IMI Interdisciplinary Mathematics InstituteCollege of Arts and Sciences

Why mathematical modeling, computational biology and computer simulation is essential for proper development of organ printing technology

  • Nov. 11, 2009
  • 2:30 p.m.
  • Sumwalt 102


Concept of tissue fluidity was introduced in developmental biology by Malcolm Steinberg as integral part of his Differential Adhesion Hypothesis (DAH) almost 50 years ago. DAH have been experimentally proven in silico, in vitro and in vivo. Embryonic tissue and tissue spheroids (cell aggregates) behavior can be approximated as behavior of visco-elastic fluid. There are already several well established technologies for measuring material properties of embryonic microtissue (cell aggregates or tissue spheroids) in vitro using tensiometers or aspiration device. Atomic force microscope was used for study embryonic tissue biomechanics in situ and in vivo. Recent reemerged interest to DAH is partly driven by fast emerging area of mechanobiology or increased recognition of role of mechanical factors in mechanisms of embryonic morphogenesis. Exploring of tissue fluidity in rapidly evolving organ printing technology is another possible reason for growing interest to classic work of Malcolm Steinberg. Mathematical modeling and computer simulation is a powerful tool for study tissue fluidity. It is interesting that classic Glazier and Graner paper about modeling of cell sorting in cell aggregates is more cited then original experimental papers on actual measurement of tissue surface tension. Recent progress in computer simulation or computer-aided visualization of mathematical models reduce interdisciplinary barriers and makes interaction between experimental developmental biologists from one side and mathematicians, biophysicists and computer scientists on another side much more feasible. Tissue fusion driven by surface tension forces is a ubiquitous phenomenon during embryonic development and it is also a fundamental principle of emerging organ printing technology which could be defined as a layer by layer computer-aided automated additive robotic biofabrication of functional human organs from self-assembling tissue spheroids. Understanding and controlling tissue fusion and fluidity is essential for successful development of organ printing technology. In essence, organ printing technology is an exploration or practical application of concept of tissue fluidity. Designing of "blueprint" for bioprinted human organs is not possible without predictive mathematical modeling and computer simulation of tissue fusion, compaction and remodeling. Initial results demonstrating a feasibility of automated robotic bioprinting of branched segments of intraorgan vascular tree using self-assembling vascular tissue spheroids as well as novel in vitro high throughput quantitative assays for screening tissue maturation factors will be presented. Morphogenesis is one of complex biological process and using only molecular biology and molecular genetics reductionist approach does not guarantee a complete understanding of complexity of embryonic development. It is becoming increasingly obvious that the effective implementation of holistic trans-hierarchical systemic and synthetic approaches in developmental biology such as Systems Biology is impossible without effective employing computational biology. Mechanobiological approach also reflects increasing attention to study of physical mechanisms of morphogenesis based on tracing and visualization of cell and tissue movements, direct and indirect measuring of physical forces and material properties of living tissues. Thus, it is safe to predict that research on "Quantitative Tissue Biology" and "Virtual Tissues" will be integral parts of XXI century Developmental Biology, Tissue Engineering and Regenerative Medicine.

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