Chemical Engineering and Tissue Engineering
The combination of Chemical Engineering and Biotechnology provides enormous
opportunities for research which can lead to significant improvement of life quality and
wealth creation. The manufacture of therapeutic proteins, hormones and materials for
gene therapy etc needs specific chemical engineering skills, for example in bioreactor
design, bioproduct separation and purification, and product formulation. Tissue
Engineering aims to develop biological substitutes to solve the problem of organ and
tissue deficiencies and provide the next generation of medical implants. Tissue
engineering, by its nature, needs a multi-disciplinary approach and requires expertise in
engineering, biomaterials, life sciences (cell and molecular biology, immunology), and
clinical practice. Chemical engineering plays a key role in any engineered tissue
development by solving problems in bioreactor design and operation, scale-up, and
preservation of the engineered tissue products.
A chief part of ATS' engineering is building enclosed systems (bioreactors) to grow and ship tissue without degradation. 1
Examples of a Chemical Engineers’ involvement include:
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Downstream separation and purification of biopharmaceuticals such as
antibodies and other therapeutic proteins and application of membrane
processes. Other separation techniques including chromatography and
precipitation.
Studying virus inactivation kinetics, heat transfer and residence time
distribution, modeling and simulating fluid flow and mixing, and the
experimental validation of virus inactivation.
Design and operation aspects of new types of bioreactors, particularly
addressing mass transfer and mechanical signaling.
Development of membrane systems capable of fractionating the complex
protein mixtures encountered in many biotechnological, food processing, and
biomedical applications. This is difficult due to concentration polarization and
protein-protein interaction. One approach used is gas sparging to overcome
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concentration polarization, and alter the physiochemical conditions (i.e. pH
and ion strength) to adjust protein-protein interaction.2
Mass transport and materials synthesis
Lymphatic transport, tissue fluid balance and transport, mechanotransduction.
Bioreactor for large-scale bioproduct manufacturing.
UPSTREAM PROCESSING
Upstream processing encompasses any technology that leads to the synthesis of a product
as well as the fundamental science and engineering needed to understand product
formation. Specific areas of opportunity include biocatalysis, metabolic engineering,
biomass conversion, bioreactor design and cell culturing techniques, and transgenic
animals.
Bioreactor Design and Cell Culturing Techniques
If the great variety of potentially commercial bioprocesses are to be developed and
applied, then bioreactors must be designed in which the environment can be controlled
precisely to maximize process efficiency. The design of a bioreactor requires a basic
understanding of both chemical reactor design and cell biology. First, designers must
understand the effects of reaction rates and stoichiometry, mass transfer, heat transfer,
and turbulence and mixing on product distribution, reactor productivity and size, and
operational characteristics. These phenomena need to be expressed in accurate but
tractable models that can be used for design and optimization calculations. In order to
develop effective cell culturing techniques, designers also must have basic knowledge of
cellular functions and protein chemistry. They should understand the molecular, genetic,
and metabolic processes involved in the growth of cells and the expression of cellular
products; and structure/function relationships in the use of proteins for biochemical
conversions.
DOWNSTREAM PROCESSING
Downstream processing includes the cost-effective separation and purification of
bioproducts, as well as biorefining. Often, downstream processing is the most expensive
phase of producing a substance of biological origin, especially for products with stringent
regulatory requirements. A key reason for this high cost is the complex and dilute nature
of the aqueous solutions in which bioproducts generally are produced; an inverse
relationship has been demonstrated between the price of biological products and the
strength of the concentrations from which they must be isolated. The high cost of
downstream processing means there is significant potential for savings from improved
processes. For regulated bioproducts, such as pharmaceuticals, removal of trace
impurities is the expensive step in the purification.
Separation and Purification
The separation and purification of materials produced in a bioreactor is a critical part of a
manufacturing operation. The biological products involved range from high-value-added
substances used as pharmaceutical agents (e.g., insulin) to lower-cost products including
commodity chemicals (e.g., ethanol). High-value bioproducts are usually fragile
molecules, such as proteins or peptides that require highly specialized and mild
processing conditions and may need to be separated from a complex mixture of
molecules, including cell debris. This combination of factors makes separation difficult.
At present, most separation schemes are scaled-up laboratory procedures; research is
needed to improve their performance.
Biological processes one day may offer economical alternatives to current,
petrochemically based methods for manufacturing organic acids and alcohols. However,
before these bioprocesses can become commercially viable, nontraditional, lower-cost
separation methods need to be developed. Research is under way to develop extracting
solvents, resins (separation media), and sorbents that are more selective and have a higher
capacity than do current materials. Reversible extraction systems are needed that respond
to changes in temperature, pressure, or acidity. Combinations of conventional separation
methods and biological methods are being explored to reduce product inhibition, which
often occurs in fermentations that produce alcohols and solvents. In addition,
mathematical models of separation steps need to be developed to help reconcile
regulatory requirements with basic process conditions during early stages of process
development, and to meet the demands of a competitive business environment. Modeling
enables scale-up considerations to be estimated very quickly, a capability needed in order
to commercialize a bioprocess in an industry where being the "first to market" is a critical
element of success.3
Rotating tissue culture vessels, which simulate some aspects of microgravity, allow human cells to grow and assemble into 3dimensional tissues. This new class of culture vessel has enabled the growth of normal and cancerous human tissues outside the body
and is a tool for gaining important information with applications in medicine and the biology. The figure shows a human cell grown in
a rotating tissue culture vessel.
In conclusion, tissue engineers are an eclectic group which includes chemical engineers,
chemists, cell biologists, and surgeons. The field draws upon the chemical engineer's
expert knowledge of fluid dynamics, mass transport, process modeling, materials design,
and chemistry. Chemical engineers are designing biocompatible casings for cell
transplants, polymer composites for patching wounds, scaffolds that guide and encourage
cells to form tissue, bioreactors for large-scale production of therapeutic cells, and
experimental and mathematical models to predict cell behavior. However, there are still
many challenges that need to be overcome. Some include missing information on how to
develop universal donor cells that could be given to any recipient, how to stimulate
regeneration of complex multicellular structures in vivo, or how an organ directs the
function of its cells.4 Therefore, success in Tissue Engineering is going to require
interdisciplinary participation and determination.
References:
1. http://www.memagazine.org/backissues/february99/features/skin/skin.html
2. Taken from http://www.eng.ox.ac.uk/World/Research/Summary/BBiotissue.html
3. Taken from http://www.nal.usda.gov/bic/bio21/bioproc.html
4. Taken from http://www.eng.nsf.gov/engnews/94-96News/95Spring/1995.htm
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By Christine Brown and Jessica Laclair