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Semple et al. (2005): Review: In Vitro, in Vivo, in Silico: Computational Systems in Tissue Engineering and Regenerative Medicine
As the title says, this is about the usage of computers in tissue engineering. Regarding the importance of these techniques for tissue engineering, the authors write:
In tissue engineering the ability to apply accurate modelling and new cell simulation techniques can provide vital information and answer key questions regarding cell, tissue, and ultimately organ behavior.
About the role of computers they state that "in silico methods can supplement and extend the current empirical techniques of tissue engineering and regenerative medicine" and that:
Computers routinely monitor the course of experimental procedures; gather, smooth, and record data and signals; and provide an effective medium though which data can be analyzed, visualized, communicated, and disseminated widely by means of databases connected to electronic networks. They also place in the hands of the researcher tools for statistical and mathematical analysis, by which specific hypotheses can be evaluated on the basis of assembled arrays (often vast) of data.
What are the grand challenge areas in this context? The authors write:
One of these grand challenge areas is, undoubtedly, the mustering of digital procedures that will somehow monitor, collate, and otherwise manage the explosion of online databases across genomics, proteomics, organisms, cell lines, and tissue projects, allowing researchers to identify and extract data essential to targeted needs. A related challenge is the need for data-mining procedures able to “drill down” into the layers of catalogued information and extract key discoveries otherwise buried among terabytes of compiled results. The problems and current advances in the emerging discipline of tissue-engineering data mining have been surveyed extensively and need not be discussed further here. We turn instead to a third grand challenge: the use of computers as in silico bioreactors that (at least partially) replace laboratory bioreaction technology as the medium in which to engineer functioning tissues; this is one of the key areas where the future of “tissue-engineering in silico” resides.
The paper further states that "the long-term goals of regenerative medicine can usefully be organized around two concepts: that of tissue equivalence, and that of tissue isomorphism". Regarding the former concept:
[A]s a praxis of equivalence design, regenerative medicine seeks to fabricate tissue replacements that encapsulate essential function economically, usually by minimizing the number of functional equivalences that must be emulated.
Concerning the latter concept, the authors suggest that "the mathematics of morphogenesis is a waypoint to better implants".
Acccording to the authors, "three periods of mathematical and computational innovation" can be distinguished:
[A]n early period (1930–1970), in which attention focused on highly idealized models meant to identify physical and biochemical forces essential to understanding morphogenesis in mathematical terms; a pregenome period (1970–1990), in which early molecular cell biology was harnessed to mathematical cell biology and produced models of improved realism; and the current postgenome period (1990–), in which a rigorously molecular developmental biology is enabling detailed models set in silico on fast, high-capacity, inexpensive computers.
In the first period, researchers initially worked with Rashevsky models, which "considered only abstract patterns of chemical reaction acting within and across the plasma membranes of simple spherical cells". Later "Turing’s reaction–diffusion equations would emerge [...] as the near-universal mathematical language for describing the biochemistry of spatiotemporal pattern formation in cells and developing organisms".
In the second period, there were two different approaches:
One approach was to enlarge Rashevsky’s focus and treat tissues as populations of discrete interacting cells, and to calculate the morphogenetic outcomes of these interactions. A second was to follow the early lead of Keller and Segel and treat developing tissues not as assemblies of anatomically discrete cells, but as continuous deformable media amenable to treatment by the equations of continuum mechanics. Both approaches made influential advances during this period.
In the third period, "numerous competing pieces of computer software" emerged, "designed to allow users without extensive mathematical background to apply ordinary differential equations and stochastic simulation to model cell chemistry and transport reactions (e.g., KINSIM, GEPASI, FITSIM, MEG, SCAMP, MIST, ECell, the Virtual Cell, and MetaModel)".
The authors forecast:
In the near future computational methods will allow for the custom development/fabrication of scaffolds to the specification of the recipient. Computational tissue reactors can test construct prototypes in silico. In silico tissue reactors and other computational methods have the greatest potential in future to replace aspects of in vitro methodology.
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