Janaina Dernowsek

From 3D Bioprinters to a fully integrated Organ Biofabrication Line

About 30 years ago, the 3D printing technique appeared. From that time on, engineers in medical science field started to look at 3D printing as a partner. Firstly, biocompatible and biodegradable 3D structures for cell seeding called scaffolds were fabricated for in vitro and in vivo animal trials. The advances proved to be of great importance, but, the use of scaffolds faces some limitations, such as low homogeneity and low density of cell aggregates. In the last decade, 3D bioprinting technology emerged as a promising approach to overcome these limitations and as one potential solution to the challenge of organ fabrication, to obtain very similar 3D human tissues, not only for transplantation, but also for drug discovery, disease research and to decrease the usage of animals in laboratory experimentation. 3D bioprinting allowed the fabrication of 3D alive structures with higher and controllable cell density and homogeneity. Other advantage of biofabrication is that the tissue constructs are solid scaffold-free. This paper presents the 3D bioprinting technology; equipment development, stages and components of a complex Organ Bioprinting Line (OBL) and the importance of developing a Virtual OBL.

Modeling and Simulation of Diffusion Process in Tissue Spheroids Encaged into Microscaffolds (Lockyballs)

Abstract Nutrition, organization, growth and signal transduction in cells are largely determined by diffusion mechanisms. The complex three-dimensional shapes of cellular environment complicate the experimental analysis and computational simulation of diffusion in live cells. Three-dimensional cell aggregates are called tissue spheroids and they are widely used in the field of tissue engineering because emulate in vivo microenvironments more accurately than conventional monolayer cultures. The greater contact of the cells with the culture medium is directly related to oxygen diffusion and thereafter with the cell viability and the increase of proliferation rate. Due to the characteristics of a 3D environment, at some zones within the tissue spheroids the cells are not equally exposed to the culture medium, and the result of an insufficient supply of oxygen to the cell impact in the formation of microenvironments with decreased oxygen, nutrients and soluble factors produced by cellular metabolism leading to the formation of low proliferation areas and consequently hypoxia and necrosis (cell death). The fusion of cells also changes the catabolites flow, generating a very heterogeneous diffusion. The idea of this work is to develop and improve microscaffolds based on the concept of lockyballs that have cell support function for tissue engineering. These microscaffolds are composed by hooks (which attach to other hooks or loops of neighbor lockyballs), loops (elevated pentagons, which allows hooks attaching) and tubes (that preventing entry of cells). It is presented one original type of lockyball (control) which has no internal structure (it is a hollow structure) further other three types of lockyballs. The first model has a spherical outer structure and inner hollow microsphere constituted by pores with diameters smaller than the cell ones, whose function would be to prevent cell entry. The second model has tubes constituted by pores and the third model has a spiral tube constituted by pores too. These inner structures provide an environment suitable to the diffusion gradient necessary for the cell viability of the spheroid avoiding necrosis. The first stage of the work consisted on the generation of different three-dimensional models by Computer Aided Design (CAD) software Rhinoceros 5.0. At the second stage, the CAD model was imported into volume element method (VEM) software (Star-CCMxa0+/CD-Adapco) to perform computational fluid simulation (CFD). The CFD simulations were essential to predict the diffusion phenomenon inside the whole 3D structure. The development of new microscaffolds models can enhance the regenerative capacity and 3D tissues construction.

Estratégias In Silico para Biofabricação de Órgãos em Impressoras 3D

Resumo Este trabalho propõe um blueprint interdisciplinar para a biofabricação de órgãos que utiliza as ideias comuns de simulações como métodos probabilísticos preditivos e cálculos de energia aplicados a dois frameworks: o mecânico e o biológico. Em resumo, o mecânico utilizaria a análise de elementos finitos para observar comportamentos fluidodinâmicos como pressão hidrostática, elasticidade e fluxo de fluidos. Já o biológico utilizaria sistemas complexos de interação intra, inter e extracelular para analisar comportamentos como divisão celular, difusão e quimiotaxia das unidades básicas que compõem o órgão.

BioCAE: A New Strategy of Complex Biological Systems for Biofabricationof Tissues and Organs

Biofabrication as an interdisciplinary area is fostering new knowledge and integration of areas like nanotechnology, chemistry, biology, physics, materials science, control systems, among many others, necessary to accomplish the challenge of bioengineering functional complex tissues. The emergence of integrated platforms and systems biology to understand complex biological systems in multiscale levels will enable the prediction and creation of biofabricated biological structures. This systematic analysis (meta-analysis) or integrated platforms for estimating biological process have been named as BioCAE, which will become the key for important steps of the biofabrication processes. Biological Computational Aided Engineering (BioCAE) is a new computational approach to understanding and bioengineer complex tissues (biofabrication) using a combination of different methods as multiscale modelling, computer simulations, data mining and systems biology. In addition, multi-agent systems (MAS), which are composed of different interacting computing entities called agents, also provide an interesting way to design and implement simulations of biological systems, integrating them with all steps of the BioCAE. MAS as a part of computational science have become a growing area to manipulate and solve complex problems. This paper presents an approach that will allow predicting the development and behavior of different biological processes such as molecular networks, gene interactions, cells, tissues and organs due to its flexibility, beyond to provide a new outlook in the biofabrication of tissues and organs.

3D Modelling and Structural Simulation of Scaffolds for Cardiovascular Implants

Cardiovascular disease remains as one of the main problems in contemporary health care worldwide. Several studies of the cardiac prostheses have been held since 60s with the advent of cardiopulmonary bypass. The mechanical properties of blood vessels, arteries and valves depend on collagen and elastic fibers, as well as on smooth muscle cells and ground substances. Many works about three-dimensional finite element model of the arterial wall segment and the heart valves assume the biological material to be homogeneous and isotropic. This configuration is a simplified way to reduce the complexity of biological structures. The primary purpose of this study was to assess the effects of fiber design and orientation on the stress distribution in a 3D model for cardiovascular implants and predict the elastic modulus of scaffolds designed.