DERMOFUNCTIONAL TREATMENT OF HYPERTROPHIC BURN SCARS

De Santis P., Savoia A.

Department of Plastic Surgery and Burn Unit, Brindisi, Italy

SUMMARY. A review of the pathology of hypertrophic bums is followed by an analysis of the results of a study of twenty consecutive patients with hypertrophic bum scars. The patients were treated with Synchroline, a cream compound consisting of an association of functional substances capable of stimulating the biosynthesis of the macromolecules responsible for skin pliability and elasticity The criteria for the selection of patients were the presence of deep hypertrophic bum scars, an average burned surface of 20%, and the use of pressure garment therapy. Each patient treated was matched with a control patient selected among patients treated by other physicians working in the same Burn Unit. The patients were matched for age group, scar site, and duration of treatment with hydrating creams and pressure garments. All the patients were followed up monthly and the scar was assessed by a physician in the Burn Unit who was unaware of the patients' group membership. The following scar characteristics were assessed: appearance, consistency, presence of nodules, coloration, and presence of ulcers. One patient underwent two hypertrophic scar biopsies: at the beginning of treatment and after six months. Our results indicate that hypertrophic scars in the Synchroline group were more elastic and pliable at six months than those in the hydrating cream group. The effect of Synchroline as a precursor and stimulator of hyaluronic acid, fibronectin and soluble collagen biosynthesis is discussed.

Hypertrophic scars are a frequent outcome after the healing of deep bums and represent the greatest disorder of the scarring process. The main features of hypertrophic bum scars are the continuous production of collagen, a remodelling defect in cell structure and the extracellular matrix, the abundant presence of infiltrated cells, and the absence of elastic fibres. Morphologically, hypertrophic bum scars present a less mucoid matrix, together with collagen hyaline fibres. Elastic fibres are less numerous or absent. The fibroblasts assume the structure and properties of smooth muscles in the contraction processes of granulation tissue. These modified fibroblasts, or myofibroblasts, that are observable in granulation tissue after the formation of collagen fibres are important in establishing the direction of the fibres.
In hypertrophic scars, myofibroblasts are ineffective in establishing the direction of the collagen mass.These structural differences in the hypertrophic scar may be responsible for differences in mechanical properties, such as increased stretch resistance. The increase in collagen deposited in hypertrophic scars has been thought to be due to increased synthesis or a deficit in collagen lysis .... .. Collagen synthesis is greatly increased, while at the same time there is a decrease in the availability of active collagenase. The enzymes involved in the transformation of protocollagen into collagen are proline hydroxylase and lysine hydroxylase. Their activity increases considerably in granulation and scar tissue. The increase in collagen synthesis may be due to the increased number of actively secreting fibroblasts or to increased enzymatic activity.
Hypertrophic scars contain large amounts of type III collagen. This substance may affect the resistance of fibres to stretch and thus be responsible for the different stretch resistance shown by normal dermis and by bum tissue.` The hydroxylysine and hexose content of the dermis and the scar is different. Collagen is catabolized by collagenase, a proteolytic enzyme available in inactive form in the skin and inhibited by the alpha globins.` It has been hypothesized that this inhibition is more marked in hypertrophic scars. A higher concentration of chondroitin-4-sulphate (proteoglycans) has been observed in nodular areas of hypertrophic scars.` The increased concentration of proteoglycans, coupled with large amounts of chondroitin-4sulphate, contributes to the overdeposition of collagen.
Hypertrophic scars display an increased amount of glycosaminoglycan-proteoglycan, and a three-dimensional architecture compared with normal scars. The increase in glycosaminoglycans may protect collagen from collagenase remodelling, thus allowing it to be stored. This mechanism may also be responsible for scar hypertrophy. The amount of dermatan sulphate is highly reduced in hypertrophic sears, especially in areas where collagen turns spiral-shape. The quantity of glycosaminoglycans and hyaluronic acid in the scar varies: there may be a close relationship between glycosaminoglycan-collagen and collagenase activity, as they interact in such a way that any modification of one factor affects all the others. Hyaluronic acid limits the conversion of extensible soluble collagen to rigid insoluble collagen, slowing down the formation of intermolecular cross links. The organization of collagen fibrils may be related to the quantity and type of proteoglycans, which possibly influence the growth and remodelling of the extracellular matrix - the links between proteoglycans and collagen are in fact stronger in hypertrophic scars and can stabilize the plot of collagen fibrils?' The newly produced collagen is unevenly stored in the hypertrophic scar, where it adheres through rapid intermolecular formation of crosslinking, giving the fibrils increased resistance to stretch. A slowdown of this process would give collagen molecules a more physiological organization. It has been hypothesized that a temporary delay in collagen cross-link formation may facilitate tissue remodelling and thus create softer tissue.
Synchroline is an association of functional substances capable of stimulating the biosynthesis of the macromolecules responsible for skin elasticity and pliability. The components of Synchroline are as follows: Asian acid from Hydrocotyle extract; N-acetyl-D-glucosamine; proline linoleate, proline linolenate, and proline arachidonate; and the reduced enzymatic fraction of fibronectin. The effect of Synchroline is that of both stimulator and precursor of hyaluronic acid, fibronectin and soluble collagen biosynthesis. Asian acid, which is responsible for Synchroline's stimulatory effect on the amorphous and fibrous component of the dermis, acts directly on collagen biosynthesis, improving its quality. This effect is apparently due to the increased incorporation of fibrin in the fibroblast. Proline linoleate is the precursor of collagen present in Synchroline and guarantees the amino acid necessary for collagen biosynthesis. The combined action of Asian acid and proline linoleate stimulates collagen biosynthesis. Asian acid stimulates use of the acetate in the glycosaminoglycans. N-acetyl-D-glucosamine is a natural molecule and an active metabolite of UDP-N-acetylglucosamine, which is essential for the formation of the monomer of hyaluronic acid after conjugation with glycuronic acid.

Fig. 1 - Patient with hypertrophic burn scar in right shoulder. Elastocompressive and topical therapy initiated two weeks after healing. Fig. 2 - Result after six months treatment.

The combined action of Asian acid and N-acetylD-glucosamine enables Synchroline to support production of hyaluronic acid. An increase in the biosynthesis of fibronectin on the fibroblast walls has been observed with Asian acid. The reduced enzymatic fraction of fibronectin available in Synchroline is characterized by the presence of the tetrapeptide I-arginyl-glycyl-l-aspartyl-l-serine,which is the fragment of the molecule responsible for the cell's adhesiveness. This fraction acts as a precursor of fibronectin biosynthesis.

Twenty consecutive patients were treated for six months with Synchroline, an association of functional substances able to stimulate the biosynthesis of the macromolecules responsible for skin elasticity and pliability.
The criteria for the selection of patients were deep hypertrophic bum scars, an average bum surface of 20%, and the use of pressure garment therapy. Each patient was matched with a control patient, selected among patients treated in the same Burn Unit. Each patient was matched as regards age group, scar site, and duration of treatment with hydrating creams or pressure garments (Tab. 1). In all, forty patients were recruited and followed up monthly.

A number of scar characteristics were assessed at the beginning of treatment and after six months; assessment was performed by a specialist in the Burn Unit who was unaware of the patients' group membership. The major points considered and evaluation criteria were:

• scar appearance (photographs before treatment and after six months)
• scar consistency (resistance): retracting, 5 points; compact, 3 points; soft, I point
• palpation: with solid nodules, 5 points; with soft nodules, 3 points; without nodules, 1 point
• coloration: intensely hypaeremic, 5 points; moderately reddened, 3 points; similar to surrounding skin, I point
• One patient treated with Synchroline underwent two scar biopsies: one at the beginning of treatment and the other after six months.

The two groups of patients were comparable as regards their main characteristics. Scar evaluation results at six months are presented in Table II.

The hypertrophic scars of the Synchroline-treated patients were more pliable and elastic than those in the hydrating cream group. Another remarkable result was the lack of ulcers in the crisis areas in Synchroline-treated patients. This early and better response may be due to the effect of the association of functional substances on the production of hyaluronic acid, fibronectin, and soluble collagen.

RESUME. Les Auteurs, après avoir considéré la pathologie des cicatrices hypertrophiques dues aux brûlures, analysent les résultats d'une étude de vingt patients consécutifs atteints de cicatrices hypertrophiques dues aux brûlures. Les patients ont été traités avec Synchroline, un composé crémeux qui consiste en une association de substances fonctionnelles capables de stimuler la biosynthèse des macromolécules responsables de la flexibilité et l'élasticité de la peau. Les critères pour la sélection des patients étaient la présence de cicatrices hypertrophiques profondes dues aux brûlures, une surface brûlée moyenne de 20%, et l'emploi de la pressothérapie. Chaque patient traité a été confronté avec un patient témoin, sélectionné parmi les patients traités par d'autres médecins de la même Unité de Brûlures. Les patients ont été confrontés sur la base de l'âge, le site de la cicatrice, et la durée du traitement avec les crèmes hydratantes et la pressothérapie. Tous les patients ont été contrôlés tous les mois quand la cicatrice a été évaluée par un médecin de l'Unité de Brûlures qui ne connaissait pas la division des patients en groupes. Les caractéristiques suivantes des cicatrices ont été évaluées: aspect, consistance, présence de nodules, coloration, et la presence, d'ulcères. Un patient a subi deux biopsies des cicatrices hypertrophiques: au commencement du traitement et après six mois. Les résultats de l'étude indiquent que les cicatrices dans le groupe traité avec Synchroline étaient plus élastiques et flexibles à six mois que celles du groupe traité avec la crème hydratante. Enfin, les Auteurs discutent l'effet de Synchroline comme précurseur et stimulateur de l'acide hyaluronique, de la fibronectine et de la biosynthèse du collagène soluble.