Methods for medical applications
Ambito disciplinare
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Mandibular bone segmentation from CT scans: Quantitative and qualitative comparison among software
Dental Materials, 40(8), pp. e11-e22
3D scanningGeometric modeling and processingImage Processing & Applications
Abstract
Objectives: Nowadays, a wide variety of software for 3D reconstruction from CT scans is available; they differ for costs, capabilities, a priori knowledge, and, it is not trivial to identify the most suitable one for specific purposes. The article is aimed to provide some more information, having set up various metrics for the evaluation of different software's performance. Methods: Metrics include software usability, segmentation quality, geometric accuracy, mesh properties and Dice Similarity Coefficient (DSC). Five different software have been considered (Mimics, D2P, Blue Sky Plan, Relu, and 3D Slicer) and tested on four cases; the mandibular bone was used as a benchmark. Results: Relu software, being based on AI, was able to solve some very intricate geometry and proved to have a very good usability. On the other side, the time required for segmentation was significantly higher than other software (reaching over twice the time required by Mimics). Geometric distances between nodes position calculated by different software usually kept below 2.5 mm, reaching 3.1 mm in some very critical area; 75th percentile q75 is generally less than 0.5 mm, with a maximum of 1.11 mm. Dealing with consistency among software, the maximum DSC value was observed between Mimics and Slicer, D2P and Mimics, and D2P and Slicer, reaching 0.96. Significance: This work has demonstrated how mandible segmentation performance among software was generally very good. Nonetheless, differences in geometric accuracy, usability, costs and times required can be significant so that information here provided can be useful to perform an informed choice.
Keywords: 3D reconstruction , CT scans , DSC , Geometric accuracy , Mandible , Segmentation , Usability
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Sensitivity of radiomics features to region volume: A CT phantom study
2024 International Conference on Control, Automation and Diagnosis, ICCAD 2024
Image Processing & Applications
Abstract
The extraction of quantitative parameters (features) from medical images to build prediction models for computer-assisted clinical decision making (radiomics) has attracted a lot of research attention in recent years. Radiomics features may be influenced by the size of the region of interest (ROI) and it is recommended to employ volume-independent features to reduce the risk of biased prediction models. Despite being a crucial factor, the influence of ROI volume on radiomics features has been largely overlooked in the literature, with only few studies addressing this aspect. In this work we investigated the sensitivity to ROI volume of 103 conventional radiomics features from seven classes under absolute and relative signal resampling. The analysis was carried out on a set of 90 lesion-agnostic ROIs from a CT phantom. We identified a total of 45 and 54 features significantly correlated with volume under absolute and relative signal resampling, respectively. We also determined that signal resampling had an influence on the direction of the relationship, with relative resampling leading to a significant rise in the number of features negatively correlated with volume.
Keywords: Computed Tomography , Precision medicine , Radiomics , Region of interest , Shape , Texture
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A mechano-regulation model to design and optimize the surface microgeometry of titanium textured devices for biomedical applications
Journal of the Mechanical Behavior of Biomedical Materials, 157
Additive manufacturingGeometric modeling and processingVirtual prototyping and digital twin
Abstract
In a technological context where, thanks to the additive manufacturing techniques, even sophisticated geometries as well as surfaces with specific micrometric features can be realized, we propose a mechano-regulation algorithm to determine the optimal microgeometric parameters of the surface of textured titanium devices for biomedical applications. A poroelastic finite element model was developed including a portion of bone, a portion of a textured titanium device and a layer of granulation tissue separating the bone from the device and occupying the space between them. The algorithm, implemented in the Matlab environment, determines the optimal values of the root mean square and the correlation length that the device surface must possess to maximize bone formation in the gap between the bone and the device. For low levels of compression load acting on the bone, the algorithm predicts low values of root mean square and high values of correlation length. Conversely, high levels of load require high values of root mean square and low values of correlation length. The optimal microgeometrical parameters were determined for various thickness values of the granulation tissue layer. Interestingly, the predictions of the proposed computational model are consistent with the experimental results reported in the literature. The proposed algorithm shows promise as a valuable tool for addressing the demands of precision medicine. In this approach, the device or prosthesis is no longer designed solely based on statistical averages but is tailored to each patient's unique anthropometric characteristics, as well as considerations related to their metabolism, sex, age, and more.
Keywords: Additive manufacturing techniques , Correlation length , Mechanobiology , Optimal surface roughness , Root mean square
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Finite Element Modeling of Cells Adhering to a Substrate: An Overview
Applied Sciences (Switzerland), 14(6)
Virtual prototyping and digital twin
Abstract
In tissue formation and regeneration processes, cells often move collectively, maintaining connections through intercellular adhesions. However, the specific roles of cell–substrate and cell-to-cell mechanical interactions in the regulation of collective cell migration are not yet fully understood. Finite element modeling (FEM) may be a way to assess more deeply the biological, mechanical, and chemical phenomena behind cell adhesion. FEM is a powerful tool widely used to simulate phenomena described by systems of partial differential equations. For example, FEM provides information on the stress/strain state of a cell adhering to a substrate, as well as on its mechanobiological behavior. This review paper, after briefly describing basic principles of cell adhesion, surveys the most important studies that have utilized FEM to investigate the structural response of a cell adhering to a substrate and how the forces acting on the cell–substrate adhesive structures affect the global cell mechanical behavior.
Keywords: biotechnology , cell adhesion , finite element modeling , mechanobiology
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Virtual Stigmometer Widget (ViSti) for Precise 5DOF Dental Drill Tool Positioning with Augmented Reality
Lecture Notes in Mechanical Engineering, pp. 479-487
Human factors and ergonomicsVirtual and augmented reality
Abstract
Dental tool positioning is a challenging manual operation that requires precise 5DOF positioning of the drill -rotation around the tool is not influential- minimal error can result in grave consequences such as nerve and bone damage. Augmented Reality (AR) can help to assist tool positioning, but the widgets proposed in the literature are quasi-static, commonly using virtual 3D cylinders or lines to be visually collimated and eventually supported by color change. We draw our inspiration from the photographic viewfinder and propose a novel Virtual Stigmometer Widget (ViSti) to convey tool positioning error magnitude to the dentist. The widget slightly blurs the view and gradually focuses it while approaching the target (i.e., implant drilling position) till it is perfectly collimated. We conducted a within subjects experiment (N = 30) to compare our widget with the golden standard in 32 positioning tasks. NASA-TLX results demonstrated that our widget reduces frustration (−43%), and mental demand (−19%), and the user perceives a better performance (+8%). However, the expected tradeoff is effort (+34%), and physical (+33%) temporal demand (+4%). Our widget demonstrated to have a potential usage for dentistry and in further fields where 5DOF precision is crucial.
Keywords: 5DOF manipulation , Augmented Reality , Dental Implantology , Human Centered Design , Stigmometer
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Effects of Oral Appliances for Obstructive Sleep Apnoea in Reduced Periodontium: A Finite Element Analysis
International Dental Journal
Virtual prototyping and digital twin
Abstract
Background and objective: In the literature, no studies correlate the effects of mandibular advancement devices (MADs) with different titration systems to periodontitis. Through a finite element analysis (FEA), this study investigates the effects generated on periodontal ligaments (PDLs) and teeth by four commercial MADs in periodontal health and with 15% bone resorption. Methods: Four MADs (Somnodent Flexâ„¢, Somnodent Avantâ„¢, Orthoapneaâ„¢, and Herbstâ„¢) were digitalised starting from the impressions of a patient's dental arches. A force of 11.18 N, representing an advancement of 9.5 mm, was applied, and a FEA was subsequently performed. After measuring the stresses and displacements on the PDLs and teeth in healthy periodontal conditions, the vertical dimension of the alveolar bone was reduced by 15%, and measurements were repeated. Results: In terms of PDL stress, Herbstâ„¢ is the device which guarantees a more uniform increment in case of the first stage of periodontitis (+7% for mandibular and maxillary PDLs compared to the healthy condition). For Somnodentâ„¢ devices, the PDLs stress increment is almost null for mandibular PDLs but much higher than Herbstâ„¢ for maxillary PDLs (+17% and +21% for Flexâ„¢ and Avantâ„¢). Orthoapneaâ„¢ determines a PDL stress augmentation between the other devices (+16% and +7%, respectively, for maxillary and mandibular PDLs). Concerning teeth movement, Herbstâ„¢ and Orthoapneaâ„¢ determine a lower and more uniform displacement than Somnodent devices. Conclusions: The stress distribution and teeth displacement are strictly related to MAD geometry. Since its minor effects on teeth and PDLs, the Herbstâ„¢ could be more appropriate in patients with periodontitis.
Keywords: Finite element analysis , Finite element method , Mandibular advancement device , Obstructive sleep apnoea , Periodontal disease , Periodontal stress
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Periodontal effects of two Somnodent oral devices for the treatment of OSA: A finite element study
Cranio - Journal of Craniomandibular and Sleep Practice, 42(4), pp. 400-410
Virtual prototyping and digital twin
Abstract
Objective: The study aims to evaluate the stresses and the deformations generated at the periodontal level by two mandibular advancement devices (MADs) using finite element analysis. Methods: A three-dimensional digital model of the skull of a 29-year-old patient was created using a CBCT. The 3D models of two MADs (Somnodent FlexTM and Somnodent AvantTM) were reconstructed from scanning prototypes based on the patient's anatomy. The overall geometry was imported into software for the finite element study. A force of 11.18 N representing an advancement of 9.5 mm was applied to the devices. A finite element analysis wfas subsequently performed. Results: Somnodent FlexTM generates a peak of 3.27 kPa on periodontal ligaments and 287 kPa on teeth. For Somnodent AvantTM the maximum stress is 4.53 kPa on periodontal ligaments and 467 kPa on teeth. Conclusion: Different activation mechanisms of the devices generate stresses of different entities.
Keywords: finite element analysis , mandibular advancement device , Obstructive sleep apnea , periodontal ligaments
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A Numerical Simulation Approach to Study the Effects of MADs Embedded with Elastic Bands in OSA Treatment
Lecture Notes in Mechanical Engineering, pp. 12-20
Virtual prototyping and digital twin
Abstract
Obstructive Sleep Apnea (OSA) is a nocturnal respiratory disorder characterised by recurrent episodes of partial or total obstruction of the upper airways due to the collapse of the pharyngeal tissue. Mandibular Advancement Devices (MADs) restore regular breathing during sleep by advancing the lower jaw in a controlled way to increase the upper airway volume. However, the relaxation of muscle tone that naturally occurs during sleep induces a vertical mouth opening that impairs the efficacy of the treatment. Thus, elastic bands are recommended to keep the mouth firmly closed. Despite successfully treating OSA, inadequate evidence exists about the effects of MADs supported by elastic bands on teeth and Periodontal Ligaments (PDLs). This study aims to develop a numerical simulation approach through the finite element method to evaluate the behaviour and the effects (displacement and stress fields) of MADs embedded with intermaxillary elastics on PDLs and teeth of patients suffering from OSA. Findings confirm the efficacy of elastics in controlling the mouth opening and reveal a stress increase at the anchorage regions. Thus, their use should be advised to patients who do not suffer from periodontal problems in the anterior region of the mouth.
Keywords: Biomechanics , Finite Element Method , Obstructive Sleep Apnea , Oral Appliance , Teeth Displacement
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Mixed Reality and Maxillofacial Surgery: An Interactive Twofold-Modality Application
Lecture Notes in Mechanical Engineering, pp. 504-511
Human factors and ergonomicsVirtual and augmented reality
Abstract
Using custom-made physical cutting guides in maxillofacial surgery presents several drawbacks, mainly related to design, time, and costs. Even if the literature provides several Augmented Reality (AR) solutions, they mostly display cutting planes and static assistance for repositioning. This work proposes a Mixed Reality (MR) application, deployed on Microsoft HoloLens2, to guide the surgeon in maxillofacial osteotomies and repositioning through intuitive and interactive digital content. A holographic panel allows selecting between the osteotomy and repositioning modes. With the first one, the cutting lines and the drilling points for the fixation plates are overlaid on the patient's skull. With the second one, three different kinds of feedback simultaneously guide the surgeon toward the correct final bone placement, step-by-step, according to the real-time fragment displacement. The MR app was tested by seven inexperienced subjects using a 3D-printed skull. Satisfactory results were obtained for maxillary osteotomy (i.e., less than 1.5 mm deviations) and relocation (i.e., the accuracy is about 0.7 mm and 0.6°).
Keywords: Augmented Reality , Healthcare Design , HoloLens 2 , Maxillofacial Surgery , Mixed Reality
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Distinguishing Kidney Tumor Types Using Radiomics Features and Deep Features
IEEE Access, 12, pp. 84241-84252
Image Processing & Applications
Abstract
Despite technological advances in diagnostic imaging, to distinguish the type of renal tumor without performing a biopsy is still an unsolved challenge. In particular, this is even more striking in the case of clear cell renal cell carcinoma and small oncocytomas. To tackle this problem, a fully automated tool is proposed that can provide decision support for physicians to distinguish between these two types of masses in the most critical cases. In this work three approaches for the development of this tool are implemented and compared, specifically two approaches are based on the use of radiomic features and one on the use of deep features. The nnU-net is exploited to achieve tumor segmentation necessary to obtain the different types of features. The architectures are trained and tested by combining two different datasets, the public dataset KiTS2019 and data from the Careggi University Hospital. The best method is able to obtain 73.77% balanced accuracy, 94.59% sensitivity, 52.94% specificity and 86.84% accuracy.
Keywords: Cancer classification , clear cell renal cell carcinoma , computer aided diagnosis , deep learning , oncocytoma , radiomics
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A Real-Time Acquisition Method Development for the Wrist Movements Rehabilitation
Lecture Notes in Mechanical Engineering, pp. 21-29
3D scanningAdditive manufacturing
Abstract
Current technological developments in the field of sensor capture and additive manufacturing (AM) from computer models have led to innovative solutions for a 3D reconstruction of anatomical parts of the human body in real time, enabling interesting applications in the medical field and especially in orthopedics. The following work proposes the use of new technologies applied to tele-rehabilitation so that the patient can benefit from remote rehabilitation services. The wrist motion performed by the physical therapist was to be compared with the wrist motion of the patient undergoing rehabilitation, so as to obtain a proper analysis on the treatment to be followed, the expected timing and the recovery goals. Future applications could involve the use of the proposed system within hospitals and rehabilitation centers in order to support health care providers, improve patient care and quality of life, and contribute to the innovation of new approaches for medical assessment.
Keywords: Acquisition , Flexion-Extension , Radial-Ulnar deviation , Rehabilitation , Wrist
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A novel procedure for medial axis reconstruction of vessels from Medical Imaging segmentation
Heliyon, 10(11)
Image Processing & Applications
Abstract
A procedure for reconstructing the central axis from diagnostic image processing is presented here, capable of solving the widespread problem of stepped shape effect that characterizes the most common algorithmic tools for processing the central axis for diagnostic imaging applications through the development of an algorithm correcting the spatial coordinates of each point belonging to the axis from the use of a common discrete image skeleton algorithm. The procedure is applied to the central axis traversing the vascular branch of the cerebral system, appropriately reconstructed from the processing of diagnostic images, using investigations of the local intensity values identified in adjacent voxels. The percentage intensity of the degree of adherence to a specific anatomical tissue acts as an attraction pole in the identification of the spatial center on which to place each point of the skeleton crossing the investigated anatomical structure. The results were shown in terms of the number of vessels identified overall compared to the original reference model. The procedure demonstrates high accuracy margin in the correction of the local coordinates of the central points that permits to allocate precise dimensional measurement of the anatomy under examination. The reconstruction of a central axis effectively centered in the region under examination represents a fundamental starting point in deducing, with a high margin of accuracy, key informations of a geometric and dimensional nature that favours the recognition of phenomena of shape alterations ascribable to the presence of clinical pathologies.
Keywords: Medial axis , Medical Imaging , Morphological analysis , Vessel reconstruction
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Cerebral Vessels Diagnostic Investigation: Vessel Classification from Medial Axis Evaluation
Lecture Notes in Mechanical Engineering, pp. 48-56
Image Processing & Applications
Abstract
The present research work intends to examine the anatomical distribution of cerebral vessels, starting from the automatic processing of diagnostic image acquisition sequences, with the aim of identifying the characteristic parameters of their structural conformation, such as terminal points and bifurcations, and statistic connotations closely associated with the formation of pathological phenomena. To do this, a local connectivity investigation was used which, starting from the reconstruction of the central axis crossing the vessels, elaborates a process of sequential ordering of each section with the aim of investigating the spatial conformation of the vessels structure, identifying branches and regions of origin. The proposed algorithm also elaborates a punctual analysis of the vascular branches, giving rise to a three-dimensional reconstruction of the morphological and topological characterization of the vessels in support of the clinical examination. The aim is to provide a fast and accurate procedure capable of automatically interpreting diagnostic analyses of brain vessels to support clinical investigation.
Keywords: 3D Reconstruction , Cerebral Vessels , Medial Axis , Medical Imaging , Minimum Spanning Tree
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Diagnostic Enface Imaging of Retinal Vascularization: Topological Reconstruction and Intersection Identification
Lecture Notes in Mechanical Engineering, pp. 38-47
Image Processing & Applications
Abstract
The work here presented elaborates an analysis of the retinal images, with the aim of characterizing their morphological conformation through the recognition of remarkable parameters such as, among all, the number of vessels, terminal points and bifurcation. The correct identification of each single vessel belonging to the vascular distribution represents a point that has not yet been fully consolidated by the scientific community. The reason lies in the fact that the interpretation of enface images, in which the distribution of the vases is imprinted on a two-dimensional plane, makes it difficult to discern each single section of the vase by following its entire spatial development, due to the multiple overlaps with different pot portions. The aim of this research work is to ensure that the limits encountered in modern retinal image processing algorithms are overcome, through the use of an evaluative comparison of contiguous vessel portions on the basis of local dimensional and intensity similarity criteria. In this way, it is possible to trace the correct attribution of the spatial placement of each vessel, taking it into account in the relative classification in the entire vascular branch of clinical interest.
Keywords: Medical Imaging , Retina Fundus , Vessels Connectivity , Vessels Intersections
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Improvement of the LPG-D probe with sensors and electronics for the objective assessment of burn scars in pediatric cases
2024 IEEE International Workshop on Metrology for Industry 4.0 and IoT, MetroInd4.0 and IoT 2024 - Proceedings, pp. 482-487
Abstract
Objective assessment of burn scars is critical for monitoring treatment efficacy and improving the quality of regenerated skin, particularly in pediatric cases where scar management is critical for long-term healing. In this context, this study presents an improvement with the introduction of sensors in the LPG-D (Louis Paul Guitay Device) probe, which was developed in the T3Ddy laboratory with the primary goal of objectively assessing burn scar pliability. The central component of the new prototipe is the incorporation of a magnetic encoder-based position detection system, which improves the accuracy and reliability of the pliability assessment. Through rigorous testing, including evaluation of maximum acquisition rate, repeatability of sensor measurements, and suction effect, the study demonstrated the device's ability to provide an accurate and reliable objective assessment of scar pliability. This advancement is very promising for improving the management of burn scar treatments in pediatric patients, enabling clinicians to make more informed decisions based on objective data. In addition, the study proposes a new software platform that integrates an angular encoder and a distance sensor, enabling simultaneous data reading and analysis. Taking advantage of the versatility and efficiency of the Python programming language, the software facilitates the interpretation of the device's position on the scar and its pliability, providing clinicians with useful information for treatment optimization.
Keywords: Burn Scar , Distance sensor , LPG treatment , Objective evaluations
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3D printed training simulator for transcatheter edge-to-edge repair of the tricuspid valve: A proof-of-concept
Annals of 3D Printed Medicine, 15
Abstract
Background: Tricuspid regurgitation (TR) treatments have gradually shifted toward a more interventional approach and transcatheter edge-to-edge repair (TEER) has assumed a first-order role. TriClipâ„¢ by Abbott (Menlo Park, USA) is one of the most widely used devices for tricuspid repair. TEER procedures are recognised as technically challenging, characterized by a steep learning curve. For this reason, specialized training is necessary. The aim of this work is to develop and test a novel 3D printed training simulator, which considers both anatomical and mechanical characteristics, specifically designed for this kind of procedure. Methods: Starting from routinely acquired computed tomography (CT) images, a 3D digital model of the heart was reconstructed. This was then properly “augmentedâ€, so that it could realistically reproduce the key features involved in the procedure. The simulator was manufactured exploiting the Polyjet 3D printed. Proper materials selection was performed to accurately reproduce mechanical properties. The manufactured prototype was then tested by a specialized professional, with the TriClipâ„¢ system. Results: The simulator was assessed to practice access, navigation, catheter steering and leaflet grasping. Throughout the process, appropriately placed cameras ensured that the operators could visualize the crucial steps on a screen. Even if a deeper evaluation is needed, preliminary feedback is satisfactory. Conclusions: In this study, a new training simulator for TriClipâ„¢ procedure was designed, produced, and preliminary assessed. Further studies will have to demonstrate the advantages of using this simulator design to shorten the learning curve and subsequently lead to better clinical outcomes.
Keywords: 3D printing , Simulation-based training , Transcatheter edge-to-edge repair , TriClipâ„¢ procedure , Tricuspid regurgitation
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LUNG OPERATION TRAINING IN LOW-COST VIRTUAL REALITY SIMULATION ENVIRONMENTS
Proceedings European Council for Modelling and Simulation Ecms, 38(1), pp. 536-542
Engineering educationVirtual and augmented reality
Abstract
Surgical operations must be preformed by skilled and qualified personnel. Training is therefore of paramount importance to master enough skill to succeeds in the tasks without endangering the health of the patients. Combining different types of training activities, can help reaching the goal in a quicker and more effective way. In this scenario, Virtual Reality represents an interesting step, particularly thanks to the reduction in the cost of the equipment that have made their adoption affordable and their availability widespread. In this work, we present our advances in training lung operations with low-cost virtual reality simulation environments.
Keywords: Simulation , surgical operations , training , Virtual reality
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Towards Parametric Modelling of Human Bronchial Tree for Computational Fluid Dynamics
Lecture Notes in Mechanical Engineering, pp. 196-203
Abstract
This work discusses the development and application of a parametric CAD model of the human bronchial tree, for use in computational fluid dynamics simulations. The model, which represents the trachea, bronchi, and early airway bifurcations, is based on geometrical parameters derived from existing literature. It can be edited by easily varying parameters in an external spreadsheet, offering an efficient alternative to patient-specific models, which often require the use of time-consuming segmentation procedures. The developed model was utilized to run fluid dynamic simulations, including a scenario that represents respiratory system dysfunctions. These are typical of diseases such as acute respiratory distress syndrome, which can be also triggered by recently emerged COVID-19. The results of these simulations were critically analyzed: they turned out to be consistent with the stated objectives and methods, even in the context of the existing literature. The paper concludes by discussing the limitations and potential improvements of the research.
Keywords: ARDS , bronchial tree , CFD , parametric modelling
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In vivo validation of highly customized cranial Ti-6AL-4V ELI prostheses fabricated through incremental forming and superplastic forming: an ovine model study
Scientific Reports, 14(1)
Abstract
Cranial reconstructions are essential for restoring both function and aesthetics in patients with craniofacial deformities or traumatic injuries. Titanium prostheses have gained popularity due to their biocompatibility, strength, and corrosion resistance. The use of Superplastic Forming (SPF) and Single Point Incremental Forming (SPIF) techniques to create titanium prostheses, specifically designed for cranial reconstructions was investigated in an ovine model through microtomographic and histomorphometric analyses. The results obtained from the explanted specimens revealed significant variations in bone volume, trabecular thickness, spacing, and number across different regions of interest (VOIs or ROIs). Those regions next to the center of the cranial defect exhibited the most immature bone, characterized by higher porosity, decreased trabecular thickness, and wider trabecular spacing. Dynamic histomorphometry demonstrated differences in the mineralizing surface to bone surface ratio (MS/BS) and mineral apposition rate (MAR) depending on the timing of fluorochrome administration. A layer of connective tissue separated the prosthesis and the bone tissue. Overall, the study provided validation for the use of cranial prostheses made using SPF and SPIF techniques, offering insights into the processes of bone formation and remodeling in the implanted ovine model.
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Model-predicted effect of radial flux distribution on oxygen and glucose pericellular concentration in constructs cultured in axisymmetric radial-flow packed-bed bioreactors
Biocybernetics and Biomedical Engineering
Virtual prototyping and digital twin
Abstract
Radial flow packed-bed bioreactors (rPBBs) overcome the transport limitations of static and axial-flow perfusion bioreactors and enable development of clinical-scale bioengineered tissues. We developed criteria to design rPBBs with uniform medium radial flux distribution along bioreactor length ensuring uniform construct perfusion. We report a model-based analysis of the effect of non-uniform axial distribution of medium radial flux on pericellular concentration of oxygen and glucose. Albeit pseudo-homogeneous, the model predicts how medium flux, solutes transport and cellular consumption interact and determine the pericellular oxygen and glucose concentrations in the presence of pore transport resistance to design optimal axisymmetric rPBBs and enable control of pericellular environment. Thus, oxygen and glucose supply may match cell requirements as tissue matures. Flow and solute transport in bioreactor empty spaces and construct was described with Navier-Stokes and Darcy-Brinkman equations, and with convection–diffusion and convection–diffusion-reaction equations, respectively. Solute transport in construct accounted for Michaelian cellular consumption and bulk medium-to-cell surface oxygen transport resistance in terms of a transport-equivalent bed of Raschig rings. The effect of relevant dimensionless groups on pericellular and bulk solute concentrations was predicted under typical tissue engineering operation and evaluated against literature data for bone tissue engineering. Axial distribution of medium radial flux influenced the distribution of pericellular solutes concentration, more so at high cell metabolic activity. Increasing medium feed flow rates relieved non-uniform solute concentration distribution and decayed at cell surface for metabolic consumption, also starting from axially non-uniform radial flux distribution. Model predictions were obtained in runtimes compatible with on-line control strategies.
Keywords: Glucose , Model , Oxygen , Radial-flow packed-bed bioreactor , Tissue engineering , Transport