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

 

 

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By Christine Brown and Jessica Laclair