postoperative cone beam computed tomography (CBCT) scans taken. Firstly, a variables correlation assessed various modelling parameters. Secondly, a design of experiments (DOE) provided a range of potential outcomes based on uniformly distributed input parameters, followed by an optimisation. Lastly, the second DOE iteration provided optimised predictions with a probability range. A range of 3D predictions was obtained using the probabilistic FEM and validated using reconstructed soft tissue surfaces from the postoperative CBCT data. The predictions in the nose and upper lip areas accurately include the true postoperative position, whereas the prediction under-estimates the position of the cheeks and lower lip. A probabilistic FEM has been developed and validated for the prediction of the facial appearance following orthognathic surgery. This method shows how inaccuracies in the modelling and uncertainties in executing surgical planning influence the soft tissue prediction and it provides a range of predictions including a minimum and maximum, which may be helpful for patients in understanding the impact of surgery on the face.

Spring assisted cranioplasty: A patient specific computational model

Implantation of spring-like distractors in the treatment of sagittal craniosynostosis is a novel technique that has proven functionally and aesthetically effective in correcting skull deformities; however, final shape outcomes remain moderately unpredictable due to an incomplete understanding of the skull-distractor interaction. The aim of this study was to create a patient specific computational model of spring assisted cranioplasty (SAC) that can help predict the individual overall final head shape. Pre-operative computed tomography images of a SAC patient were processed to extract a 3D model of the infant skull anatomy and simulate spring implantation. The distractors were modeled based on mechanical experimental data. Viscoelastic bone properties from the literature were tuned using the specific patient procedural information recorded during surgery and from x-ray measurements at follow-up. The model accurately captured spring expansion on-table (within 9% of the measured values), as well as at first and second follow-ups (within 8% of the measured values). Comparison between immediate post-operative 3D head scanning and numerical results for this patient proved that the model could successfully predict the final overall head shape. This preliminary work showed the potential application of computational modeling to study SAC, to support pre-operative planning and guide novel distractor design.

Statistical shape modelling to aid surgical planning: associations between surgical parameters and head shapes following spring-assisted cranioplasty

PurposeSpring-assisted cranioplasty is performed to correct the long and narrow head shape of children with sagittal synostosis. Such corrective surgery involves osteotomies and the placement of spring-like distractors, which gradually expand to widen the skull until removal about 4 months later. Due to its dynamic nature, associations between surgical parameters and post-operative 3D head shape features are difficult to comprehend. The current study aimed at applying population-based statistical shape modelling to gain insight into how the choice of surgical parameters such as craniotomy size and spring positioning affects post-surgical head shape.MethodsTwenty consecutive patients with sagittal synostosis who underwent spring-assisted cranioplasty at Great Ormond Street Hospital for Children (London, UK) were prospectively recruited. Using a nonparametric statistical modelling technique based on mathematical currents, a 3D head shape template was computed from surface head scans of sagittal patients after spring removal. Partial least squares (PLS) regression was employed to quantify and visualise trends of localised head shape changes associated with the surgical parameters recorded during spring insertion: anterior–posterior and lateral craniotomy dimensions, anterior spring position and distance between anterior and posterior springs.ResultsBivariate correlations between surgical parameters and corresponding PLS shape vectors demonstrated that anterior–posterior (Pearson’s

The use of XFEM to assess the influence of intra-cortical porosity on crack propagation.

r=0.64, p=0.002