Annals of
Burns and Fire Disasters - vol. XX - n. 2 - June 2000
PIEDMONT
FOUNDATION OF STUDIES AND RESEARCH ON BURNS: THE LAST THREE YEARS OF RESEARCH ACTIVITY
Teich Alasia S. Piedmont Foundation of Studies and Research on Burns, Turin,
Italy
SUMMARY. An account is given of the main activities
of the Piedmont Foundation of Studies and Research on Burns. The results of latest
research are presented, together with important developments in the field of pathological
scarring, new methods of skin cryoconservation, and peripheral sensory nerve regeneration
after extensive burns. All the Foundation's efforts endeavour to promote close and
productive links between researchers and clinicians in the field of burns in order to
achieve significant advances in this important field of medical science.
Introduction
The Piedmont
Foundation of Studies and Research on Burns continued to support research in the field of
burns related to clinical work in order to achieve its philosophy, which is to couple the
needs of clinical science with a high level of basic science, know-how, and technology.
To achieve this goal the Foundation organized meetings and up-date courses, edited
publications, and provided financial support for research.
Our efforts were , focused on certain main fields (pathological scarring, peripheral
sensory nerve regeneration, tissue banking, and cryoconservation) together with a number
of methodological projects (optimization of burn centre layouts, project for a hyperbaric
chamber for burn patients, computer assisted management of a burn centre), linked by the
common interest in burns.
We will briefly summarize the results of our research and in particular the development of
studies in the field of pathological scarring, new methods of skin ciryoconservation, and
peripheral sensory nerve regeneration after extensive burns.
Hypertrophic scarring
It is well known
that wound healing is the result of a complex interaction of biochemical mediators, cells,
and structure proteins that enables injured tissues to regain their original properties.
When normal processes in the skin are altered, pathological scarring takes place and
structural, aesthetic, and functional modifications become evident.
Post-burn pathological scarring is a very interesting field of speculation with regard
both to its prevalence, which remains very high despite therapeutic advances, and to the
complexity of its aetiopathogenesis, which remains obscure.
Recent studies have underlined the importance of the immune system in pathological
scarring. Kelman Cohen and other researchers have demonstrated an increase of circulating
immunoglobulins, the presence of anti-nucleus antibodies, and tissue immunoglobulins.
Some years ago, in collaboration with the Departments of Human Anatomy and Genetics in
Turin, Italy, we initiated research that demonstrated an increase in number and
morphological changes in Langerhans cells in the epithelium and dermis of pathological
scar tissue, together with leukocyte infiltrates. The presence of these infiltrates has
been observed in many skin diseases (i.e. lichen plarms, psoriasis, atopical dermatitis,
etc.) that are characterized by the ectopical expression of HLA class II antigens on
keratinocytes. The anomalous expression of HLA DR molecules and their modulation in the
tissues involved are concomitant to other activation molecules such as intercellular
adhesion molecule type 1 (ICAM-I), interleukin-2 receptor, and others. In the modulation
of their expression a pivotal role is played by certain cytokines secreted by
immunocompetent cells under different stimulation. Their controls are both a consequence
and a causative agent of a cascade of reactions among cells involved in extracellular
matrix remodelling.
On the basis of these considerations we decided to analyse the immunological factors of
hypertrophic scarring through a study of the modulation of cells and molecules of the
immune system directly in the affected tissue.
We then looked for different immunological activation markers in hypertrophic scars. We
also investigated the production of certain regulatory cytokines, e.g. tumour necrosis
factor (TNFa), IL-1, IL-6, interferon gamma (IFNg), and transforming growth factor (TGFb).
Briefly, our data underline that the ectopical expression of these different markers in
hypertrophic scar tissue makes it possible to group it with the derimatosis caused by an
altered immune response. In particular, the presence of these signals on keratinocytes
further demonstrates their pivotal role, a role that hitherto has been overlooked, in the
pathogenesis.
Our data also testify to the importance of fibroblasts in the evolution of scarring. The
immune system thus plays a central role as regards both the presence of abundant leukocyte
filtrates and their active status. In our opinion it is the altered co-operation between
these cells that is responsible for the pathogenesis of hypertrophic scarring, in view of
the fact that the production of cytokines, normally involved in extracellular matrix
remodelling, shows a major impairment that leads to a disruption of the orchestration of
messages regulating cell interactions.
It still has to be clarified whether an exogenous signal or a genetic predisposition can
be considered the direct cause of hypertrophic scarring.
Analysis of cryoconservation techniques
and quality controls
In recent years there has
been an increasingly urgent need for cadaver skin in up-to-date treatment of extensive
burns. For this reason the Foundation supported a programme for the analysis of different
protocols for the cryoconservation of alloplastic skin. In particular, some studies were
conducted for the assessment of tissue viability after freezing in order to standardize
protocols for the harvesting, transport, and stocking of tissues in a regional tissue
bank.
Peripheral nerve
regeneration
The sensory recovery of
transplanted skin is a fundamental feature that signifies the functional success of
reconstruction. Sensory regeneration was discussed for many years: some researchers
believed that clinical sensory recovery was due to structures surviving in the wound bed
(like feeling through a glove), others suggested the regeneration of new structures in the
transplants. One much discussed point was the survival of capsulated receptors and their
reinnervation. Various conflicting data were obtained in different experimental conditions
using unselective and repetitive histological techniques (heavy metal impregnation).
Research conducted in collaboration with the Department of Human Anatomy of the University
of Turin led to the implementation of an immunchistochemical technique for the detection
of a selective neural marker that repetitively stains all nerve structures in both normal
and transplanted skin. This is a structural protein of all classes of nerve fibres,
including autonomic fibres. Staining with this marker made it possible to demonstrate the
presence of intra-epithelial fibres that are not yet clearly evident and to confirm the
classification of capsular receptors (Meissner's corpuscles and simple coiled corpuscles,
while all the others that are classically reported have to be regarded as artefacts). Our
studies on scars, skin flaps, and skin grafts showed evidence of the regeneration of nerve
structures as far as the superficial layers, but with a lower density than that of normal
skin. Fibres spread from a deep dermal plexus into the dermal papillae, mainly terminating
as dermal nerve endings or, less frequently, in contact with Merkel cells or as free
intra-epithelial nerve endings. Skin flaps have been shown to contain capsulated
receptors, although these were aberrantly reinnervated.
These findings conflict with the widely held opinion that scars and transplanted skin fail
to regenerate and that sensory recovery depends uniquely on structures surviving in the
wound bed.
Conclusions
Our efforts are thus aimed
at establishing a close and productive relationship between researchers and clinicians in
the field in order to achieve results of the greatest scientific significance in the
stimulating field of burns.
RESUME. L'Auteur
décrit les activités principales de la Fondation Piémontaise des Etudes et de Recherche
sur les Brûlures. Les résultats des recherches les plus récentes sont présentées,
comme aussi les développements importants dans le secteur de la cicatrisation
pathologique, les nouvelles méthodes de la cryoconservation, et la régénération des
nerfs sensoriels périphériques aprés les brolures étendues. Tous les efforts de la
Fondation cherchent à promouvoir des rapports étroits et efficaces entre les chercheurs
et les cliniciens dans le secteur des brûlures pour obtenir des progrés significatifs
dans cet important secteur de la science médicale.
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Report presented by the President, Professor Simone Teich Alasia,
at the Third International Conference on Burns and Fire Disasters,
Palermo, Italy, June 1995, and confirmed by the author in September 2000.Address
correspondence to:
Prof. Simone Teich Alasia,
Fondazione Piemontese per gli Studi e le Ricerche sulle Ustioni,
Via Zuretti 29, 10126 Turin, Italy
(tel.: 0ll 6967998) |
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