Fully customized biomedical implants must respect both aesthetic and functional requirements, which makes both the design and the manufacturing steps not trivial. Therefore, a solid methodology cannot only be focused on the manufacturing process: the final geometry, despite being fully respectful of the patient's morphology, is characterized by heterogeneities that could negatively affect the implant's capability of withstanding a specific loading condition. Therefore, a concurrent approach is necessary by merging manufacturing and structural needs in a proper biomechanical scenario: by extensively relying on the numerical simulation, the manufacturing process can be simulated and the results (in terms of post-process properties of the part) imported as boundary conditions for the evaluation of the load-bearing capacity of the implant interacting with biological structures like the bone tissue and muscle actuators. In the present work, the concurrent approach has been applied for the design of an Mg-based sub-orbital osteosynthesis implant produced using a metal forming process (the superplastic forming). The manufacturing step was simulated to obtain the geometry of the implant: the post-forming properties were then imported into a second numerical model for simulating realistic loading conditions that the implant is subjected to during its service. The resulting state of stress and the occurrence of localized plastic deformation, while accounting for the degradation of the material's yield point due to the grain growth, were used as indicators to tailor the manufacturing step and optimize the post-forming properties (mainly the thickness of the undeformed blank): it was found out that only by increasing the initial thickness of the blank and reducing the forming time (to limit the degradation of the material properties) the plastic deformation could be limited in the implant and a plate design compatible with a realistic biomechanical scenario could be thus obtained.

To develop and evaluate an automated workflow for the setup of single-vertebra finite element (FE) simulations from clinical CT data. Specifically, we quantified how automated endplate identification, vertebra-specific coordinate system definition, and load-application-point assignment influence the simulated fracture-load estimates. We analyzed 113 vertebrae from 70 patients that had previously undergone manual FE setup. The automated pipeline identified vertebral endplates, assigned a vertebra-specific coordinate system, and assigned the load application point for axial compression simulations. Automated setups were visually graded as good, acceptable, or bad using predefined criteria. Agreement with manual reference models was evaluated, and the effects of each setup component on fracture-load estimates were quantified separately. Of 113 vertebrae, 53 (47

Fusion surgery involves replacing degenerated intervertebral discs with artificial implants, usually composed of titanium alloys or PEEK, requiring bone grafting to assist tissue growth. This study aims to evaluate numerically 3D-printed porous ceramic implants as a bioactive alternative. Clinical computed tomographies of an adult patient were used to reconstruct the geometry and to assign mechanical properties to L1 and L2 vertebrae, utilizing a patient-specific anisotropic micromechanics-based model. The influence of different microstructural choices on a porous hydroxyapatite-based scaffold was analysed through finite element analysis, simulating standing and flexion. The analyzed scaffolds included: microstructured Face Centered Cubic (FCC) and Kelvin-based devices with uniform porosity (75%), and a Voronoi microstructured scaffold with uniform (75%) and graded porosity (60% external, 90% internal). Homogenized models were considered as a potential strategy to reduce computational costs. The FCC geometry and graded Voronoi proved more mechanically resistant to failure. Homogenized mechanical properties simplified the model, but didn't accurately represent microstructural behaviour and local mechanical failure couldn't be suitably identified. Patient-specific models allowed for a more accurate representation of mechanical stresses, leading to a reduced risk of structural failure. Hydroxyapatite proves to be a promising material for 3D-printed lumbar interbody fusion cages, able to provide primary stability.

The aim of this work is to assess the printing fidelity, explore the mechanical properties and optimize process parameters of FDM-printed PLA/HA composite samples for maxillofacial and oral applications. Pure PLA and PLA/HA composites with 20 % and 35 % HA content by weight were evaluated. The effects of printing temperature and HA loading on printing fidelity and mechanical properties, as well as the FDM printability of screws and patient-specific membranes, were assessed. Square samples with holes and beam samples, designed with geometrical features comparable to fixation plates and guided bone regeneration (GBR) membranes, were FDM-printed and analyzed for dimensional accuracy and mechanical performance. The results show that holes are geometrical features difficult to print with high accuracy and a printing temperature of 200 °C provides better accuracy and mechanical properties compared to 210 °C. Higher HA loading reduces printability fidelity and increases flexural elastic modulus while decreasing maximum flexural strength and strain. Prototypes of patient-specific GBR membranes and fixation screws were successfully printed using PLA/HA 20, demonstrating the feasibility of producing custom medical devices with FDM technology. Roughness analysis on GBR membranes in PLA/HA 20 revealed no significant differences between the external and internal surfaces or between different printing configurations. Moreover, the FDM printing process does not affect the homogeneous distribution of HA particles within the PLA matrix in PLA/HA 20 composite. The results suggest that a printing parameters optimization procedure is fundamental for achieving the best performance of PLA/HA composites in terms of printing fidelity and mechanical properties. PLA/HA 20 shows promise as a biodegradable alternative to non-biodegradable materials such as titanium, which is commonly used for maxillofacial and oral applications.

Accurate patient-specific modeling and finite element analysis are fundamental for achieving reliable results that can support pre-surgical planning, device design and biomechanical evaluation in oral surgery. This study presents a workflow for image-based patient-specific modeling applied to a guided bone regeneration clinical case. The workflow starts with image-based properties modeling, including bone density calibration, clinical image segmentation, and micro-mechanical bone modeling. Then, a custom device was designed, and a material was selected and its material properties were obtained through mechanical characterization. Lastly, a patient-specific finite element model was created with appropriate boundary conditions to evaluate the biomechanical behavior of the device and the bone state at interfaces with the device and screws. The work highlights the importance of bone density calibration and the modeling of anisotropic and nonhomogeneous bone properties in FEM to accurately evaluate the bone state after a guided bone regeneration surgery. This study has established a methodology for creating patient-specific models based on clinical imaging data in the context of oral surgery. This approach facilitates the biomechanical assessment of 3D-printed devices, as well as the interactions at the interfaces between device and bone, and screws and bone.

Drug-coated balloons (DCBs) aim to deliver drug-loaded surface coating upon inflation at specific vascular sites, yet the role of inflation pressure remains to be defined. We implement a new approach combining ex vivo stamping experiments with in silico simulations to study acute coating transfer by commercial DCBs. This methodology comprises 3 essential pillars: (I) DCB resin inflation and slicing into cylindrical segments for subsequent stamping onto porcine-excised tissue, (II) Numerical inflation of a full DCB replica in an idealized porcine vessel to predict in vivo interfacial contact pressures (CPs) and subsequent interfacial-level numerical stamping to calculate appropriate benchtop forces that recreate these in vivo CP values, and (III) ex vivo stamping experiments and optical analysis of the stamped surfaces (DCB segment and arterial tissue), using a standard high-resolution camera to visualize coating. High-performance liquid chromatography (HPLC) was employed as a validated assay for quantifying drug in tissue samples post-stamping. HPLC analysis revealed a significant correlation with image processing, confirming the validity of the optical method as a tool to quantify DCB coating. Image and HPLC analysis revealed a statistically significant twofold rise in coating area and drug content to tissue, respectively, when the average CP roughly doubled (0.16–0.35 atm) and a non-statistically significant increase in coating area and drug content with a further rough doubling of average CP (0.35 to 0.75 atm). Imaging of DCB segments pre- and post-stamping showed transfer of partial coating thickness at low CP, contrasting with complete transfer at high CP at the same site. 3D confocal images of DCB surfaces revealed variable thickness in the transferred coating. This study introduces a comprehensive methodology for evaluating the efficacy of commercial DCB coating transfer to arterial tissue—a crucial precursor to drug elution studies—while minimizing the number of DCBs needed and improving variable control and realism.

Abstract This study focuses on the finite element simulation and micromechanical characterization of bioactive glass-ceramic scaffolds using Computed micro Tomography ( $$\upmu$$ μ CT) imaging. The main purpose of this work is to quantify the effect of sintering temperature on the morphometry and mechanical performance of the scaffolds. In particular, the scaffolds were produced using a novel bioactive glass material (47.5B) through foam replication, applying six different sintering temperatures. Through $$\upmu$$ μ CT imaging, detailed three-dimensional images of the scaffold’s internal structure are obtained, enabling the extraction of important geometric features and how these features change with sintering temperature. A finite element model is then developed based on the $$\upmu$$ μ CT images to simulate the fracture process under uniaxial compression loading. The model incorporates scaffold heterogeneity and material properties—also depending on sintering temperature—to capture the mechanical response, including crack initiation, propagation, and failure. Scaffolds sintered at temperatures equal to or higher than 700 $$^{\circ }$$ ∘ C exhibit two-scale porosity, with micro and macro pores. Finite element analyses revealed that the dual porosity significantly affects fracture mechanisms, as micro-pores attract cracks and weaken strength. Interestingly, scaffolds sintered at high temperatures, the overall strength of which is higher due to greater intrinsic strength, showed lower normalized strength compared to low-temperature scaffolds. By using a combined strategy of finite element simulation and $$\upmu$$ μ CT-based characterization, bioactive glass-ceramic scaffolds can be optimized for bone tissue engineering applications by learning more about their micromechanical characteristics and fracture response.

Although the impact of local fluid dynamics in the biodegradation of magnesium is well known, currently no studies in the literature address the degradation effects of ocular vitreous on bioresorbable devices made of magnesium, which could be developed as drug delivery carriers. The aim of this study was to investigate the flow-induced corrosion mechanism of magnesium in an ophthalmological environment for future applications in ophthalmic drug delivery. To achieve this, experimental and computational methods were combined. Specifically, a CFD model was employed to design experimental conditions that replicate the ocular flow-induced shear stress (FISS) on manufactured magnesium samples. Pure Mg samples were tested in a bioreactor system capable of imposing the ocular CFD calculated values of FISS on the Mg samples’ surface by varying the pump flow rate. Optimal flow rates for a range of different FISS values specific to the ophthalmological fluid dynamics affecting the device were indeed determined before running the experiments. After conducting customized corrosion tests, morphological observations and profilometric maps of the eroded surfaces of Mg samples were obtained using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). These maps were then post-processed for the parametric evaluation of corrosion rates. Pre-existing localized superficial defects did affect the final corrosion pattern. SEM images and CLSM data confirmed a uniform corrosion mechanism, with corrosion rates of 1.9, 2.7, and 3.4 μm/day under different shear stress conditions (0, 0.01, and 0.032 Pa, respectively). More generally, uniform corrosion on pure Mg samples increased with higher FISS values, and at higher shear stress values (FISS = 0.032 Pa), a notable washing-out effect of the corrosion products was observed. The removal of corrosion products at higher shear stresses suggests that the dynamic ocular environment, influenced by saccadic movements, plays a significant role in the corrosion mechanism of pure magnesium. The corrosion rates determined in this study, in conjunction with clinical drug release requirements, are crucial for designing potential drug-release devices for ocular applications.

Triply-Periodic Minimal Surfaces (TPMS) analytical formulation does not provide a direct correlation between the input parameters (analytical) and the mechanical and morphological properties of the structure. In this work, we created a dataset with more than one thousand TPMS scaffolds for the training of Machine Learning (ML) models able to find such correlation. Finite Element Modeling and image analysis have been used to characterize the scaffolds. In particular, we trained three different ML models, exploring both a linear and non-linear approach, to select the features able to predict the input parameters. Furthermore, the features used for the prediction can be selected in three different modes: i) fully automatic, through a greedy algorithm, ii) arbitrarily, by the user and iii) in a combination of the two above methods: i.e. partially automatic and partially through a user-selection. The latter, coupled with the non-linear ML model, exhibits a median error less than 3% and a determination coefficient higher than 0.89 for each of the selected features, and all of them are accessible during the design phase. This approach has been applied to the design of a hydroxyapatite TPMS scaffolds with prescribed properties obtained from a real trabecular-like hydroxyapatite scaffold. The obtained results demonstrate that the ML model can effectively design a TPMS scaffold with prescribed features on the basis of biomechanical, mechanobiology and technological constraints.

Le Fort I osteotomy is an orthognathic surgery used to correct maxillofacial deformities. The maxilla is cut and can be repositioned using patient-specific titanium fixation plates. The aim of the study is to propose a workflow that exploits the numerical modelling of orthognathic case to obtain the optimization of plate design. The 3D model of a le Fort I case was reconstructed from the patient images to create a finite element model with occlusal and muscular forces. A numerical fatigue analysis was carried out using Matake and Fatemi-Socie criteria. The plate design was optimized minimizing the plate thickness to improve biomechanical compatibility and changing the fillet radius and the thickness in critical regions for fatigue life to ensure adequate fatigue strength. The post-optimized plates show a significant increase in the predicted endurance life, reaching the required limit of 150000 chewing cycles. This work confirms the effectiveness of the optimized plate design to ensure mechanical reliability and reduce the risk of complications and discomfort for the patient.

The knowledge of the mechanical properties of glass-ceramic materials used in bone scaffolds is the key to the optimal design of tissue engineering devices. In this paper, the elastic properties and fracture toughness of silicate bioactive glass-ceramics based on the 47.5B parent composition were quantified for the first time through nanoindentation. Specifically, the effect of sintering temperature was investigated by testing samples sintered at six different temperatures. The samples sintered at higher temperatures exhibited elastic modulus and fracture toughness higher than those of the lower temperature samples. Both properties are comparable with those shown by similar bioactive glasses available in literature, supporting the mechanical suitability of the materials for bone applications. An estimation of tensile strength as a function of flaw size is also provided by means of fracture mechanics approaches.

In this work, we present a new experimental setup for the assessment of the anisotropic properties of Bovine Pericardium (BP) membranes. The chemically fixed BP samples have been subjected to a bulge test with in situ confocal laser scanning at increasing applied pressure. The high resolution topography provided by the confocal laser scanning has allowed to obtain a quantitative measure of the bulge displacement; after polynomial fitting, principal curvatures have been obtained and a degree of anisotropy (DA) has been defined as the normalized difference between the maximum and minimum principal curvatures. The experiments performed on the BP membranes have allowed us to obtain pressure-displacement data which clearly exhibit distinct principal curvatures indicating an anisotropic response. A comparison with curvatures data obtained on isotropic Nitrile Buthadiene Rubber (NBR) samples has confirmed the effectiveness of the experimental setup for this specific purpose. Numerical simulations of the bulge tests have been performed with the purpose of identifying a range of constitutive parameters which well describes the obtained range of DA on the BP membranes. The DA values have been partially validated with biaxial tests available in literature and with suitably performed uni-axial tensile tests.

Hydroxyapatite is one of the materials of choice for tissue engineering bone scaffolds manufacturing. Vat photopolymerization (VPP) is a promising Additive Manufacturing (AM) technology capable of producing scaffolds with high resolution micro-architecture and complex shapes. However, mechanical reliability of ceramic scaffolds can be achieved if a high fidelity printing process is obtained and if knowledge of the intrinsic mechanical properties of the constituent material is available. As the hydroxyapatite (HAP) obtained from VPP is subjected to a sintering process, the mechanical properties of the material should be assessed with specific reference to the process parameters (e.g. sintering temperature) and to the specific characteristic size of the microscopic features in the scaffolds. In order to tackle this challenge the HAP solid matrix of the scaffold was mimicked in the form of miniaturized samples suitable for ad hoc mechanical characterization, which is an unprecedented approach. To this purpose small scale HAP samples, having a simple geometry and size similar to that of the scaffolds, were produced through VPP. The samples were subjected to geometric characterization and to mechanical laboratory tests. Confocal laser scanning and Computed micro-Tomography (micro-CT) were used for geometric characterization; while, micro-bending and nanoindentation were used for mechanical testing. Micro-CT analyses have shown a highly dense material with negligible intrinsic micro-porosity. The imaging process allowed quantifying the variation of geometry with respect to the nominal size showing high accuracy of the printing process and identifying printing defects on one specific sample type, depending on the printing direction. The mechanical tests have shown that the VPP produces HAP with an elastic modulus as high as approximately 100GPa and flexural strength of approximately 100MPa. The results of this study have shown that vat photopolymerization is a promising technology capable of producing high quality HAP with reliable geometric fidelity.

Bone scaffolding is a promising approach for the treatment of critical-size bone defects. Hydroxyapatite can be used to produce highly porous scaffolds as it mimics the mineralized part of bone tissue, but its intrinsic brittleness limits its usage. Among 3D printing techniques, vat photopolymerization allows for the best printing resolution for ceramic materials. In this study, we implemented a Computed micro-Tomography based Finite Element Model of a hydroxyapatite porous scaffold fabricated by vat photopolymerization. We used the model in order to predict the elastic and fracture properties of the scaffold. From the stress-strain diagram of a simulated compression test, we computed the stiffness and the strength of the scaffolds. We found that three morphometric features substantially affect the crack pattern. In particular, the crack propagation is not only dependent on the trabecular thickness but also depends on the slenderness and orientation of the trabeculae with respect to the load. The results found in this study can be used for the design of ceramic scaffolds with heterogeneous pore distribution in order to tailor and predict the compressive strength.

The mosquito proboscis is an efficient microelectromechanical system, which allows the insect to feed on vertebrate blood quickly and painlessly. Its efficiency is further enhanced by the insect saliva, although through unclear mechanisms. Here, we describe the initial trigger of an unprecedented feedback signaling pathway in Aedes mosquitoes affecting feeding behavior. We identified LIPS proteins in the saliva of Aedes mosquitoes that promote feeding in the vertebrate skin. LIPS show a new all-helical protein fold constituted by two domains. The N-terminal domain interacts with a cuticular protein (Cp19) located at the tip of the mosquito labrum. Upon interaction, the morphology of the labral cuticle changes, and this modification is most likely sensed by proprioceptive neurons. Our study identifies an additional role of mosquito saliva and underlines that the external cuticle is a possible site of key molecular interactions affecting the insect biology and its vector competence.

In this study, the mechanical properties of two classes of robocast glass scaffolds are obtained through Computed micro-Tomography (micro-CT) based Finite Element Modeling (FEM) with the specific purpose to explicitly account for the geometrical defects introduced during manufacturing. Both classes demonstrate a fiber distribution along two perpendicular directions on parallel layers with a 90∘ tilting between two adjacent layers. The crack pattern identified upon compression loading is consistent with that found in experimental studies available in literature. The finite element models have demonstrated that the effect of imperfections on elastic and strength properties may be substantial, depending on the specific type of defect identified in the scaffolds. In particular, micro-porosity, fiber length interruption and fiber detaching were found as key factors. The micro-pores act as stress concentrators promoting fracture initiation and propagation, while fiber detachment reduces the scaffold properties substantially along the direction perpendicular to the fiber plane.

As the incidence of cardiovascular diseases has been growing in recent years, the need for small-diameter vascular grafts is increasing. Considering the limited success of synthetic grafts, vascular tissue engineering/repair/regeneration aim to find novel solutions. Silk fibroin (SF) has been widely investigated for the development of vascular grafts, due to its good biocompatibility, tailorable biodegradability, excellent mechanical properties, and minimal inflammatory reactions. In this study, a new generation of three-layered SF vascular scaffolds has been produced and optimized. Four designs of the SILKGraft vascular prosthesis have been developed with the aim of improving kink resistance and mechanical strength, without compromising the compliance with native vessels and the proven biocompatibility. A more compact arrangement of the textile layer allowed for the increase in the mechanical properties along the longitudinal and circumferential directions and the improvement of the compliance value, which approached that reported for the saphenous and umbilical veins. The higher braid density slightly affected the grafts’ morphology, increasing surface roughness, but the novel design mimicked the corrugation approach used for synthetic grafts, causing significant improvements in kink resistance.

Abstract In this study, the mechanical properties of glass scaffolds manufactured by robocasting are investigated through micro computed tomography ( $$\mu -CT$$ μ - C T ) based finite element modeling. The scaffolds are obtained by printing fibers along two perpendicular directions on parallel layers with a $$90^\circ $$ 90 ∘ tilting between two adjacent layers. A parametric study is first presented with the purpose to assess the effect of the major design parameters on the elastic and strength properties of the scaffold; the mechanical properties of the 3D printed scaffolds are eventually estimated by using the $$\mu -CT$$ μ - C T data with the aim of assessing the effect of defects on the final geometry which are intrinsic in the manufacturing process. The macroscopic elastic modulus and strength of the scaffold are determined by simulating a uniaxial compressive test along the direction which is perpendicular to the layers of the printed fibers. An iterative approach has been used in order to determine the scaffold strength. A partial validation of the computational model has been obtained through comparison of the computed results with experimental values presented in [10] on a ceramic scaffold having the same geometry. All the results have been presented as non-dimensional values. The finite element analyses have shown which of the selected design parameters have the major effect on the stiffness and strength, being the porosity and fiber shifting between adjacent layers the most important ones. The analyses carried out on the basis of the $$\mu -CT$$ μ - C T data have shown elastic modulus and strength which are consistent with that found on ideal geometry at similar macroscopic porosity. Graphic Abstract In this work, elastic and strength properties of glass-ceramic Bone Tissue Engineering scaffolds manufactured by robocasting are investigated through micro-CT based finite element models. An incremental simulation using a multi-grid finite element solver has been implemented to perform a parametric study on the effect of the major geometrical parameters of the scaffold design as well as the effect. Eventually, the effect of the geometrical imperfections deriving from the 3D printing process has been investigated by means of micro-CT image-based models. The porosity and the shifting between adjacent layers play the dominant role in determing elasticity and strength of the scaffolds. The elastic and strength properties of 3D-printed real scaffold were assessed to be consistent those obtained from the idealized geometric models, at least for the subdomain used in this study.

An advanced metal-ceramic brazing joint HfB2/NiB/HfB2, especially suitable for aerospace and energy applications, was subjected to instrumented nanoindentation at room temperature. A Berkovich pyramidal tip was utilized, with a prescribed maximum load equal to 200 mN, generating measured depths around one micrometer. By repeating the indentation experiments over a regular grid in a neighborhood of the joint, insights were provided into the mechanical properties of different phases and their spatial variability after the joining process, suggesting the possible infiltration of the braze and even the presence of residual stress fields.

Understanding the mechanical behavior and failure mechanisms of stretchable electronics is key in developing reliable and long-lasting devices. In this work a micron-scale stretchable system consisting of an aluminum serpentine patterned interconnect adhered to a polyimide substrate is studied. In-situ experiments are performed where the stretchable sample is elongated, while the surface topography is measured using a confocal microscope. From the resulting height profiles the microscopic three-dimensional deformations are extracted using an adaptive isogeometric digital height correlation algorithm. The displacement information is compared to realistic numerical simulations, in which the interface behavior is described by cohesive zone elements. It is concluded that despite fitting the traction separation law parameters, the model fails to correctly capture the distinct out-of-plane buckling (with magnitude of a few micron) of the interconnect. The model is updated with residual stresses resulting from processing and crystal plasticity induced behavior (decreased yield strength) in the aluminum layer, but both measures are not resulting in the experimentally observed deformations. Finally, mixed-mode cohesive zones are implemented, in which the properties are different in the shear and normal direction. After fitting the corresponding parameters to the experimental data, the model shows realistic in-plane and out-of-plane deformations. Also a predictive simulation for a different geometry results in the correct experimentally measured behavior. It is concluded that the aluminum-polyimide interface mode-angle dependency explains the observed microscopic failure mode of local delamination and buckle formation.