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Development of a biodegradable scaffold for dermo-epidermal skin grafts

Objective


Da nord a sud freddo, neve e temperature sotto lo zero: una donna morta assiderata in Val Venosta. Nella notte una formazione ghiacciata si è abbattuta sul tetto di una casa sfondandolo, nessun ferito.
A major unresolved clinical problem in wound care is the
possibility of providing an adequate coverage to severely
burned patients thus enabling an efficient restoration,
under both a functional and a cosmetic point of view, of
the injured sites. A more widespread pathology in the
wound healing area is the treatment of non healing ulcers,
essentially, venous stasis ulcers and pressure ulcers.
More than 1% of the total worldwide population is
affected by leg ulcers: more than half of these ulcers tabe
longer than 9 months to heal. Although the number of
sophisticated dressings available on the market is
dramatically increasing, the rate of sucess in the use of
such dressings for critical lesions, where healing is
impaired, is generally quite limited. There is therefore
a growing demand for improved treatments that will help
heal problematic wounds. Cultured keratinocytes grafting
is now established as a treatment option in severe burned
patients and has a place in the clinical management of
other wounds, particularly chronic venous ulcers. The
principal drawbacks associated with the production of
cultured keratinocyte grafts and with their use in the
burn scenario are the fragility and the difficulty to
handle the cultured layer and, more important, the
limited take rate on the wound bed and the excessive
scarring and wound contraction associated with the
grafting. The high costs of keratinocyte culture limit
its routine use in more widespread pathologies such as
chronic ulcers, despite excellent clinical results.


The present proposal involves the production of an
innovative multilayered biodegradable hyaluronic acid
based scaffold that will efficiently support epidermal
cell proliferation and act as a scaffold for neo dermal
tissue, thus providing an improved and cost effective
treatment for critical wounds. Hyaluronic acid is a
naturally occurring extracellular matrix (ECM) molecule,
which offers the advantage of being recognized by cell
receptors, of interacting with other ECM molecules and
of being metabolized by intrinsic cellular pathways. The
ability to chemically modify hyaluronic acid without
altering the biological properties of the matrix molecule
enables the production of novel, highly biocompatible
derivatives with increased longevity in vivo. The device
to be developed is composed of a thin top hyaluronan
based membrane underlying a more diffuse, sponge like
three dimensional structure which will provide the
scaffold for a seeded dermal replacement. Perforations in
the membrane will allow access for epidermal cells to the
dermis, thus enabling the efficient formation of dermo
epidermal junctions, which are critical in providing
strength to the newly formed skin. Hyaluronic derivatives
will be synthetised and processed into appropriate tissue
inducing scaffolds. The mechanical physical and surface
properties of the device will be investigated. The
architecture of the scaffold will be optimized by
performing extensive in vitro characterization of cell
viability, once keratinocytes and fibroblasts have
populated the device. The scaffold degradation rates will
be adjusted to match the rate of tissue regeneration. The
"living" dressing, seeded with epidermal and dermal cells
will be tested in small and large animal models to
evaluate its efficacy. Preliminary controlled clinical
trials on burn wounds and on chronic ulcers will be
conducted. The clinical objectives of the trial on burn
victims will be to increase the take rate of the grafts
on the wound bed, the overall cosmetic appearance of the
restored organ as well as to decrease wound contraction.
The clinical objective of the trial on venous ulcers will
be to demonstrate that skin grafts may have a beneficial
effect on the healing of chronic ulcers by stimulating
the repair process of these torpid wounds. In both trials
an accurate evaluation of the total cost of treatment
will be performed, in order to assess the cost/benefit
issues correlated to this innovative therapy.


The proposers believe that keratinocyte/fibroblast/matrix
interactions are of such significance that a combination
of keratinocytes and fibroblsts within a hyaluronan based
biodegradable scaffold will significantly improve the
clinical outcome of critical wounds and as a consequence,
this will favorably impact the patients' quality of life
and significantly reduce the healthcare expenditure
correlated to the treatment of problematic wounds

The partners of the project feel that this collaboration
will enhance and advance the technology of skin grafting
and should place Europe as a major player in this field.
Improvements in competitiveness will arise through the
availibility of novel biodegradable scaffolds, and the
recognized ability to effectively market innovative
product concepts, offering a competitive advantage over
established non European manufacturers.

Coordinator

FIDIA ADVANCED BIOPOLYMERS SRL
Address
Via Ponte Della Fabbrica 3/B
35031 Abano Terme
Italy

Participants (5)

AACHEN UNIVERSITY OF TECHNOLOGY
Germany
Address
30,Pauwelsstraße 30
52057 Aachen
Marka Arzneimittel GmbH
Germany
Address

60090 Frankfurt Am Main
PARCO SCIENTIFICO E TECNOLOGICO AREA IONICO SALENTINA - CENTRO NAZIONALE PER LA RICERCA E LO SVILUPPO DEI MATERIALI SCPA
Italy
Address
S.s. 5 Appia Km 714
72023 Brindisi
Queen Mary and Westfield College - St. Bartholomews and The Royal London School of Medicine & Dentistry
United Kingdom
Address
2 Newark Street
E1 2AT London
Stiftung Deutsches Krebsforschungszentrum
Germany
Address
280,Im Neuenheimer Feld
69120 Heidelberg