Presented work deals with Biomechanical study of the facial skeleton. This work is focused on the fixation of the mandible after removal of a tumor from affected bone tissue. The aim of the work is to perform biomechanical study of the facial skeleton with subsequent detailed stress strain analysis of two mandible implants designed and manufactured for specific patients. The geometry model of mandible used for design of mandible implants and used for computational modelling has been obtained on the basis of CT data of two patients. A Theoretical-Clinical sub-study that deals with the comparison the CT data processing which is necessary for creating the model of geometry is a part of the thesis. Two models of mandible with applied mandible implant have been created for two specific patients with tumorous mandible bone tissue. Stress strain analysis has been performed for these two models. Results of the stress strain analysis of two models of mandibles with mandible implants are presented in the final chapters of the thesis. Findings of the biomechanical study have been published and applied in clinical practice.

Deux méthodes d’assistance opératoire, pour le positionnement du composant glénoïdien d’une prothèse d’épaule, sont explorées. Elles ont pour dénominateur commun une reconstruction 3D première de la glène pathologique à implanter. Une approche essentiellement clinique, avec des travaux d’application pratique, est proposée pour la technologie des Patients Specific Implants (PSI), dont l’utilisation en orthopédie est croissante. Une approche davantage technologique est ensuite proposée, de type Réalité Augmentée, jusqu’à maintenant encore inexploitée dans le champ de la chirurgie orthopédique. La faisabilité de cette approche, les conditions d’emploi des technologies inhérentes, ont été étudiées. En amont, un nouveau type d’information pour implémenter, sur le support connecté (lunettes électroniques), l’application de réalité, est proposé, avec la modélisation mathématique par régression linéaire multiple d’une glène normale. L’objectif secondaire est d’obtenir une banque de données dites de glènes génériques normales, pouvant servir de référence à la reconstitution d’une glène pathologique à traiter, après un processus de morphing. / In this thesis, two methods of operating assistance for the positioning of the glenoid component of a shoulder prosthesis, are addressed. They have in common a preliminary 3D reconstruction of the pathological glenoid to implant. A main clinical approach, with practice studies, is proposed for the Patient Specific Implants technology, which is currently used in orthopaedics. Then a main prospective and technological approach is proposed with the Augmented Reality, while it is so far untapped in the field of orthopaedic surgery. The feasibility of this last technology, as well as the tools and the manual for its use, were studied. Upstream, a new type of information to implement the augmented reality connected application support is offered, with mathematical modeling by multiple linear regression of a normal glenoid. The second goal is to build a normal generic glenoids database. It can be used as reference to the reconstruction of a pathological glenoid to treat, after a morphing process step.

Thesis (PhD (Industrial Engineering))--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: Back pain is a common concern amongst a growing population of people across the world today, where in most cases the pain can become unbearable resulting in major lifestyle adjustments. Seventy to eighty percent of the population of the Western world experiences low-back pain at one time or another. Pain can be produced as a worn disc becomes thin, narrowing the space between the vertebrae. Pieces of the damaged disc may also break off and cause irritation to the nerves signalling back pain. Depending on the severity of a patient’s condition, and after conservative treatment options have been exhausted, a disc replacement surgery (arthroplasty) procedure may be prescribed to restore spacing between vertebrae and relieve the pinched nerve, while still maintaining normal biomechanical movement. Typical complications that are however still observed in some cases of disc implants include: anterior migration of the disc, subsidence (sinking of disc) and lateral subluxation (partial dislocation of a joint). Issues such as function, correct placement and orientation, as well as secure fixation of such a disc implant to the adjacent vertebrae are highly important in order to replicate natural biomechanical behaviour and minimise the occurrence of the complications mentioned. As various imaging and manufacturing technologies have developed, the option for individual, patientspecific implants is becoming more of a practical reality than it has been in the past. The combination of CT images and Rapid Manufacturing for example is already being used successfully in producing custom implants for maxilla/facial and cranial reconstructive surgeries. There exists a need to formalise a process chain for the design and manufacture of custom-made intervertebral disc implants and to address the issues involved during each step. Therefore this study has investigated the steps involved for such a process chain and the sensible flow of information as well as the use of state-of-the-art manufacturing technologies. Strong emphasis was placed on automation of some of the processes as well as the user-friendliness of software where engineers and surgeons often need to work together during this multi-disciplinary environment. One of the main benefits for customization was also investigated, namely a reduction in the risk and potential for implant subsidence. Stiffness values from pressure tests on vertebrae were compared between customized implants and implants with flat endplate designs. Results indicated a statistically significant improvement of customized, endplate matching implants as opposed to flat implant endplates. Therefore it may be concluded that the use of customized intervertebral disc implants with patient specific endplate geometry may decrease the risk and potential for the occurrence of subsidence. / AFRIKAANSE OPSOMMING: Rugpyn is ‘n algemene bekommernis vir ‘n groeiende populasie van mense in die wêreld vandag, waar in meeste gevalle die pyn ondraagbaar kan raak en groot leefstyl aanpassings vereis. Sewentig tot tagtig persent van die populasie in die Westerse wêreld ondervind lae rugpyn op een of ander stadium. Die pyn kan veroorsaak word deur ‘n intervertebrale skyf wat verweer en dunner word, en veroorsaak dat die spasie tussen die vertebrae vernou. Stukkies van die beskadigde skyf mag ook afbreek en irritasie aan die senuwees veroorsaak wat verdere pyn kan veroorsaak. Afhangende van die ernstigheid van ‘n pasiënt se geval, en nadat opsies vir konservatiewe behandeling uitgeput is, kan ‘n skyf vervangings-prosedure (artroskopie) voorgeskryf word om die spasie tussen die vertebrae te herstel en sodoende die geknypte senuwee te verlos. Die skyf vervanging herstel spasiëring tussen vertebrae terwyl die normale biomeganiese beweging ook behoue bly, in teenstelling met ‘n fusieprosedure wat die betrokke vertebrae aanmekaar vasheg en normale beweging belemmer. Tipiese komplikasies wat egter steeds na ‘n skyf vervanging in sommige gevalle waargeneem word sluit in: anterior migrasie van die inplantaat, insinking, sowel as laterale sublukasie (gedeeltelike dislokasie van ‘n gewrig). Faktore soos funksie, korrekte posisionering en orientasie, sowel as vashegting van so ‘n skyf inplantaat tot die aanliggende vertebrale bene is besonder belangrik om natuurlike biomeganiese beweging te herstel en sodoende bogenoemde komplikasies te verminder. Soos wat verskeie beeldings- en vervaardigingstegnologië verbeter het oor die laaste dekade, het die moontlikheid vir individuele, pasiënt-spesifieke inplantate al hoe meer ‘n praktiese realiteit begin word. Die kombinasie van Gerekenariseerde Tomografie (GT), tesame met Snel Vervaardiging word byvoorbeeld reeds suksesvol aangewend tydens die ontwerp en vervaardiging van pasiënt-spesifieke inplantate vir maksilla- en kraniale rekonstruktiewe chirurgie. Daar bestaan egter ‘n behoefte om ‘n formele prosesketting vir die ontwerp en vervaardiging van pasiënt-spesifieke intervertebrale skyf inplantate te ontwikkel en om belangrike faktore tydens elke stap noukeurig te beskryf. Hierdie studie het na die verskillende stappe in die prosesketting gekyk om ‘n sinvolle vloei van informasie en benutting van hoë gehalte vervaardigingstegnologië saam te snoer. Sterk klem was gelê op outomatisering van prosesse asook gebruikersvriendelikheid van sagteware waar ingenieurs en medici dikwels saam moet werk tydens hierdie kruisdissiplinêre omgewing. Een van die hoof verwagte voordele met die gebruik van pasklaar skyf inplantate, naamlik die vermindering van moontlike insinking van die inplantaat in die been, is ook ondersoek. Die ondersoek het druktoetse behels en die vergelyking van ooreenstemmende styfheid tussen inplantate wat die kontoer van die bene volg teenoor gewone plat eindplate. Die resultate was statisties beduidend in die guns van die pasklaar inplantate wat die beenkontoere gevolg het, en bewys dus dat die risiko vir insinking verminder is.

Medical imaging technologies have allowed for in vivo evaluation of the human musculoskeletal system. With advances in both medical imaging and computing, patient-specific model development of anatomic structures is becoming a reality. Three-dimensional surface models are useful for patient-specific measurements and finite element studies. Orthopaedics is closely tied to engineering in the analysis of injury mechanisms, design of implantable medical devices, and potentially in the prediction of injury. However, a disconnection exists between medical imaging and orthopaedic analysis; whereby, the ability to generate three-dimensional models from an imaging dataset is difficult, which has restricted its application to large patient populations. We have compiled image processing, image segmentation, and surface generation tools in a single software package catered specifically to image-based orthopaedic analysis. We have also optimized an automated segmentation technique to allow for high-throughput bone segmentation and developed algorithms that help to automate the cumbersome process of mesh generation in finite element analysis. We apply these tools to evaluate graft placement in anterior cruciate ligament reconstruction in a multicenter study that aims to improve the patient outcomes of those that undergo this procedure.

Patient-specific multi-physics simulations have the potential to improve the diagnosis, treatment, and scientific inquiry of heart valve dynamics. It has been shown that the flow characteristics within the left ventricle are important to correctly capture the aortic and mitral valve motion and corresponding fluid dynamics, motivating the use of patient-specific imaging to describe the aortic and mitral valve geometries as well as the motion of the left ventricle (LV). The LV position can be captured at several time points in the cardiac cycle, such that its motion can be prescribed a priori as a Dirichlet boundary condition during a simulation. Valve leaflet motion, however, should be computed from soft-tissue models and incorporated using fully-coupled Fluid Structure Interaction (FSI) algorithms. While FSI simulations have in part or wholly been achieved by multiple groups, to date, no high-throughput models have been developed, which are needed for use in a clinical environment. This project seeks to enable patient-derived moving LV boundary conditions, and has been developed for use with a previously developed immersed boundary, fixed Cartesian grid FSI framework. One challenge in specifying LV motion from medical images stems from the low temporal resolution available. Typical imaging modalities contain only tens of images during the cardiac cycle to describe the change in position of the left ventricle. This temporal resolution is significantly lower than the time resolution needed to capture fluid dynamics of a highly deforming heart valve, and thus an approach to describe intermediate positions of the LV is necessary. Here, we propose a primarily Eulerian means of representing LV displacement. This is a natural extension, since an Eulerian framework is employed in the CFD model to describe the large displacement of the heart valve leaflets. This approach to using Eulerian interface representation is accomplished by applying “morphing” techniques commonly used in the field of computer graphics. For the approach developed in the current work, morphing is adapted to the unique characteristics of a Cartesian grid flow solver which presents challenges of adaptive mesh refinement, narrow band approach, parallel domain decomposition, and the need to supply a local surface velocity to the flow solver that describes both normal and tangential motion. This is accomplished by first generating a skeleton from the Eulerian interface representation, and deforming the skeleton between image frames to determine bulk displacement. After supplying bulk displacement, local displacement is determined using the Eulerian fields. The skeletons are also utilized to automate the simulation setup to track the locations upstream and downstream where the system inflow/outflow boundary conditions are to be applied, which in the current approach, are not limited to Cartesian domain boundaries.

No description available.

La lombalgie est un problème de santé commun qui touche une grande partie de la population des pays industrialisés. Au cours des années, la modélisation numérique a été largement étudiée pour étudier la biomécanique du rachis lombaire pour aider fortement les cliniciens dans le diagnostic et les traitements de cette pathologie. Ce travail présente une méthodologie pour la modélisation éléments finis spécifique au patient prenant en compte à la fois la géométrie individualisée et les propriétés des matériaux des structures biologiques. Dans cette étude, le maillage est piloté par des connaissances des matériaux personnalisées qui sont extraites de l'imagerie médicale avancée. En outre, un logiciel convivial comprenant du traitement d'images, des maillages « material-driven » et de l'affectation des propriétés des matériaux, nommé C3M pour le «Computed Material-driven Mesh Model», a été développé pour générer efficacement des modèles FE spécifiques aux sujets à partir d'images médicales. Ce procédé est appliqué pour générer un modèle FE spécifique au patient du rachis lombaire à partir d'images issues par Résonance Magnétique (IRM) ou par tomodensitométrie 3D (CT). Cette approche ouvre une nouvelle perspective pour améliorer le processus de maillage à l'aide de connaissances du matériel dérivées d'images médicales. Le modèle proposé permet un assemblage précis et simple de vertèbres et des disques intervertébraux en tenant en compte à la fois la géométrie et les propriétés mécaniques des matériaux reflétant la spécificité du patient. / Low back pain is a common health problem which impacts a large part of the population in industrialized countries. Over the years, numerical modeling has been widely studied to investigate the biomechanics of lumbar spine for strongly assisting clinicians in diagnosis and treatments of this spinal pathology. In recent years, there has been a growing interest in researching and developing patient specific computer modeling which has proven its ability to provide great promises for developing realistic model of individual subject. However, still the specificity of these models is not fully described or is often limited to patient geometry. In fact, few models consider appropriate material properties derived from tissue characterization obtained from medical images. Furthermore, patient specific models can be obtained with geometry and mechanical properties derived from CT, but few from MRI which is well-suited for examining soft tissues. Therefore, development of the high-fidelity, patient-specific finite element model of the lumbar spine still presents the challenge. In this context of patient-specific finite element modeling, mesh generation is a crucial issue which requires an accurate representation of the geometry with well-shaped and sized elements and a relevant distribution of materials. This work presents a methodology for patient-specific finite element modeling which takes both individualized geometry and material properties of biological structures into consideration. In this study, the mesh is driven by personalized material knowledge which is extracted from advanced medical imaging. Additionally, a user-friendly program including image processing, material-driven meshing and material properties assignment, named C3M for “Computed Material-driven Mesh Model”, has been developed to generate efficiently subject-specific FE models derived from medical images. This process is applied to generate a patient specific FE model of lumbar spine based on both MRI and CT images. This approach opens a new direction to improve the meshing process using material knowledge derived from medical images. The proposed model allows an accurate and straightforward assembly of vertebrae and IVDs considering both geometry and material properties reflecting patient-specificity.

No description available.

[EN] Chronic pain disease has 35-50% of prevalence worldwide. When drugs stop working, spinal cord stimulation (SCS) therapy is a non-drug alternative treatment for several conditions of chronic pain, such as neuropathic pain. In the last 40 years, SCS computational modeling has been the key tool to analyze and understand the effect of the stimulation parameters on neural response. However, the lack of realistic models limits the model-based predictions accuracy for SCS therapy optimization concerning the stimulation parameters management and the development of clinical applications. This thesis presents three improvements in SCS modeling from cellular to organic levels: · Cellular level: a human A -beta sensory myelinated nerve fiber model is shown. The model simulates the action potential creation and propagation of human sensory fibers produced by electrical stimulation. Moreover, to consider the current losses produced at the internodal compartments, a realistic myelin model is included. · Organic level: two spinal cord volume conductor models are presented. The first one is a generalized SCS model, which is based on in vivo 3T high-resolution magnetic resonance images from the human spinal cord, solving then one of the main limitations of previous SCS models, which is the inclusion of cadaveric measurements. The second one is a 3D patient-specific SCS model, which includes the entire spinal cord geometry variation of three different vertebral levels (T8, T9, and T10) from patients undergoing SCS treatment. This novel approach is validated clinically, showing that patient-specific modeling improves model-based predictions accuracy compared to generalized SCS models. In addition to this, this thesis presents three studies related to SCS therapy by using the three computational models developed previously: - Role of stimulation frequency: it is performed using the human A-beta sensory myelinated nerve fiber model. The outcome of this study showed that frequency could have a significant influence on the reduction or increase of the neuron activity, participating thus in the selection of the targeted neural elements in SCS therapy, in tonic stimulation. - Effect of electrode polarity: using the 3D generalized SCS model, the effect of the most used and known polarities (bipolar, guarded cathode, and dual-guarded cathode) is shown. The results showed that, unlike guarded cathode, dual-guarded cathode maximized the activating area and depth in dorsal columns, also increasing the probability of activating dorsal roots fibers. - Clinical applications: the pre-implantation selection of the electrode polarity was performed with the 3D patient-specific model. The findings showed that this clinical application could determine the electrode configurations that best overlapped paresthesia coverage to the painful dermatomes of the patient before the SCS device implant. On the other hand, the effect of offset electrodes was also investigated. In this case, the results revealed that staggered offset placement canceled the left- or right-activation displacement in the dorsal columns, suggesting that offset electrodes placement should be avoided in tonic stimulation. / [ES] El dolor crónico es una enfermedad que tiene una prevalencia de entre el 35% y el 50% de la población mundial. Cuando los fármacos dejan de hacer efecto, la terapia de estimulación de médula espinal (EME) es una alternativa no farmacológica que se usa para el tratamiento de diversas condiciones de dolor crónico, como el dolor neuropático. En los últimos 40 años, el modelado computacional de la EME ha sido la herramienta clave para analizar y entender el efecto de los parámetros de estimulación eléctrica en la respuesta neuronal. Sin embargo, la falta de modelos realistas limita la precisión de las predicciones de los modelos para la optimización de la terapia de EME, en referencia a la programación de los parámetros de estimulación y el desarrollo de aplicaciones clínicas. Esta tesis presenta tres mejoras en el modelado computacional de la terapia de EME, desde el nivel celular hasta el nivel orgánico: · Nivel celular: se presenta un modelo de fibra mielínica A-beta sensitiva humana. El modelo simula la creación y propagación del potencial de acción de fibras humanas sensitivas que se produce bajo el efecto de un estímulo eléctrico. Además, con el fin de considerar las pérdidas de corriente producidas en los compartimentos internodales, la mielina se modeliza de forma realista. · Nivel orgánico: se presentan dos modelos de conductor volumétrico de médula espinal. El primero se trata de un modelo de EME generalizado, el cual está basado en imágenes de resonancia magnética de 3T de alta resolución de médula espinal humana obtenidas in vivo. Esta propuesta resuelve una de las principales limitaciones presente en modelos de EME anteriores, que es la inclusión de medidas geométricas obtenidas de cadáveres. El segundo modelo es un modelo tridimensional personalizado al paciente, el cual incluye la variación de la geometría de la médula espinal en tres niveles vertebrales diferentes (T8, T9 y T10) a partir de pacientes sometidos al tratamiento de EME. Esta novedosa propuesta es validada clínicamente, mostrando además que el modelado computacional personalizado mejora la precisión de las predicciones del modelo en comparación a un modelo generalizado. Además, esta tesis presenta tres estudios relacionados con la terapia de EME usando los tres modelos desarrollados previamente: - El papel de la frecuencia de estimulación: se realiza mediante el uso del modelo de fibra mielínica A -beta sensitiva humana. Los resultados de este estudio muestran que la frecuencia podría tener una influencia significante en la reducción o aumento de la actividad de la neurona, participando de este modo en la selección de los elementos neurales objetivo en la terapia de EME, en estimulación tónica. - Efecto de la polaridad del electrodo: usando el modelo 3D generalizado de EME, se muestra el efecto de las polaridades más conocidas y usadas: bipolar, cátodo guardado y doble-cátodo guardado. Los resultados muestran que, a diferencia del cátodo guardado, la polaridad de doble-cátodo guardado maximiza el área y profundidad de activación en los cordones posteriores, aumentando también la probabilidad de activar las fibras de las raíces dorsales. - Aplicaciones clínicas: usando el modelo 3D personalizado al paciente, se ha realizado la selección pre-implante de la polaridad del electrodo. Los resultados muestran que esta aplicación clínica podría determinar las configuraciones de electrodos que mejor solapan la cobertura de parestesia con los dermatomas dolorosos del paciente antes del implante del dispositivo de EME. Por otro lado, también se ha estudiado el efecto de la posición escalonada de los electrodos en el paciente. En este caso, los resultados revelan que el posicionamiento escalonado cancela el desplazamiento izquierdo o derecho de la activación neuronal en los cordones posteriores, sugiriendo así que el posicionamiento escalonado debería evitarse cuando se aplica la estimu / [CAT] El dolor crònic es una enfermetat amb una prevalència d'entre el 35% i el 50% de la població mundial. Quan els fàrmacs deixen de fer efecte, la teràpia d'estimulació de mèdul·la espinal (EME) és una alternativa no farmacològica que s'usa per al tractament de diverses condicions de dolor crònic, com el dolor neuropàtic. En els últims 40 anys, el modelatge computacional de l'EME ha sigut la ferramenta clau per a analitzar i entendre l'efecte dels paràmetres d'estimulació elèctrica en la resposta neuronal. No obstant això, la falta de models realistes limita la precisió de les prediccions dels models per a l'optimizació de la teràpia d'EME, en referència a la programació dels paràmetres d'estimulació i el desenvolupament d'aplicacions clíniques. Esta tesi presenta tres millores en el modelatge computacional de la teràpia d'EME, des del nivell cel·lular fins al nivell orgànic: · Nivell cel·lular: es presenta un model de fibra mielínica A-beta sensitiva humana. El model simula la creació i propagació del potencial d'acció de fibres humanes sensitives que es produeix baix l'efecte d'un estímul elèctric. A més a més, amb la finalitat de considerar les pèrdues de corrent produïdes als compartiments internodals, la mielina es modela de forma realista. · Nivell orgànic: es presenten dos models de conductor volumètric de mèdul·la espinal. El primer es tracta d'un model d'EME generalitzat, el qual es basa en imatges de ressonància magnètica de 3T d'alta resolució de mèdul·la espinal humana obtingudes in vivo. Esta proposta resol una de les principals limitacions present en models d'EME anteriors, que és la inclusió de mesures geomètriques obtingudes de cadàvers. El segon model és un model tridimensional personalitzat al pacient, el qual inclou la variació de la geometria de la mèdul·la espinal en tres nivells vertebrals diferentes (T8, T9 i T10) a partir de pacients sotmesos al tractament d'EME. Aquesta innovadora proposta és validada clínicament, demostrant també que el modelatge computacional personalitzat millora la precisió de les prediccions del model en comparació a un model generalitzat. A més, esta tesi presenta tres estudis relacionats amb la teràpia d'EME utilitzant els tres models desenvolupats prèviament: - El paper de la freqüència d'estimulació: es realitza mitjançant l'ús del model de fibra mielínica A-beta sensitiva humana. Els resultats d'este estudi mostren que la freqüència podria tindre una influència significant en la reducció o augment de l'activitat de la neurona, participant així en la selecció dels elements neurals objectiu en la teràpia d'EME, en estimulació tònica. - Efecte de la polaritat de l'elèctrode: usant el model 3D generalitzat d'EME, es mostra l'efecte de les polaritats més conegudes i utilitzades: bipolar, càtode guardat i doble-càtode guardat. Els resultats mostren que, a diferència del càtode guardat, la polaritat de doble-càtode guardat maximitza l'àrea i profunditat d'activació en els cordons posteriors, augmentant també la probabilitat d'activar les fibres de les arrels dorsals. - Aplicacions clíniques: usant el model 3D personalitzat al pacient, s'ha realitzat la selecció pre-implant de la polaritat de l'elèctrode. Els resultats mostren que esta aplicació clínica podria determinar les configuracions d'elèctrodes que millor solapen la cobertura de parestèsia amb els dermatomes dolorosos del pacient abans de l'implant del dispositiu d'EME. D'altra banda, també s'ha estudiat l'efecte de la posició esglaonada dels elèctrodes en el pacient. En este cas, els resultats revelen que el posicionament esglaonat cancel·la el desplaçament esquerre o dret de l'activació neuronal en els cordons posteriors, sugerint així que el posicionament esglaonat deuria evitar-se quan s'aplica l'estimulació tònica. / Solanes Galbis, C. (2021). Patient-specific computational modeling for spinal cord stimulation therapy optimization [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/176007 / TESIS

<p>Breast cancer affects 12.5\% of women over their life time and tissue expansion (TE) is the most common technique for breast reconstruction after mastectomy. However, the rate of complications with TE can be as high as 15\%. Even though the first documented case of TE happened in 1957, there has yet to be a standardized procedure established due to the variations among patients and the TE protocols are currently designed based on surgeon's experience. There are several studies of computational and theoretical framework modeling skin growth in TE but these tools are not used in the clinical setting. This dissertation focuses on bridging the gap between the already existing skin growth modeling efforts and it's potential application in the clinical setting.</p> <p><br></p> <p>We started with calibrating a skin growth model based on porcine skin expansions data. We built a predictive finite element model of tissue expansion. Two types of model were tested, isotropic and anisotropic models. Calibration was done in a probabilistic framework, allowing us to capture the inherent biological uncertainty of living tissue. We hypothesized that the skin growth rate was proportional to stretch. Indeed, the Bayesian calibration process confirmed that this conceptual model best explained the data. </p> <p><br></p> <p>Although the initial model described the macroscale response, it did not consider any activity on the cellular level. To account for the underlying cellular mechanisms at the microscopic scale, we have established a new system of differential equations that describe the dynamics of key mechanosensing pathways that we observed to be activated in the porcine model. We calibrated the parameters of the new model based on porcine skin data. The refined model is still able to reproduce the observed macroscale changes in tissue growth, but now based on mechanistic knowledge of the cell mechanobiology.  </p> <p><br></p> <p>Lastly, we demonstrated how our skin growth model can be used in a clinical setting. We created TE simulations matching the protocol used in human patients and compared the results with clinical data with good agreement. Then we established a personalized model built from 3D scans of a patient unique geometry. We verified our model by comparing the skin growth area with the area of the skin harvested in the procedure, again with good agreement.</p> <p><br></p> <p>Our work shows that skin growth modeling can be a powerful tool to aid surgeons design TE procedures before they are actually performed. The simulations can help with optimizing the protocol to guarantee the correct amount of skin is growth in the shortest time possible without subjecting the skin to deformations that can compromise the procedure.</p>