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:
·
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 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 3-dimensional
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/B-Biotissue.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
By
Christine Brown and Jessica Laclair