Additively manufactured lattice structures enable the design of tissue scaffolds with tailored mechanical properties, which can be implemented in porous biomaterials. The adaptation of bone to physiological loads results in anisotropic bone tissue properties which are optimized for site-specific loads; therefore, some bone sites are stiffer and stronger along the principal load direction compared to other orientations. In this work, a semi-analytical model was developed for the design of transversely isotropic lattice structures that can mimic the anisotropy characteristics of different types of bone tissue. Several design possibilities were explored, and a particular unit cell, which was best suited for additive manufacturing was further analyzed. The design of the unit cell was parameterized and in-silico analysis was performed via Finite Element Analysis. The structures were manufactured additively in metal and tested under compressive loads in different orientations. Finite element analysis showed good correlation with the semi-analytical model, especially for elastic constants with low relative densities. The anisotropy measured experimentally showed a variable accuracy, highlighting the deviations from designs to additively manufactured parts. Overall, the proposed model enables to exploit the anisotropy of lattice structures to design lighter scaffolds with higher porosity and increased permeability by aligning the scaffold with the principal direction of the load.

Limited information is available on the effect of sagittal craniosynostosis (CS) on morphological and material properties of the parietal bone. Understanding these properties would not only provide an insight into bone response to surgical procedures but also improve the accuracy of computational models simulating these surgeries. The aim of the present study was to characterise the mechanical and microstructural properties of the cortical table and diploe in parietal bone of patients affected by sagittal CS. Twelve samples were collected from pediatric patients (11 males, and 1 female; age 5.2 +/- 1.3 months) surgically treated for sagittal CS. Samples were imaged using micro-computed tomography (micro-CT); and mechanical properties were extracted by means of micro-CT based finite element modelling (micro-FE) of three-point bending test, calibrated using sample-specific experimental data. Reference point indentation (RPI) was used to validate the micro-FE output. Bone samples were classified based on their macrostructure as unilaminar or trilaminar (sandwich) structure. The elastic moduli obtained using RPI and micro-FE approaches for cortical tables (E-RPI 3973.33 +/- 268.45 MPa and Emicro-FE 3438.11 +/- 387.38 MPa) in the sandwich structure and diploe (E(RPI)1958.17 +/- 563.79 MPa and Emicro-FE 1960.66 +/- 492.44 MPa) in unilaminar samples were in strong agreement (r = 0.86, p < .01). We found that the elastic modulus of cortical tables and diploe were correlated with bone mineral density. Changes in the microstructure and mechanical properties of bone specimens were found to be irrespective of patients' age. Although younger patients are reported to benefit more from surgical intervention as skull is more malleable, understanding the material properties is critical to better predict the surgical outcome in patients <1 year old since age-related changes were minimal.

The aim of this study is, firstly, to create a population-based 3D head shape model for the 0 to 2-year-old subjects to describe head shape variability within a normal population and, secondly, to test a combined normal and sagittal craniosynostosis (SAG) population model, able to provide surgical outcome assessment. 3D head shapes of patients affected by non-cranial related pathologies and of SAG patients (pre- and post-op) were extracted either from head CTs or 3D stereophotography scans, and processed. Statistical shape modelling (SSM) was used to describe shape variability using two models - a normal population model (MODEL1) and a combined normal and SAG population model (MODEL2). Head shape variability was described via principal components analysis (PCA) which calculates shape modes describing specific shape features. MODEL1 (n - 65) mode 1 showed statistical correlation (p < 0.001) with width (125.8 +/- 13.6 mm), length (151.3 +/- 17.4 mm) and height (112.5 +/- 11.1 mm) whilst mode 2 showed correlation with cranial index ( 83.5 mm +/- 6.3 mm, p < 0.001). The remaining 9 modes showed more subtle head shape variability. MODEL2 (n = 159) revealed that post-operative head shape still did not achieve full shape normalization with either spring cranioplasty or total calvarial remodelling. This study proves that SSM has the potential to describe detailed anatomical variations in a paediatric population. (C) 2021 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Sagittal craniosynostosis consists of premature fusion (ossification) of the sagittal suture during infancy, resulting in head deformity and brain growth restriction. Spring-assisted cranioplasty (SAC) entails skull incisions to free the fused suture and insertion of two springs (metallic distractors) to promote cranial reshaping. Although safe and effective, SAC outcomes remain uncertain. We aimed hereby to obtain and validate a skull material model for SAC outcome prediction. Computed tomography data relative to 18 patients were processed to simulate surgical cuts and spring location. A rescaling model for age matching was created using retrospective data and validated. Design of experiments was used to assess the effect of different material property parameters on the model output. Subsequent material optimization¿using retrospective clinical spring measurements¿was performed for nine patients. A population-derived material model was obtained and applied to the whole population. Results showed that bone Young¿s modulus and relaxation modulus had the largest effect on the model predictions: the use of the population-derived material model had a negligible effect on improving the prediction of on-table opening while significantly improved the prediction of spring kinematics at follow-up. The model was validated using on-table 3D scans for nine patients: the predicted head shape approximated within 2 mm the 3D scan model in 80% of the surface points, in 8 out of 9 patients.

Spring-assisted cranioplasty (SAC) is a minimally invasive technique for treating sagittal synostosis in young infants. Yet, follow-up data on cranial growth in patients who have undergone SAC are lacking. This project aimed to understand how the cranial shape develops during the postoperative period, from spring insertion to removal. 3D head scans of 30 consecutive infants undergoing SAC for sagittal synostosis were acquired using a handheld scanner pre-operatively, immediately postoperatively, at follow-up and at spring removal; 3D scans of 41 age-matched control subjects were also acquired. Measurements of head length, width, height, circumference, and volume were taken for all subjects; cephalic index (CI) was calculated. Statistical shape modeling was used to compute 3D average head models of sagittal patients at the different time points. SAC was performed at a mean age of 5.2 months (range 3.3-8.0) and springs were removed 4.3 months later. CI increased significantly (P < 0.001) from pre-op (69.5% +/- 2.8%) to spring removal (74.4% +/- 3.9%), mainly due to the widening of head width, which became as wide as for age-matched controls; however, the CI of controls was not reached (82.3% +/- 6.8%). The springs did not constrain volume changes and allowed for natural growth. Population mean shapes showed that the bony prominences seen at the sites of spring engagement settle over time, and that springs affect the overall 3D head shape of the skull. In conclusion, results reaffirmed the effectiveness of SAC as a treatment method for nonsyndromic single suture sagittal synostosis.

While human adipose-derived stem cells (hADSCs) are known to possess osteogenic differentiation potential, the bone tissues formed are generally considered rudimentary and immature compared with those made by bone-derived precursor cells such as human bone marrow-derived mesenchymal stem cells (hBMSCs) and less commonly studied human calvarium osteoprogenitor cells (hOPs). Traditional differentiation protocols have tended to focus on osteoinduction of hADSCs through the addition of osteogenic differentiation media or use of stimulatory bioactive scaffolds which have not resulted in mature bone formation. Here, we tested the hypothesis that by reproducing the physical as well as biochemical bone microenvironment through the use of three-dimensional (3D) culture and vascularization we could enhance osteogenic maturation in hADSCs. In addition to biomolecular characterization, we performed structural analysis through extracellular collagen alignment and mineral density in our bone tissue engineered samples to evaluate osteogenic maturation. We further compared bone formed by hADSCs, hBMSCs, and hOPs against mature human pediatric calvarial bone, yet not extensively investigated. Although bone generated by all three cell types was still less mature than native pediatric bone, a fibrin-based 3D microenvironment together with vascularization boosted osteogenic maturation of hADSC making it similar to that of bone-derived osteoprogenitors. This demonstrates the important role of vascularization and 3D culture in driving osteogenic maturation of cells easily available but constitutively less committed to this lineage and suggests a crucial avenue for recreating the bone microenvironment for tissue engineering of mature craniofacial bone tissues from pediatric hADSCs, as well as hBMSCs and hOPs.

Purpose Late deformity/indentation is well-recognised following fronto-orbital remodelling (FOR) for metopic synostosis. We hypothesise that if damage to temporalis muscle were a contributor, the thickness of soft tissue and bone in the affected area would be reduced. Materials and methods Soft tissues and bone were separately segmented and reconstructed three-dimensionally from computed tomograms of 8 patients 1.5¿18 years post-FOR performed at 16 ± 2 months for metopic synostosis and from 8 age-matched controls. Soft tissue (taken as proxy for temporalis muscle) and bone thickness overall and in the indented areas were computed. Results Post-FOR, three-dimensional soft tissue thickness maps demonstrated temporalis extending upwards but falling short of the indented area. Overall skull thickness increased with age post-FOR (logarithmic fit R2 = 0.71) and for controls (R2 = 0.90). Although immediately post-FOR the future indented area had a thickness of 98% of control, it decreased linearly to 64% 16 years later (Pearson's r = 0.84). Conclusion These findings suggest that late post-FOR deformity/indentation is enhanced by limited upward extension (or retraction downwards) of temporalis muscle, while bone thickness in the affected area gradually decreases. This supports the hypothesis that aberrant re-attachment of the temporalis muscle makes a material contribution to late deformity following FOR for metopic synostosis.

PURPOSE: Cranial lacunae (foci of attenuated calvarial bone) are CT equivalents of "copper beating" seen on plain skull radiographs in children with craniosynostosis. The qualitative presence of copper beating has not been found to be useful for the diagnosis of intracranial hypertension (IH) in these patients. 3D morphometric analysis (3DMA) allows a more systematic and quantitative assessment of calvarial attenuation. We used 3DMA to examine the relationship between cranial lacunae and IH in children with Crouzon and Apert syndromic craniosynostosis. METHODS: Patients were divided into IH and non-IH groups defined on an intention-to-treat basis. Pre-operative CT scans were converted into 3D skull models and processed to quantify lacunae as a percentage of calvarium surface area (LCP). This was done on individual bone and whole skull basis. RESULTS: Eighteen consecutive children with Crouzon's syndrome and 17 with Apert syndrome were identified. Median age at CT scan was 135 days (range 6-1778). Of the 35 children, 21 required surgery for IH at median age of 364 days (range 38-1710). Of these 21 children, 14 had lacunae with mean LCP of 3% (0-28%). Of the 14 non-IH children, 8 had lacunae with mean LCP of 2% (0-8%). LCP was not significantly different between IH and non-IH groups. Parietal bones were most likely to show lacunae (IH 14/21, non-IH 9/14), followed by occipital (IH 8/21, non-IH 3/14), and frontal (IH 6/21, non-IH 2/14).