During bone regeneration, the periosteum acts as a carrier for key regenerative cues, delivering osteochondroprogenitor cells and crucial growth factors to the injured bone. We developed a biocompatible, 3D polycaprolactone (PCL) melt electro-written membrane to act as a mimetic periosteum. Poly (ethyl acrylate) coating of the PCL membrane allowed functionalization, mediated by fibronectin and low dose recombinant human BMP-2 (rhBMP-2) (10-25 mu g/ml), resulting in efficient, sustained osteoinduction in vitro. In vivo, rhBMP-2 functionalized mimetic periosteum demonstrated regenerative potential in the treatment of rat critical-size femoral defects with highly efficient healing and functional recovery (80%-93%). Mimetic periosteum has also proven to be efficient for cell delivery, as observed through the migration of transplanted periosteum-derived mesenchymal cells to the bone defect and their survival. Ultimately, mimetic periosteum demonstrated its ability to deliver key stem cells and morphogens to an injured site, exposing a therapeutic and translational potential in vivo when combined with unprecedentedly low rhBMP-2 doses.

Mechanical environment plays a crucial role in regulating bone regeneration in bone defects. Assessing the mechanobiological behavior of patient-specific orthopedic scaffolds in-silico could help guide optimal scaffold designs, as well as intra- and post-operative strategies to enhance bone regeneration and improve implant longevity. Additively manufactured porous scaffolds, and specifically triply periodic minimal surfaces (TPMS), have shown promising structural properties to act as bone substitutes, yet their ability to induce mechanobiologially-driven bone regeneration has not been elucidated. The aim of this study is to i) explore the bone regeneration potential of TPMS scaffolds made of different stiffness biocompatible materials, to ii) analyze the influence of pre-seeding the scaffolds and increasing the post-operative resting period, and to iii) assess the influence of patient-specific parameters, such as age and mechanosensitivity, on outcomes. To perform this study, an in silico model of a goat tibia is used. The bone ingrowth within the scaffold pores was simulated with a mechano-driven model of bone regeneration. Results showed that the scaffold's architectural properties affect cellular diffusion and strain distribution, resulting in variations in the regenerated bone volume and distribution. The softer material improved the bone ingrowth. An initial resting period improved the bone ingrowth but not enough to reach the scaffold's core. However, this was achieved with the implantation of a pre-seeded scaffold. Physiological parameters like age and health of the patient also influence the bone regeneration outcome, though to a lesser extent than the scaffold design. This analysis demonstrates the importance of the scaffold's geometry and its material, and highlights the potential of using mechanobiological patient-specific models in the design process for bone substitutes.

A hybrid approach combining the laser powder bed fusion (LPBF) process and post-processing operations through 5-axis milling was employed to manufacture a Ti6Al4V aerospace component. From the design step, the requirements and needs in all the stages of the Hybrid Additive Manufacturing process were taken into account. A numerical simulation of distortions promoted by residual stresses during the additive process was employed to consider material allowance. The status of the as-built and post-processed component was analysed through scanning and CMM inspection and roughness measurements. The 3D scanned model of the as-built LPBF-ed component was used to understand the distortion behaviour of the component and compared to the numerical simulation. Finally, 5-axis milling operations were conducted in some critical surfaces in order to improve surface quality and dimensional accuracy of the as-built com-ponent. The inspection of the as-built and post-processed component showed the improvement achieved through the proposed hybrid approach. The work aims to provide the baselines needed to enable the metal Hybrid Additive Manufacturing of components with complex geometries where mandatory precision is required by integrating high accuracy machining operations as post-processing technique.(c) 2022 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/).

Objective To investigate the relationship between perception of craniofacial deformity, geometric head features, and 3D head shape analyzed by statistical shape modeling (SSM). Patients A total of 18 unoperated patients with scaphocephaly (age = 5.2 +/- 1.1m)-6 were followed-up after spring-assisted cranioplasty (SAC) (age = 9.6 +/- 1.5m)-and 6 controls (age = 6.7 +/- 2.5m). Main Outcome Measures 3D head shapes were retrieved from 3D scans or computed tomography (CTs). Various geometrical features were measured: anterior and posterior prominence, take-off angle, average anterior and posterior lateral and horizontal curvatures, cranial index (CI) (cranial width over length), and turricephaly index (TI) (cranial height over length). SSM and principal component analysis (PCA) described shape variability. All models were 3D printed; the perception of deformity was blindly scored by 9 surgeons and 1 radiologist in terms of frontal bossing (FB), occipital bulleting (OB), biparietal narrowing (BN), low posterior vertex (LPV), and overall head shape (OHS). Results A moderate correlation was found between FB and anterior prominence (r = 0.56, P < .01) and take-off angle (r = - 0.57, P < .01). OB correlated with average posterior lateral curvature (r = 0.43, P < 0.01) similarly to BPN (r = 0.55, P < .01) and LPV (r = 0.43, P < .01). OHS showed strong correlation with CI (r = - 0.68, P < .01) and TI (r = 0.63, P< .01). SSM Mode 1 correlated with OHS (r = 0.66, p < .01) while Mode 3 correlated with FB (r = - 0.58, P < .01). Conclusions Esthetic cranial appearance in craniofacial patients is correlated to specific geometric parameters and could be estimated using automated methods such as SSM.

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.