Download Tissue Engineering Skin: A Paradigm Shift in Wound

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Tissue Engineering Skin:
A Paradigm Shift in
Wound Care
C. Mason
Advanced Centre for Biochemical Engineering, University College London, UK
Improving on the bandage
It is remarkable that an organ with a
surface area of approximately 2 m2,
which performs a multitude of essential functions for everyday survival,
requires so little medical maintenance
for it to last a lifetime. However,
when skin does fail, for example,
with third-degree burns or chronic
leg ulcers, the result is potentially
catastrophic for the patient. Although
bandaging has an important role, the
results are far from ideal with slow (if
ever) wound healing and scarring.
As published
in the
December
2005 issue
of Medical
Device
Technology.
Skin graft options
The current “gold standard” for treating large skin losses is an autologous
(from the patient) skin graft. However,
this requires a second operation site,
which may heal extremely slowly in
older patients, and in severely burnt
patients there are frequently inadequate
amounts of undamaged skin to keep
the patient alive, let alone to harvest. A
proven alternative is tissue-engineered
skin. To date, several hundred thousand
patients have benefited from being
treated with a living skin substitute.
For example, the leading company,
Organogenesis (Canton, Massachusetts,
USA, www.organogenesis.com) currently produces enough skin to treat
december 2005 ❘ medical device technology
more than 8000 patients per quarter
with its flagship product, Apligraf.
With a reimbursement rate of approximately US$1200 for a 7-cm diameter
piece, the therapy at first glance looks
extremely expensive compared with
conventional bandages. But when
all the other factors are taken into
account, for example, a far superior
rate of healing and associated benefits
such as reduced amputation rates
and improved quality of life, there is
no argument about which approach
is really financially superior. Other
serious contenders for treatments in
the hard-to-heal ulcer category such
as venous leg ulcers and diabetic foot
ulcers are Dermagraft (originally
from Advanced Tissue Science, La Jolla,
California, USA, acquired by Smith
& Nephew in 2002 and now up for
sale again, www.smith-nephew.com);
ICX-PRO (Intercytex in Cambridge,
UK, www.intercytex.com), which
is currently about to enter phase
three trials; and OrCel (Ortec,
New York, New York, USA,
www.ortecinternational.com).
Burn treatments
Apart from ulcers, the other important
skin market is burns. Large burns
require urgent grafting to control
Image: Digital Vision
Tissue-engineered skin for the treatment of
burns and ulcers is a clinical success, but making
it commercially viable is more problematic. This
article examines the industry, its techniques and
suggests the way forward.
pain, to reduce scarring and, most
importantly, to reduce fluid losses
and prevent infections, which are the
leading causes of death in severely
burnt patients. The major player in
this arena is Genzyme Biosurgery
(Boston, Massachusetts, USA,
www.genzymebiosurgery.com),
which has grown more than 140000
pieces of Epicel skin that is used to
treat patients with severe burns covering greater than 30% of their body.
The average Epicel patient requires
250–500 pieces of the 50-cm2 skin
substitute. The leading company
in the United Kingdom offering a
product for this application is Celltran
(Sheffield, UK, www.celltran.co.uk)
with its Myskin.
The skin market
It is generally agreed that there is a
big market for skin; for example, in
the United States each year more than
half a million patients are treated for
venous ulcers and tens of thousands
are admitted to hospitals with severe
burns. The market is even bigger if
tissue-engineered cosmetic products
(“aesthetic medicine”) are included
such as the Isolagen Process (Isolagen,
Houston, Texas, USA, www.isolagen.
com). However, the methods of
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then formed into sheets, packed and
shipped back for surgical implantation; this is a logistics nightmare but
one that Genzyme Biosurgery has
developed to the highest standards as
a humanitarian device.
Commercial viability
With Genzyme Biosurgery producing
Epicel as a not-for-profit product
because of its complexity and, therefore, cost of manufacture, and Smith
& Nephew exiting its Dermagraft
business because of lack of profitability, the big question must be: is
tissue-engineered skin a commercially
worthwhile product? The answer
must be yes! For example, today
Organogenesis is a profitable commercial company managed by a
team of dedicated and enthusiastic
ex-Novartis professionals. With just
1% of market share for chronic
wounds, the company is keen to
expand by moving into automation of
its process, which potentially should
reduce unit costs, increase product
consistency and thus increase sales.
Other players in the field are thinking
likewise. The way forward is undoubtedly to optimise and automate the
various steps of the process in a
pragmatic manner. This is the same
solution Henry Ford took in the early
automobile industry to expand car
ownership. Ford did not invent the
car, but he did revolutionise transportation by changing the manufacturing
process from an extremely labourintensive activity to an automated
moving assembly line. This step
change is now anticipated for tissueengineered skin. With the right
process, one day tissue-engineered
skin just may replace the bandage just
as the car replaced the horse. mdt
Chris Mason, PhD FRCS,
Regenerative Medicine Bioprocessing Unit,
Advanced Centre for Biochemical Engineering,
University College London, Roberts Building,
Torrington Place, London XC1E 7JE, UK,
tel. +44 20 7679 0140, fax +44 20 7209 0703,
e-mail: [email protected]
Wound
Care
Are you interested
in hearing
about intelligent
dressings
for wound
management
and how to
minimise
pain through
appropriate
dressing
technology?
Go to the MDT
Collaboration
Forum website
for details:
www.mdtcollaborationforum.com
fabrication and even the choice of
which cells to use varies widely. The
general recipe is to use bovine collagen
as a scaffold, add allogeneic fibroblast
cells obtained from human neonatal
foreskin to create the dermis (lowermost layer), allow this to mature for
one week before adding allogeneic
keratinocytes to produce the epithelial
layer, and then allowing the whole
bilayered construct to mature for a
further two weeks before shipping. This
is not easy to achieve. The challenges,
which are legend and have consumed
hundreds of millions of dollars,
include sterility issues, transportation
difficulties (shipping live products
with short shelf lives of a few days that
need carefully controlled temperatures)
and obtaining adequate reinbursement
from the health-care agencies.
The burns therapies (Epicel and
Myskin) are even more complex
because the patient’s own cells must
be deployed. A skin biopsy is sent to
the bioprocessing facility, cells are
extracted and expanded in number
medical device technology ❘ december 2005