CELL & TISSUE
E N G I N E E R I N G
Jun OUYANG MD
Southern Medical University
Joint Research Center of Biomedical Engineering and Material
• What if lost limbs or organs could be
regenerated?
• What if drug development and chemical
testing were more efficient and less costly?
• Can deadly biological and/or chemical
agents be rapidly identified?
• Are there ways to reduce our reliance on
animal testing?
What’s Tissue Engineering?
– TE is an emerging multidisciplinary field
involving biology, medicine, and engineering
that is likely to revolutionize the ways we
improve the health and quality of life for
millions of people worldwide by restoring,
maintaining, or enhancing tissue and organ
function. (NIH)
• Tissue engineering research includes:
– biomaterials,
– cells,
– biomolecules,
– engineering design aspects,
– biomechanics,
– informatics to support tissue engineering
– stem cell research.
• A brief history of TE
– First put forward in 1985
– Pre-clinical research during 1990s
– TEMP (Tissue Engineering Medical Product)
in late 1990s
• A brief history of TE
– The Multi-Agency Tissue Engineering
Science (MATES) Interagency Working
Group (IWG), 2000
The Multi-Agency Tissue Engineering Science
(MATES) Interagency Working Group (IWG)
Department of Agriculture (USDA)
Department of Commerce
National Institute of Standards and Technology (NIST)
Department of Defense (DoD)
Defense Advanced Research Projects Agency (DARPA)
Centers for Medicare & Medicaid Services (CMS)
Department of Health and Human Services (HHS)
Food and Drug Administration (FDA)
National Institutes of Health (NIH)
Department of Energy (DOE)
National Aeronautics and Space Administration (NASA)
National Science Foundation (NSF)
Naval Research Laboratory (NSF)
Veterans Administration (VA)
• A brief history of TE
– TERMIS (Tissue Engineering & Regenerative
Medicine International Society,2005)
Advancing Tissue Science
And Engineering
• A Multi-agency Strategic
Plan ( 2007 )
• From earliest diagnostic
testing To the advanced
stages of therapy.
Four overarching goals
• Understanding and controlling the cellular
response;
• Formulating biomaterial scaffolds and the
tissue matrix environment;
• Developing enabling tools;
• Promoting scale-up, translation and
commercialization;
Understanding and Controlling
The Cellular Response
• Tissue-Engineered Disease Models:
• 3-D tissue models was established to study
the growth of tumors in tissue beds and for
use in drug screening.
Understanding and Controlling
The Cellular Response
• Engineered Tissues Provide
Alternatives to Animal
Testing.
• Currently, engineered skin
products are the most widely
used.
Stem Cells for Tissue Science
and Engineering
• Various tissues of the
adult body have been
used as a source of
stem cells ( e.g., fat,
muscle, skin).
• To control cell
phenotype and direct
tissue formation is the
ultimate goal.
Formulating biomaterial scaffolds
and the tissue matrix environment
• Guide the growth, differentiation and
organization of cells;
• Give support, strength and for to tissue
and organs.
Formulating biomaterial scaffolds
and the tissue matrix environment
• Hight molecular compound
– Polylactic acid (PLA),
– Polyglycolic acid (PGA),
– Polycaprolactone (PCL)
Formulating biomaterial scaffolds
and the tissue matrix environment
• Matrix:
collagen, elastin, proteoglycans and wide
variety of other proteins and signaling
molecules.
Facing difficulties
• Understanding and quantifying the
relationship between biomaterial scaffolding
characteristics and physiological responses
remain among the most pressing materials
challenges.
Developing enabling tools
• The development of tissues is the result of
molecular and supramolecular interactions that
occur on a continuum of time and spatial scales
in response to the many chemical and physical
parameters within cells, between cells and within
organisms.
• Achieving sufficient insight into these
complicated relationships needs knowledge and
computational model.
Biomarkers, High-throughput/ Content
Assays and Instrumentation
• Assessing the
physiological state or
condition of a cell or
tissue
• Rapid screening of novel
materials as candidates
for scaffolding.
Imaging Technologies
• Imaging challenges include
development, optimization, and
integration of technologies at
the many levels-from molecular
to tissue to whole body.
Computational Modeling and
Bioinformatics
• Understanding the intracellular machinery,
will require assimilating vast amounts of
data into computational models;
• Such models will be critical for allowing
prediction and subsequent testing of the
large number of parameters that influence
cells, tissues, and organs.
Fabrication Technologies
• Rapid prototyping (RP)
technology was used
in TE field;
• Majority of effort
should on deposit
cells in the layers
during the fabrication
process.
Bioreactors
• Producing 3D tissues
in vitro requires;
• NEED: Design
devices that can
support self-assembly
of multiple cell types
into complex tissue
structures.
Tissue Preservation and Storage
methodologies
• It is very important for • Wood frogs
basic research,
device development
and clinical
applications.
• Preservation
techniques are far
from perfect.
Promoting scale-up, translation and
commercialization
• Much work to be done on the technical
side in translating lab-scale fabrication
techniques into large-scale production of
high-quality products that meet GMP
standards.
• TEMPs is “combination products” and
need new standards and rules.
TEMPs Industrialization
Tremendous market potential
z Organ replacement >65 ys, 1/5 (USA)
z 8% medical spending，$350 Billion per year
z Operation $8 Million/year worldwide
z 40-90 million days/year in hospital
z Bringing a new drug estimated $800 Million over 12 years
Enterprise of TEMPs
• In 2002, 89 biotechnology organizations
were involved in TE R&D worldwide.
• Theragnostices TEMP is anticipated to be
$3.7 Billion by 2009.
TEMP Classification
¾ Structure and function
Simple (Cartilage,tendon,bone,skin et al.)
Complex (Liver、Kidney et al)
Cell transplantation and capsule (Pancreas)
TEMP Classification
¾ Composition
Cells only( Epicel, Carticel )
Cell and biomaterial( Apligraf )
Biomaterial only( Alloderm )
Total spending
$700
Annul Spennding,$millions
$610
$600
$500 $435
$400
$300 $246
$200
$100
$0
1995 1998 2000
—— Lysaght, Tis. Eng. 7,2001
Enterprise of TEMPs
Structural Metabolic Cellular
Skin,bone, heart Bioartificial Cell trans-
Examples
valves organs plantation
Employee 1980(60%) 570(11%) 890(27%)
R&D spending $3.63亿 $0.68亿 $1.74亿
—— Lysaght, Tis. Eng. 7,2001
Comparison of USA & European
USA European
Funding Sources Industry Government
Research focus Application Basic
Cellular sources auto/allograft autograft
Biomaterials new material modification
Bioreactor On top
Standards On top
WTEC, Jan, 2002
Thank you fro your attention!