MM™

TISSUE ENGINEERING:
HALLMARK OF MODERN MEDICINE
BBS1224 | CELL&TISSUE CULTURE
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What is Tissue Engineering?

Tissue engineering is an emerging multidisciplinary field involving biology, medicine, and engineering that is likely to revolutionize the

INTRODUCTION
ways we improve the health and quality of life for millions of people worldwide by restoring, maintaining, or enhancing tissue and organ
function. In other words, tissue engineering is the development of artificial tissue and organ systems.
The term regenerative medicine is often used synonymously with tissue engineering, although those involved in regenerative medicine
place more emphasis on the use of stem cells to produce tissues.

Animal Tissue Culture ↔ Tissue Engineering

The term “tissue engineering” only appeared in 1987 during
United States’ National Science Foundation meeting, which they
define as “a new inter-disciplinary initiative which has the goal of
growing tissues or organs directly from a single cell taken from an
individual”. Since then, this new emerging scientific spectrum
become a focus of research institution across the globe,
particularly at USA and Europe. UKM’s Tissue Engineering and
Human Genetics Research Team is a pioneer and leader in this
area in Malaysia.

Animal tissue culture allows for the advancement of tissue

engineering. Two main strategies in tissue engineering are:
• grow cells in-vitro on transplant.
• implant matrix and regenerate host cells.
Why it is gaining interest nowdays?
Cost to repair damaged tissues allows to more than a trillion
annually, globally. In USA alone, liver transplant and aftercare cost
over a billion USD. More than 10,000 people have died during the
past five years while waiting for an organ transplant.

Tissue engineering potentially offers dramatic improvements in

Cells and tissues commonly involved in tissue engineering,
in clockwise: cornea, skin, various human genes,
biomaterial, bone, cartilage.
medical care for hundreds of thousands of patients annually, and
equally dramatic reductions in medical costs; due to the
availability of less expensive treatments and minimizing time
waiting for compatible organ donor, since “engineered"
replacement organs became reality.
 Typical Processes Scaffold
Cells are often implanted or 'seeded' into an artificial structure

METHODS AND TECHNIQUES

capable of supporting three-dimensional tissue formation called
scaffold. Functions of scaffold are as follows:
• allow cell attachment and migration
• deliver and retain cell and biochemical factors
• enable diffusion of vital cell nutrients and expressed products

Scaffold must meet some requirement:

• high porosity
• adequate pore size
• biodegradability (after the new tissue built its own
mechanical support)

Natural scaffold are proteic materials, such as collagen or fibrin,

and polysaccharidic materials, like chitosan or glycosaminoglycans
(GAGs). A commonly used synthetic material is PLA - polylactic
acid. As cell produce extracellular matrix and proliferate, synthetic
polymer scaffold degrades.

Growth Factor

1. Remove cells1; The choice of growth factors depends solely on the types of
2. Expand number in culture; culture. Rich medium formulations like 199 and simpler media
3. Seed onto an appropriate scaffold2 with suitable growth factors3 like MEM are popular. Other combinations might include serum,
and cytokines4; additives like insulin, transferrin, ethanolamine and selenium. In
4. Place into culture5; order to reduce cell aggregation, Ca2+ and Mg2+ ions have to be
5. Re-implant engineered tissue repair damaged site. omitted from the medium, or alternatively low levels of trypsin
may be added to the medium. Ideal pH of the medium should
1
From fluid tissues such as blood, cells are extracted by bulk methods,
between 7.0 to 7.4.
usually centrifugation. From solid tissues usually the tissue is minced,
and then digested with the enzymes trypsin or collagenase to remove the Bioreactor
extracellular matrix that holds the cells.
2
Artificial structure capable of supporting three-dimensional tissue formation. More Custom-made devices called bioreactors allow for precise and
information at right. continuous control of culture conditions and also allow for
3
Protein capable of stimulating cellular proliferation and cellular differentiation. introduction of different stimuli to tissue cultures.
4
Group of proteins and peptides that are used in organisms as signalling compounds
5
Sometime in bioreactor. More information at right.
Current Uses Jackpot : Artificial and Synthetic Blood

• skin tissue replacement for ulcerations. Dozens of biotech companies from around the globe was involved

APPLICATION AND PROSPECTS

• scaffold that allows the slow release of an anticancer agent to
combat a form of brain cancer.
• artificial pancreas that help diabetes patient.
• artificial bladder.
• lab-grown cartilage used to repair knee cartilage.
in search of artificial and synthetic blood because of its huge
economic potential. Blood supply is problematic:
• viral infection risk: HIV, Hepatitis
• storage conditions
• supply shortages

From Laboratory to Commercial Venture

Biopure Inc. Hemopure® is the first artificial blood that has been
approved for clinical use - in South Africa (2001). It is purified
BioTissue Technologies Inc. have several products commercially
cows hemoglobin. It has a 2 day half life. Side effect is an increase
produced, including skin repair, oral connective tissue, and
in blood pressure
cartilage.

BD Bioscience specialize in artificial bones.
BioHeart Inc. specialize in regeneration of heart cells in vitro.
• inject heart cells into patient to repair damaged tissue
• in third stage human clinical trials in Europe
Polyheme® is hemoglobin extracted from expired blood. The
product is supplied as a dried powder which is reconstituted and
has longer shelf life.
Oxygent® is synthetic blood which uses perfluoro-chemicals as
the oxygen carrier. Surfactants, salts and water are added

Prospects and Challenges

Although future of tissue engineering is very promising, finding
effective scaffold is still a major issue in the creation of more
complex, large-scale structures. Some say fabrication of
nanofibrous materials can provide the answer. At the other side,
the question of whether and how to control the creation and use
of technology raises ethical issues of great concern to society.

Conclusion

As a foundation of tissue engineering, animal cell and tissue culture provides extensive probabilities for human being to improve health
quality, today and tomorrow. But, there is still much to be done and learned, scientifically and economically, to ensure that the benefits of
this technology will truly help everyone and without any notable, harmful side-effects.