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Computational and mathematical methods to study complex models at several levels of biological organization – BioCAE – (molecules, genes, mRNAs, proteins, metabolic networks, cells, organoids, tissues, and organs), which can be adapted to predict the development of a tissue and/or organ in many steps of the biofabrication.
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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 unde...
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... aim of multi-scale modelling is to represent, predict and understand the behaviour of complex systems across, not only in a wide spatial scale (molecules, genes, mRNAs, proteins, metabolic networks, cells, organoids, tissues and organs) as shown in Figure 2, but also in temporal scale (seconds (s), minutes (min), hours (h), days, weeks, months, years). Despite the significant growth of this field of knowledge, there is a need to develop frameworks for the interoperability among different simulation software. ...Citations
... So far, researchers have strived to optimize path planning targeted at IOB [40,41], including printing on a free-moving hand anatomy using motion tracking [42,43]. In the future, machine learning can be used to automatically generate optimal bioprinting strategies [44][45][46][47]. The integration of 3D scanner with a fixed relative coordinate to the robotic arm is also required to eliminate the need of prebioprinting calibration to minimize total processing time. ...
3D bioprinting directly into injured sites in a surgical setting, intraoperative bioprinting (IOB), is an effective process, in which the defect information can be rapidly acquired and then repaired via bioprinting on a live subject. In patients needing tissue resection, debridement, traumatic reconstruction, or fracture repair, the ability to scan and bioprint immediately following surgical preparation of the defect site has great potential to improve the precision and efficiency of these procedures. In this opinion article, we provide the reader with current major limitations of IOB from engineering and clinical points of view, as well as possibilities of future translation of bioprinting technologies from bench to bedside, and expound our perspectives in the context of IOB of composite and vascularized tissues.
... 31 Bio-CAM research not only provides a fast way to check design feasibility but also gives a chance to better understand the physical and chemical principles governing printing (Fig. 2, step 4). 12,32 Through control language and protocols, such as RS 274 (G-Code; Massachusetts Institute of Technology, Cambridge, MA) and LabView (National Instruments, Austin, TX), the designed paths are sent to the bioprinting system. The bioprinter builds structures by depositing bioinks following the instructions sent by the software (Fig. 2, step 5). ...
Given its potential for high-resolution, customizable, and waste-free fabrication of medical devices and in vitro biological models, 3-dimensional (3D) bioprinting has broad utility within the biomaterials field. Indeed, 3D bioprinting has to date been successfully used for the development of drug delivery systems, the recapitulation of hard biological tissues, and the fabrication of cellularized organ and tissue-mimics, among other applications. In this study, we highlight convergent efforts within engineering, cell biology, soft matter, and chemistry in an overview of the 3D bioprinting field, and we then conclude our work with outlooks toward the application of 3D bioprinting for ocular research in vitro and in vivo.
... Figura 1 -Biofabricação (adaptado de Dernowsek et al., 2017a) Este trabalho propõe a criação de modelos in silico dos processos da biofabricação abordando a modelagem e a simulação computacional, a fim de possuir um controle maior dos agentes envolvidos, como por exemplo, tipos celulares, proteínas e fatores de transcrição (Dernowsek et al., 2017c). Ao possibilitar o domínio de tais parâmetros, tornase viável o estudo das influências dos mesmos em cada parte do processo biológico. ...
Este trabalho propõe o desenvolvimento de um modelo virtual preditivo para os processos da biofabricação e bioimpressão, por meio da integração das áreas biológica, exata e computacional. O uso de biomodelos preditivos na bioimpressão aumentarão a compreensão dos sistemas vivos, relacionando o comportamento básico das moléculas a complexas interações biomecânicas existentes nos tecidos e órgãos. Esses conhecimentos integrados têm o potencial de padronizar procedimentos, transformando a biofabricação em um processo reprodutível e escalável. Como parte deste objetivo, estuda-se a modelagem e funcionamento da osteogênese-formação de matriz óssea-por meio de simulações computacionais que envolvem as principais biomoléculas estimuladoras do processo. Palavras chave: biofabricacao, simulacao, in silico, modelagem, osteogenese 1. INTRODUÇÃO A integração de processos físicos, químicos, biológicos e de engenharia com a finalidade de controlar e direcionar o comportamento de células é chamada de engenharia tecidual. Ela, unida à medicina regenerativa, deram origem à biofabricação-o desenvolvimento de produtos biológicos a partir de materiais vivos e seus produtos (Groll et al., 2016). Uma das estratégias utilizadas na biofabricação é a bioimpressão-a utilização de técnicas de manufatura aditiva que utiliza materiais biológicos como matéria prima. As aplicações da bioimpressão vão desde a utilização de microtecidos impressas em testes de fármacos e cosméticos até, futuramente, o transplante de tecidos e órgãos impressos. O aumento da expectativa de vida da população e o crescimento da quantidade de ocorrências de doenças ósseas tornam cada vez mais necessários os estudos de métodos de prevenção e reconstruções ósseas. A biofabricação vem como alternativa promissora às estratégias atuais que utilizam enxertos, ao envolver biomateriais, células e biomarcadores nos processos de reparo e formação da matriz óssea (Dernowsek et al., 2017; Mattioli-Belmonte et. al., 2017). A bioimpressão faz-se interessante devido a sua capacidade de acurácia, automação, reprodutibilidade e customização das estruturas biofabricadas. Vale lembrar, porém, que o maior desafio atualmente é dominar as interações a nível molecular, celular e tecidual que levam aos comportamentos biológicos observados nos sistemas vivos, para posteriormente focar na reprodutibilidade de um órgão completo. Figura 1-Biofabricação (adaptado de Dernowsek et al., 2017a) Este trabalho propõe a criação de modelos in silico dos processos da biofabricação abordando a modelagem e a simulação computacional, a fim de possuir um controle maior dos agentes envolvidos, como por exemplo, tipos celulares, proteínas e fatores de transcrição (Dernowsek et al., 2017c). Ao possibilitar o domínio de tais parâmetros, torna-se viável o estudo das influências dos mesmos em cada parte do processo biológico. Especificamente, será apresentada uma simulação do processo de osteogênese que poderá ser utilizada como modelo preditivo, por exemplo, como modelo de produção de tecido ósseo a fim de restaurar estruturas e funções danificadas por traumas na área da biofabricação. 2. OSTEOGENESE A diferenciação é o processo em que células especializam-se para que possam realizar uma função específica (Bianco et al., 2001). Isso acarreta não somente uma mudança funcional, como também estrutural para a célula. O código
... Knowledge, biomechanical data, computer-aided design (CAD) and computational models are required. The biological phenomena present in bioengineering problems are a combination of multiscale interrelated components such as molecules, regulatory networks, cells, tissues, whole organism, biomechanical properties, among others [1]. ...
... Tissue engineering and the bioengineering assist in the modeling of biological systems, initially studying the behavior of a basic living unit like tissue spheroids and then moving into its relationship with others neighbors spheroids to form a complex tissue. A range of multiscale strategies was employed to develop a BioCAE for bioengineering studies preventing a significant amount of trial-and-error experiments in laboratories [1]. ...
Abstract Computer Simulation for biological and bioengineering purposes is being referred today also as In silico as a first approach for the In Vitro and In Vivo expensive and time-consuming tests. It is a necessary and fast-growing field of interdisciplinary knowledge to fulfill today's and future demands, ranging from bioengineering modeling and simulation of mechanical devices to the more complex and uncertain field of biofabrication of human tissues and organs towards we call Medicine 4.0. In order to establish models for the phenomena studied, not only the boundary conditions and mathematical representation of such chemical, biological, biochemical and physical phenomena has to be implemented, but the computational approach to obtain representative models and relevant results as a feasible task. Such models can bring solutions to one level of complexity according to the specific problem to be solved. On the other hand, it is practically impossible to establish more complex models for high-level solutions as the ones necessary for complete organisms and organs simulations, for example, due to its complex integration in many levels from molecular to the high-level behavior of such organisms and organs. Therefore, like engineering approach, it is mandatory for future solutions the integration of multiscale models from molecular to whole organism levels. This paper sheds some light on this subject not only proposing a preliminary framework as a basis for multiscale simulation but also showing, using case studies, the complexity and necessary simplification for some of those levels involved in a possible framework from bioengineering to biological multiscale simulations. The case studies presented in this paper are only a small set of models illustrating the challenges and needs for a complete integrated framework. They were developed initially as a specific demand in a stand-alone approach at 3D Technologies Research Group in the Renato Archer Information Technology Center. © Author(s), 2017. Published by Rational Publication. This work is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc/4.0/ or send a letter to Creative Commons,
Piezoelectric inkjet 3D bioprinting technology is a viable technique for ophthalmological applications. It provides versatility, high sensibility and accuracy, required in ophthalmological procedures. A process flow for biofabrication was described in detail and validated, using piezoelectric inkjet technology, for ophthalmological applications, in vitro and in situ, based on complex images. Ophthalmological problems were documented by diagnostic examinations and were fed to the flow as complex images. The Concept Mapping methodology and the Conceptual Design approach were utilized to elaborate the 3D bioprinting process flow. It was developed a bioink with corneal epithelial cells. To simulate an in situ bioprinting process, eyes of pigs were selected as the substrate to print the cells. Print scripts used the digitally treated images. In order to print on predefined locations, alignment devices and sample holders were built. The proposed process flow has shown to be a potential tool for the biofabrication of ophthalmological solutions.
Living tissue consists primarily of cells and extracellular matrix. Cells perform functions, communicate, respire and remodel extracellular matrix. Likewise, diffusive chemical conditions and extracellular matrix exhibit their own effects on cellular and intracellular processes, depending on the consistency of the matrix and phenotype of the cell. These interactions produce the emergent phenomena of tissue function, repair and morphology. Computational modeling seeks to quantify these processes for the purposes of fundamental study and predictive capability in various applications, including wound healing, tumor vascularization and biofabrication of living tissue. Hybrid kinetic Monte Carlo models are well known to be capable of predicting observed behaviors like cell sorting and spheroid fusion due to differential adhesion and energy minimization. However, no hybrid model sufficiently provides a formal treatment of full cell, chemical and matrix interactivity in a dynamic environment, including heterogeneous matrix conditions, advecting materials, and intracellular processes. In this work, hybrid kinetic Monte Carlo models are developed to describe full interactivity of cells, soluble signals and insoluble signals in a complex, dynamic microenvironment at the cellular level. Modeling of intracellular chemical dynamics and effects on the cellular state is developed as stochastic processes, and cell perform metabolic and matrix remodeling activities. Computational models of select in vivo and in vitro phenomena are developed and simulated, showing the ability to simulate new phenomena concerning cell viability, growth dynamics, highly heterogeneous cellular distributions, and complex tissue structures resulting from phenomena like intercellular signaling, matrix remodeling, and cell polarity.
The biofabrication of engineered tissues is an essential area to reconstruct tissues. Until now, to the best of our knowledge, it has not been possible to mimic the biological and biochemical properties. New approaches to developing a new tissue become an attractive target for bioprinting, which is emerging as an essential strategy to recreate the histoarchitecture and the relationship between cells, matrix, and microenvironment. Simulation in a microscale study is a crucial factor to understand specifics physical phenomena and how they affect biological tissue formation. The objective of this paper is to analyze the behavior of the stress on the hierarchical layers of the cartilage using finite element method. The interaction of the collagen fibers with the chondrocyte was observed through the contact regions of the Minimum Principal Stress (compression) analysis accompanied by deformation results. The boundary conditions were applied to a standard 50 μm edge cube with a perpendicular pressure of 4.5*10-5 MPa. The results are promising for future simulations of more detailed models with bias in vivo and in vitro. DOI: https:/doi.org/10.24243/JMEB/3.5.199 2019. Published by Rational Publication.
A medicina 4.0, fazendo uma alusão à indústria 4.0, engloba fortemente a biofabricação de tecidos e órgãos, baseando-se numa miríade de emergentes tecnologias, especialmente no campo da medicina regenerativa, tratamento e diagnósticos personalizados e na descoberta de novos fármacos. Assim sendo, o avanço da impressão 3D, bioimpressão, microfluídica, nanotecnologia, inteligência artificial, imageamento, modelagem e simulação computacional, estarão entre as áreas de maior impacto na saúde e, consequentemente, de intenso crescimento econômico.
