Treating skin wounds and lesions in a way
which is both effective and aesthetic remains an outstanding medical
problem. While the first thing that springs to mind is healing the
wounds of severe burn victims - almost 20 000 in Europe every year
- this problem concerns many other patients, too. Approximately
1% of the world population is affected by chronic venous ulcers
due to heart diseases which reduce their healing capacity; the skin
lesions, which primarily affect the legs, can take more than nine
months to heal. Diabetics, of whom there are more than 10 million
in Europe, are also vulnerable and frequently suffer from wounds
to the feet; these lesions lead 60 000 of them every year to undergo
amputation, which could be avoided if efficient skin reconstruction
procedures existed. Finally, the need for artificial skin also affects
individuals suffering from serious hereditary skin diseases, such
as bullous epidermolysis, which require reconstructive surgery.
At the present time, skin grafts are also used to this end. Epidermal
cells are cultivated in the laboratory in order to obtain a fine
layer of cells which may be grafted onto the wound. This reconstituted
skin is nevertheless delicate to handle on account of its fragility
and has the disadvantage of retracting too greatly during the healing
process. What is more, the high cost of this process reduces the
extent to which it can be used.
A polysaccharide matrix
It was in this context that Fidia Advanced Biopolymers (Italy)
conceived the creation of an artificial skin combining biomaterials
with living cells. This company proposed to manufacture a fabric
which would permit the multiplication of epidermal cells (keratinocytes)
on one side and dermal cells (fibroblasts) on the other. Holes arranged
at regular intervals would make it possible to form links between
the two tissues and thus would guarantee the solidity of the newly
The first difficulty with a project of this kind is the choice
of an adequate support, namely one which is accepted by the human
body, which is biodegradable and which permits skin cell seeding
and harmonious development. The company opted for a molecule which
is naturally present in intercellular spaces: hyaluronic acid. This
polysaccharide has the advantage of being recognised by the molecular
receptors, of being degradable by the organism and of being capable
of being modified chemically without losing its biological properties.
So researchers studied the physical properties and surface of hyaluronic
acid derivatives and tested their pace of decomposition so that
they would correspond to that of the skin reconstitution.
A second difficulty was that of preserving the desired organisation
of tissues when several types of cells co-exist on the same support.
This question initially led the researchers to study the dermal
and epidermal parts separately. They developed derivatives of hyaluronic
acid which could be used to make a scaffold consisting of a fine
membrane destined to receive the epidermal cells and a thicker structure,
which was three-dimensional and spongy, destined to receive the
dermal cells. Within the framework of the project Development
of a biodegradable scaffold for dermo-epidermal skin grafts
under the Brite-Euram programme on biomaterials, European cooperation
made it possible to bring together people with very different skills
and to achieve the critical mass needed to develop a product of
this kind. "One of our partners, for example, works in the
textile industry. He proved to be indispensable for adapting the
technology of non-woven products, used in the manufacture
of materials such as Kleenex, to the production of the matrix,"
explains Alessandra Pavesio, researcher at Fidia and coordinator
of the project.
Reconstruction in two stages
Two first-generation systems, one for each of the two types of
cell, have been produced and are now being commercialised in Italy.
The patient's fibroblasts and keratinocytes are separated after
biopsy and cultivated separately. The dermal matrix is then applied
to the wound and the vascularisation of this tissue is awaited before
the epidermal layer is positioned. The whole procedure lasts about
The next stage consists of applying to the same support - which
is smooth on one side and spongy on the other - the keratinocytes
and the fibroblasts. "The main advantage of a single-stage
system will be to simplify and shorten the procedure. This new matrix
ought to be ready for clinical trials within a year and a half,
but we will still have to wait another two or three years before
we can hope to commercialise it", specifies Alessandra Pavesio.
Only one competitive product based on the same principle currently
exists: a matrix in collagen of bovine origin developed by the firm
Organogenesis, the licence for which has been ceded to Novartis.
"Apart from the fact that it is unlikely to be widely accepted
in Europe on account of its animal origin, the use of a protein
in this system may provoke autoimmune reactions. What is more, this
process uses donor cells, which does not facilitate their integration
into the reconstructed skin", pursues the project coordinator.
The immunological neutrality of hyalonuric acid and the autologous
grafting of skin cells thus constitute the major advantages of the
Italian product. These specific qualities are helping to place Europe
in a good position in a highly competitive field which, up to the
present time, has included very few industries from the old continent.
Fidia Advanced Biopolymers is now envisaging extending this research
to create matrices adapted to other soft tissues, such as adipose
tissues, for the reconstruction of breasts after therapeutic ablation.
Development of a Biodegradable Scaffold for Dermo-Epidermal
Brite EuRam III
Fidia Advanced Biopolymers
Fax : +39 0 49 82 32 752
E-mail : firstname.lastname@example.org
- Fidia Advanced Polymers, Abano Terme, Italy
- Centro Nazionale per la Ricerca e lo Sviluppo dei Materiali
Sepa (PASTIS), Brindisi, Italy
- Rheinisch-Westfälische Technische Hochshule (RWTH),
- Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany
- Queen Mary & Westfield College, London, United Kingdom
- Houget Duesberg Bosson (HDB), Ensival (Verviersl), Belgium.
Image obtained with an electronic microscope
showing human skin fibroblasts growing and multiplying by adhering
to the structure in biocompatible Laserskin® material developed
by the FAB company.