Recommendations on clinical proof of efficacy for potential scar prevention and reduction therapies.

Cutaneous scarring is an enormous medical problem with approximately 100 million patients acquiring scars each year. Scar prevention/reduction represents a significant, and largely unmet, clinical need. Research into the prophylactic modulation of scar outcome differs from research into other disease processes as the scar is not present at the start of the study; measurements of changes from baseline are impossible. Final scar morphology is influenced by many variables. A fundamental principle that should be observed in the prospective evaluation of scar prevention/reduction therapies is that, if left untreated, wounds in treatment and control groups should have healed with identical scars. Observation of this principle will allow the detection of true treatment effects. The many variables that influence scar morphology mean that the evaluation of potential pharmaceutical products for this indication favors the use of self-controlled designs in clinical trials. In this article, we review variables that affect scar morphology and recommend the self-controlled design for clinical trials aiming to establish proof of efficacy of scar prevention and reduction pharmaceuticals. With no pharmaceutical products currently licensed for this indication, this represents a new therapeutic area. The principles discussed will also have direct relevance to the wider fields of wound healing and regenerative medicine.

Avotermin for scar improvement following scar revision surgery: a randomized, double-blind, within-patient, placebo-controlled, phase II clinical trial.

BACKGROUND: Skin scarring is associated with psychosocial distress and has a negative effect on quality of life. The transforming growth factor (TGF)-ß family of cytokines plays a key role in scarring. TGF-ß3 improves scar appearance in a range of mammalian species. This study was performed to assess the efficacy of intradermal avotermin (TGF-ß3) for the improvement of scar appearance following scar revision surgery. METHODS: Sixty patients (35 men and 25 women; age, 19 to 78 years; 53 Caucasians; scar length, 5 to 21 cm) received intradermal avotermin (200 ng/100 µl/linear cm wound margin) and placebo to outer wound segments immediately after, and again 24 hours after, complete (group 1) or staged (group 2) scar revision surgery. A within-patient design was chosen to control for interindividual factors that affect scarring. The primary efficacy variable was a total scar score derived from a visual analogue scale, scored by a lay panel from standardized photographs from months 1 through 7 following treatment. RESULTS: : Primary endpoint data from the combined surgical groups showed that avotermin significantly improved scar appearance compared with placebo (total scar score difference, 21.93 mm; p = 0.04). Profilometry showed a greater reduction in scar surface area from baseline with avotermin treatment compared with placebo, significant in group 2 at months 7 and 12 (difference, 41.99 mm and 25.85 mm, respectively; p = 0.03 for both comparisons). Histologic analysis from group 2 showed that, compared with placebo treatment, collagen organization in avotermin-treated scars more closely resembled normal skin in 14 of 19 cases. Avotermin was well tolerated. CONCLUSION: Avotermin administration following scar revision surgery is well tolerated and significantly improves scar appearance compared with placebo. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.(Figure is included in full-text article.).

Dynamic skin tension in the forearm: effects of pronation and supination.

PURPOSE: Longitudinal scars on the radial quadrant of the distal forearm skin envelope are typically observed to be wider than those on the ulnar quadrant and have an increased incidence of hypertrophic change. Forearm rotation movements may produce differential skin tensions within the forearm skin envelope, and this may lead to differential scarring patterns. This study was designed to measure skin tension changes in the forearm as a result of rotational position to see if these would be consistent with the hypothesis that greater tension changes are observed on the radial aspect of the forearm. METHODS: The effect of forearm position on the magnitude and direction of skin tension was measured on human volunteers. Standardized circles were marked in circumferential fashion at specified intervals on forearm skin, and the angular and dimensional distortion of these circles that occurred with forearm rotation was measured with caliper and goniometer. Data were analyzed for statistical significance using paired t-test. RESULTS: Pronation and supination resulted in marked angular rotation of the lines of maximal skin tension at all sites on the forearm. Supination resulted in a greater angular deviation of the lines of maximal skin tension from the longitudinal line of usual surgical incision, particularly on the radial aspect of the forearm. In supination, the magnitude of ellipsoid deformation at the distal forearm was greater on the radial aspect compared with that of the ulnar. Similar significant changes were also demonstrated at the mid-forearm and proximal forearm levels. CONCLUSIONS: This study systematically maps the effects of pronation and supination on skin tension within the forearm skin envelope. The significant changes occurring in both the ellipsoid deformation and ellipsoid orientation support our hypothesis that the magnitude of skin tension changes significantly with forearm rotation. The radial aspect of the distal forearm experiences the greatest changes, particularly as the forearm supinates.

Skin tension or skin compression? Small circular wounds are likely to shrink, not gape.

The final appearance of a scar may be influenced by tension or mechanical factors [Borges AF. Scar prognosis of wounds. Br J Plast Surg 1960;13:47-54; Arem AJ, Madden JW. Effects of stress on healing wounds. J Surg Res 1976;20:93-102; Burgess LP, Morin GV, Rand M, et al. Wound healing. Relationship of wound closing tension to scar width in rats. Arch Otolaryngol Head Neck Surg 1990;116:798-802; Meyer M, McGrouther DA. A study relating wound tension to scar morphology in the pre-sternal scar using Langer's technique. Br J Plast Surg 1991;44:291-4] Karl Langer suggested that information could be gained about the tension inherent in skin, in all directions, by observing the wound edge retraction that occurred after making circular skin incisions [Langer K. On the anatomy and physiology of the skin II. Skin tension. Br J Plast Surg 1978;31:93-106]. Circular wounds may be used to demonstrate the orientation of the dominant axis of 'tension' in the skin but is this always a tensile stress as opposed to a compressive stress? This is the second article in a series documenting the mechanical properties of circular punch biopsy wounds. The aim of this study was to make detailed observations of the dimensional distortions of circular wounds on the face and neck, from which deductions could be made with regard to mechanical stress. One hundred and seventy-five benign head and neck lesions were excised from 72 volunteers using circular dermal punch biopsies. The distortions of the resulting wounds were observed to be elliptical in most cases. Measurements were taken of the maximum and minimum diameters of the wound and expressed as ratios of the size of the punch biopsy used for excision. The change in area from the area of the punch biopsy to that of the wound was also calculated. The maximum diameter of the wound was smaller than the diameter of the punch biopsy in 40.6% of cases, the minimum diameter of the wound was smaller in 97.7% of cases and the area of the wound was smaller than that of the punch biopsy in 90.3%. These dimensional changes varied between sites (P=0.0005, P=0.0001 and P<0.0001, respectively). We conclude that the reported rhomboidal or lattice structure [Ridge MD, Wright V. The directional effects of skin. A bioengineering study of skin with particular reference to Langer's Lines. J Invest Dermatol 1966;46:341-6] of skin has individual components which are under tensional force due to elastic retraction. Wounds smaller than the rhomboidal unit will reduce in area, due to the intact tensional forces in the individual dermal components, giving an appearance of the skin overall being under compression. Larger wounds, disrupting more of the lattice structure, will gape.

Optimal plaster conformation derived using a custom-made jig to obtain maximum strength of protective plaster of Paris for hand surgery.

BACKGROUND: Surgical repair of soft tissue trauma in the upper limb frequently requires postoperative immobilization to prevent tension across repaired tendons, vessels, or nerves. A plaster of Paris backslab, placed on either the volar or the dorsal surface, is frequently used, as it is inexpensive and easy to apply. METHODS: In an effort to improve upon the strength of plaster of Paris backslabs, we designed a custom-made jig to subject angled backslabs (n = 5 per group) of various designs to a torsional force. We tested 10-layered backslabs with 0, 1, or 2 ridges and 15-layered backslabs without ridges. RESULTS: We demonstrate that the addition of longitudinal reinforcing ridges on the convex surface of backslabs can improve simple backslabs in terms of breaking strength, plaster stiffness, and failure load. The optimal design employs a single, centrally placed ridge, which provides the maximum support in the axis of the net force acting across the angle, the fulcrum of angle backslabs. The formation of two parallel longitudinal ridges does not offer any additional support. CONCLUSIONS: Backslabs can be strengthened significantly by placement of a single reinforcing ridge. This allows plaster weight and thickness to be kept to a minimum, reducing the setting time of the plaster and contributing to patient comfort. These findings demonstrate the ideal construction of angled plaster of Paris backslabs for the protection of soft tissue repairs.