|Ann. Medit. Burns Club - vol. V111 - n. I - March 1995
PATHOLOGICAL SCAR FORMATION IN BURNS: NEW BIOCHEMICAL AND MOLECULAR FACTORS IN THE HEALING PROCESS
Bocchi A., Caleffi E., Toschi S., Stabile M.
Cattedra di Chirurgia Plastica, UniversitA clegli Studi e Divisione di Chirurgia Plastica, USL 4, Parma, Italy
SUMMARY. A review is made of the principal biochemical and molecular factors that have most recently come to light in research into the processes involved in pathological scar formation due to bums. A better understanding of the biochemical events leading to pathological scar formation will help to improve prevention and therapy. The various vascular changes following tissue injury are considered, as well as the question of tissue repair. As shown by the most up-to-date research, it is now possible to accomplish the pharmacological and non-surgical therapy of burn scars by means of both chemical and physical agents. These various agents are systematically reviewed. Among the chemical agents, corticosteroids and zinc are considered to be the first-choice drugs; while among the physical agents, pressure would appear to be the most effective.
The principal steps of scar formation
have been known for many years.
Elements of molecular physiopathology
Vascular changes are the first event
following tissue injury: these consist of a brief period of vasoconstriction followed by
vasodilatation and at the same time haemocoagulation.
Another important step is the repair of lost tissue through collagen deposition proliferation, vascular buttons from wound margins and epithelialization. Wound contraction then follows, regulated by myofibroblasts, through the centripetal movement of the injured margins of the wound.To examine closely the biomolecular aspect of the healing process we must consider:
We will now consider the pathogenetic
aspects of abnormal scar formation.In hypertrophic scars and keloids, collagen synthesis
is considerably increased; the arrangement of collagen fibres is not parallel to the
epithelium,~ as in normal scars, but random. There is also a disequilibrium between
collagenase because the collagen is covered by a coat of proteoglycans, which interfere
with the activity of the enzyme.
Pharmacological aspects and therapy
In the light of the above molecular studies, the pharmacological and non-surgical treatment of burn scars may be accomplished through both chemical and physical agents.
Among the chemical factors which have proved useful for clinical application are lathyrogenic agents: BAPN and penicillamine, which inhibit collagen crosslink.
Better results are obtained through the association with colchicine, which stimulates collagenase activity.
However, further controls on therapeutic effectiveness and collateral effects must be carried out before routine clinical use is possible.Enzymes, in spite of their promising theoretical advantage (collagen degradation), have not yet achieved satisfactory clinical results.Corticosteroids are the most successful agents in the non-surgical therapy of burn scars. A few mechanisms of their action are known: they decrease collagen synthesis, inhibit fibroblast migration into the wound, and affect the inflammatory and local immune response. Collateral effects may be decreased by injection within the scar; inoculation in contiguous and underlying tissues should be avoided.0.05% retinoic acid solution given to burn patients twice a day for a few months can decrease the size of the lesion, possibly because of the inhibition of fibroblast and lymphocyte growth.
Vitamin E is a membrane stabilizer which inhibits the liberation of lysosomal contents, having an anti-inflammatory effect which decreases tissue repair.Zinc seems to inhibit fibroblast action, although there are reports of a stimulation of collagen synthesis.The physical agents employed in the treatment of hypertrophic and keloid scars in burn patients are irradiation and pressure.
Irradiation has a particularly favourable action on keloids associated with surgery and, in some cases, with chemotherapy. Nevertheless it should be employed only in carefully selected cases (failure of other therapies, multiple or relapsed lesions) because of the risks of late complications (radiodermitis, radionecrosis).
Pressure represents the basic moment of non-surgical treatment of a scar following a third-degree burn. Its mechanism lies in the induction of tissue hypoxia for a period of at least 12 to 18 months. The best results are obtained in the limbs; in the face, because of the irregular distribution of the pressure forces, only the cheeks and forehead receive uniform pressure.
Some clinical improvement has been observed in recent years by many researchers using silicone gel treatment in hypertrophic burn scars. The mode of action remains to be determined, but it is not due to pressure, temperature, oxygen tension or occlusion.
The above-described molecular
mechanisms achieve their best expression in burned tissue repair because the burn injury
produces an amplification of the inflammatory response, fibroblast activity and, in
general, every physical response to trauma.
RESUME. Les auteurs considèrent les principaux facteurs biochimiques et moléculaires qui ont été découverts au cours des recherches les plus récentes sur les processus de la formation pathologique des cicatrices causées par les brûlures. La compréhension plus exacte des événements biochimiques qui conduisent à la formation pathologique des cicatrices sera utile pour améliorer la prévention et la thérapie. Les auteurs décrivent les diverses modifications vasculaires à la suite des lésions tissulaires et la question de la réparation tissulaire. Grâce aux dernières recherches en la matière, il est maintenant possible d'effectuer la thérapie pharmacologique et non chirurgicale des cicatrices dues aux brûlures moyennant des agents tant chimiques que physiques. Sur la base d'une étude systématique de tous ces agents les auteurs concluent que pour ce qui concerne les médicaments chimiques les corticostér6ides et le zinc sont les plus indiqués, tandis que pour les agents physiques la pression semble être la méthode la plus efficace.