STRUCTURAL DETERMINISTIC MODELING DESIGN AND FABRICATION OF ELECTROSPUN SCAFFOLDS FOR SOFT TISSUE ENGINEERING

The research fields of tissue engineering, biomechanics and regenerative medicine continue to evolve in response to the ever growing need for tissue replacement options. These fields aim to restore, maintain, or improve tissue or whole organ function. This doctoral studies focus on the development and experimental validation of a structural deterministic modeling strategy to: A) guide tissue engineering scaffold design, B) provide a better understanding of cellular mechanical and metabolic response to local micro-structural deformations. Targeted clinical application was the pulmonary heart valve. Electrospinning was selected as the optimal platform technology to implement, validate and test the presented designing strategy. An innovative custom made software was developed and tested on Electrospun poly (ester urethane) urea scaffolds (ES-PEUU), decellularized native tissues and collagen gels to fully characterized engineered constructs morphology. These structural information were adopted to feed and assist the mechanical modeling Two previously unevaluated fabrication modalities were investigated throughout both mechanical testing and image analysis in order to explore further how the electrospinning fabrication process can alter the structure and mechanical response: variation of mandrel translation velocity and concurrent electrospraying of cell culture medium with or without cells or rigid particulates. These fabrication parameters were studied to enrich control in the electrospinning process. 8 The detected material topology and mechanical equi-biaxial data were adopted to generate statistically equivalent scaffold mechanical models. The structural determinist approach was applied to ES-PEUU scaffolds, validated and mechanical response at organ and cell level was produced through FEM simulation. Prediction included: membrane tension vs. stretch relation, elasticity moduli, Nuclear Aspect Ratio vs. stretch relation for the cells micro-integrated into the scaffold. A three weeks in vivo - study on an ovine model was performed to demonstrated the feasibility of the adoption of ES-PEUU for TEHVs and more generally this material potential for soft tissue regeneration. Explants analysis showed surgical feasibility and acceptable valve functionality. The developed design strategies combining image analysis and structural deterministic modeling enabled the material topology to be both quantified and reproduced. Material fabrication parameters were related to material micro-architecture Similarly, the micro-architecture was related to macro scale mechanical responses such as in-plane reactions or flexural rigidity, and complex meso – micro scales mechanisms such NAR – stretch relation. In conclusion, the modeling approach introduced in this work bridges for the first time the scaffold fabrication parameters with the mechanical response at different scale length. The developed paradigm will be utilized to identify the optimal scaffold for a given soft tissue engineering application

Simulation of the spatial structure and cellular organization evolution of cell aggregates arranged in various simple geometries, using a kinetic monte carlo method applied to a lattice model

ilustraciones, graficasEsta tesis trata los modelos de morfogénesis, en particular los modelos de evolución guiada por contacto que son coherentes con la hipótesis de la adhesión diferencial. Se presenta una revisión de algunos modelos, sus principios biológicos subyacentes, la relevancia y aplicaciones en el marco de la bioimpresión, la ingeniería de tejidos y la bioconvergencia. Luego, se presentan los detalles de los modelos basados en métodos de Monte Carlo para profundizar más adelante en el modelo basados en algoritmos Kinetic Monte Carlo (KMC) , más específicamente, se describe en detalle un modelo KMC de autoaprendizaje (SL-KMC). Se presenta y explica la estructura algorítmica del código implementado, se evalúa el rendimiento del modelo y se compara con un modelo KMC tradicional. Finalmente, se realizan los procesos de calibración y validación, se observó que el modelo es capaz de replicar la evolución del sistema multicelular cuando las condiciones de energía interfacial del sistema simulado son similares a las del sistema de calibraciones. (Texto tomado de la fuente)This thesis treats the models for morphogenesis, in particular the contact-guided evolution models that are coherent with the differential adhesion hypothesis. A review of some models, their biological underpinning principles, the relevance and applications in the framework of bioprinting, tissue engineering and bioconvergence are presented. Then the details for the Monte Carlo methods-based models are presented to later deep dive into the Kinetic Monte Carlo (KMC) based model, and more specifically a Self-Learning KMC (SL-KMC) model is described to detail. The algorithmic structure of the implemented code is presented and explained, the model performance is assessed and compared with a traditional KMC model. Finally, the calibration and validation processes have been carried out, it was observed that the model is able to replicate the multicellular system evolution when the interfacial energy conditions of the simulated system are similar to those of the calibrations system.MaestríaMagíster en Ingeniería - Ingeniería Químic

Additively manufactured metallic biomaterials

Metal additive manufacturing (AM) has led to an evolution in the design and fabrication of hard tissue substitutes, enabling personalized implants to address each patient's specific needs. In addition, internal pore architectures integrated within additively manufactured scaffolds, have provided an opportunity to further develop and engineer functional implants for better tissue integration, and long-term durability. In this review, the latest advances in different aspects of the design and manufacturing of additively manufactured metallic biomaterials are highlighted. After introducing metal AM processes, biocompatible metals adapted for integration with AM machines are presented. Then, we elaborate on the tools and approaches undertaken for the design of porous scaffold with engineered internal architecture including, topology optimization techniques, as well as unit cell patterns based on lattice networks, and triply periodic minimal surface. Here, the new possibilities brought by the functionally gradient porous structures to meet the conflicting scaffold design requirements are thoroughly discussed. Subsequently, the design constraints and physical characteristics of the additively manufactured constructs are reviewed in terms of input parameters such as design features and AM processing parameters. We assess the proposed applications of additively manufactured implants for regeneration of different tissue types and the efforts made towards their clinical translation. Finally, we conclude the review with the emerging directions and perspectives for further development of AM in the medical industry.National Institutes of Health || The Natural Sciences and Engineering Research Council of Canada || Network for Holistic Innovation in Additive Manufacturin

Advanced Applications of Rapid Prototyping Technology in Modern Engineering

Rapid prototyping (RP) technology has been widely known and appreciated due to its flexible and customized manufacturing capabilities. The widely studied RP techniques include stereolithography apparatus (SLA), selective laser sintering (SLS), three-dimensional printing (3DP), fused deposition modeling (FDM), 3D plotting, solid ground curing (SGC), multiphase jet solidification (MJS), laminated object manufacturing (LOM). Different techniques are associated with different materials and/or processing principles and thus are devoted to specific applications. RP technology has no longer been only for prototype building rather has been extended for real industrial manufacturing solutions. Today, the RP technology has contributed to almost all engineering areas that include mechanical, materials, industrial, aerospace, electrical and most recently biomedical engineering. This book aims to present the advanced development of RP technologies in various engineering areas as the solutions to the real world engineering problems

NASA Tech Briefs, August 2011

Topics covered include: Miniature, Variable-Speed Control Moment Gyroscope; NBL Pistol Grip Tool for Underwater Training of Astronauts; HEXPANDO Expanding Head for Fastener-Retention Hexagonal Wrench; Diagonal-Axes Stage for Pointing an Optical Communications Transceiver; Improvements in Speed and Functionality of a 670-GHz Imaging Radar; IONAC-Lite; Large Ka-Band Slot Array for Digital Beam-Forming Applications; Development of a 150-GHz MMIC Module Prototype for Large-Scale CMB Radiation; Coupling Between Waveguide-Fed Slot Arrays; PCB-Based Break-Out Box; Multiple-Beam Detection of Fast Transient Radio Sources; Router Agent Technology for Policy-Based Network Management; Remote Asynchronous Message Service Gateway; Automatic Tie Pointer for In-Situ Pointing Correction; Jitter Correction; MSLICE Sequencing; EOS MLS Level 2 Data Processing Software Version 3; DspaceOgre 3D Graphics Visualization Tool; Metallization for Yb14MnSb11-Based Thermoelectric Materials; Solvent/Non-Solvent Sintering To Make Microsphere Scaffolds; Enhanced Fuel-Optimal Trajectory-Generation Algorithm for Planetary Pinpoint Landing; Self-Cleaning Coatings and Materials for Decontaminating Field-Deployable Land and Water-Based Optical Systems; Separation of Single-Walled Carbon Nanotubes with DEP-FFF; Li Anode Technology for Improved Performance; Post-Fragmentation Whole Genome Amplification-Based Method; Microwave Tissue Soldering for Immediate Wound Closure; Principles, Techniques, and Applications of Tissue Microfluidics; Robotic Scaffolds for Tissue Engineering and Organ Growth; Stress-Driven Selection of Novel Phenotypes; Method for Accurately Calibrating a Spectrometer Using Broadband Light; Catalytic Microtube Rocket Igniter; Stage Cylindrical Immersive Display; Vacuum Camera Cooler; Atomic Oxygen Fluence Monitor; Thermal Management Tools for Propulsion System Trade Studies and Analysis; Introduction to Physical Intelligence; Technique for Solving Electrically Small to Large Structures for Broadband Applications; Accelerated Adaptive MGS Phase Retrieval; Large Eddy Simulation Study for Fluid Disintegration and Mixing; Tropospheric Correction for InSAR Using Interpolated ECMWF Data and GPS Zenith Total Delay; Technique for Calculating Solution Derivatives With Respect to Geometry Parameters in a CFD Code; Acute Radiation Risk and BRYNTRN Organ Dose Projection Graphical User Interface; Probabilistic Path Planning of Montgolfier Balloons in Strong, Uncertain Wind Fields; Flight Simulation of ARES in the Mars Environment; Low-Outgassing Photogrammetry Targets for Use in Outer Space; Planning the FUSE Mission Using the SOVA Algorithm; Monitoring Spacecraft Telemetry Via Optical or RF Link; and Robust Thermal Control of Propulsion Lines for Space Missions

Doctor of Philosophy

dissertationAngiogenesis is the process by which new blood vessels sprout from existing vessels, enabling new vascular elements to be added to an existing vasculature network. Mechanical interactions during angiogenesis, i.e., traction forces applied by neovessels and the corresponding deformation of the extracellular matrix (ECM), are important regulators of growth and neovascularization. However, the dynamic relationship between cell-generated forces, the deformation of the ECM, and the topology of the emerging vascular network are poorly understood. The goal of this research was to develop, implement, and validate a computational framework that simulates the dynamic mechanical interaction between angiogenic neovessels and the ECM. This dissertation presents a novel continuous-discrete finite element (FE) model with angiogenic growth coupled with matrix deformation. Angiogenesis was simulated using a discrete growth model. This model uses properties of the ECM, represented by a continuous FE mesh, to regulate angiogenic growth and branching and was capable of accurately predicting vascular morphometric data when simulating growth in various matrix conditions. To couple growth with matrix deformation, sprout forces were applied to the mesh and the corresponding deformation of the matrix was determined using the nonlinear FE software FEBio. This deformation was then used to update the ECM into the current configuration before calculating the next growth step. Data from vascularized gel experiments were used to both calibrate mechanisms within the model during implementation and compare with computational simulations to assess the validity of the simulations. In simulations of experiments involving vascularized collagen gels subjected to various mechanical boundary constraints, this coupled framework accurately predicted gel contraction and microvessel alignment for each condition. The primary mechanism for alignment occurs as microvessels passively align while moving with the deformation of the surrounding matrix. These results demonstrate how biomechanical cellular activity at the microscale during morphogenic processes such as angiogenesis can influence the macroenvironment and induce patterns and organization. These methods provide a flexible computational platform to investigate the mechanisms by which the biomechanical interaction between cells and the ECM regulates the structure and composition of the emerging tissue during morphogenesis

Computational Modeling of Fracture Failure in Mineralized and Prosthetic Biomaterials

Natural mineralized tissues, e.g., teeth and bone, have the capacity to tolerate the daily physiological loading. However, due to their high mineralized composition, they have been recognized as a class of relatively brittle biomaterials. The inherent brittle nature and fairly high susceptibility to mechanical failure present a more critical problem in biomedical research field. To replace such diseased or damaged mineralized tissues, prosthetic materials are largely applied in the areas of dental and osteo clinical treatments. Ceramic materials provide numerous favourable characteristics, including biocompatibility and chemical resistance. In addition to the dental industry, applications of osteofixation/osteosynthiesis devices are considered fundamental to stabilize various treatments of bone defects for promoting osteointegration and reconstruction. However, clinical observations and specialized literature have revealed that dental restorative materials and prosthetic fixation devices are often subject to high stress, leading to fracture either by catastrophic overloading or cyclic fatigue failure. The aim of this thesis is to develop a computational modelling framework on the basis of the extended finite element method (XFEM) to investigate the fracture behaviors of mineralised and synthetic biomaterials in various medical applications. The XFEM modelling results are validated by being compared with the in-vitro experiments and/or clinical observations. Through the research in this thesis studies, XFEM has been demonstrated to be a powerful tool to analyse fracture behaviors in the bio-structures subjected to not only static loadings but also cyclic loadings. The outcomes generated in this thesis help gain some insightful understanding failure of the native or prosthetic structures, which is anticipated to provide some clinical guidelines for the design optimisation of patient-specific prosthetic devices to ensure their reliability and longevity