Scar-improving efficacy of avotermin administered into the wound margins of skin incisions as evaluated by a randomized, double-blind, placebo-controlled, phase II clinical trial.

BACKGROUND: The authors report on a prospective, randomized, placebo-controlled phase II trial to investigate avotermin (transforming growth factor beta-3) for reducing scarring resulting from acute incised skin wounds. METHODS: Seventy-one healthy male subjects (18 to 45 years) received avotermin at 50 or 200 ng/100 µl/linear centimeter of wound margin. Subjects received three standardized 1-cm incisional wounds on the inner aspect of each upper arm. Wounds were randomized to receive (into each margin): no injection (standard wound care only), one intradermal injection of avotermin or placebo (immediately before surgery), or two injections of avotermin or placebo (immediately before surgery and 24 hours later). The primary efficacy variable was a 10-cm visual analog scale score, which assessed how closely scars resembled normal skin, administered at month 12 by an independent external scar assessment panel (a panel of lay public individuals). RESULTS: Avotermin at 200 ng/100 µl/linear centimeter, administered once or twice, achieved significant improvements in scar appearance compared with controls (p<0.02 for all comparisons). The 50-ng dose, administered twice, achieved significant improvements in scar appearance versus placebo (p=0.043). Treatment was well tolerated. CONCLUSION: These results confirm that avotermin is the first of a new class of regenerative medicines that reduce scarring when administered once or twice to the approximated margins of acute skin incisions.

Maturation of the human scar: an observational study.

BACKGROUND: The natural history of scar maturation in humans has never been formally described from either a clinical or a histologic standpoint. METHODS: The maturation of incisional scars was observed in 58 healthy male volunteers who each had 2 x 1-cm incisional wounds created on the inner aspect of both upper arms. The resulting scars were photographed digitally at monthly intervals for 12 months and excised for histologic analysis at specific time points. All histologic specimens were stained using Masson's trichrome and reviewed together with the corresponding digital clinical scar images to produce macroscopic and microscopic descriptions of the maturation process. RESULTS: Three distinct groups, each displaying a different rate of longitudinal progression of scar maturation, were identified from within the study group. The majority of volunteers belonged to a "representative" subset but distinct "poor" and "excellent" subsets were also identified. The poor subset invariably contained volunteers younger than 30 years of age, whereas the majority of the excellent subset comprised subjects older than 55 years of age. CONCLUSIONS: Scar maturation occurs as a series of defined macroscopic and microscopic stages over the course of 1 year. The rate of scar maturation varied within the study group, with older subjects (>55 years) displaying accelerated maturation, whereas a prolonged high turnover state and a retarded rate of maturation were observed in younger subjects (<30 years).

Scar redness in humans: how long does it persist after incisional and excisional wounding?

BACKGROUND: The natural history of scar redness in humans has never been formally described, and the point at which normal scar redness fades is unknown. METHODS: As part of a randomized, placebo-controlled, clinical trial investigating the effects of various doses of transforming growth factor-beta3 on scar quality, the authors observed the process of scar redness and maturation in non-drug-treated incisional and excisional wounds made on the upper inner arms of 103 volunteers. Scar photographic images were assessed by a review panel to ascertain the month during which redness faded for a particular scar. Scar histology documented the level of inflammation and angiogenesis. RESULTS: Scar redness faded at an average of 7 months. Scar redness for incisions faded significantly faster than excisions (p = 0.0001, Kruskal-Wallis test), and significant differences were also seen between anteriorly and posteriorly placed scars for incisions (p = 0.0008) and excisions (p = 0.0035), respectively. Month 12 histologic examination revealed the absence of any ongoing inflammatory processes in all scars. CONCLUSIONS: Scar redness fades on average at 7 months. This is influenced by the wound type and position. The authors advocate the use of the term "rubor perseverans" to describe the physiologic redness of a normal scar as it matures beyond the first month, a process that does not involve inflammation.

Visual analogue scale scoring and ranking: a suitable and sensitive method for assessing scar quality?

BACKGROUND: The field of scar assessment lacks a standard methodology. Previous methods have focused on a wide range of scar types, resulting in poorer sensitivity and diminishing their discriminatory effectiveness. METHODS: As part of a clinical trial investigating the scar-improving efficacy of transforming growth factor-beta3, the authors investigated the use of a visual analogue scale and scar ranking as scar assessment tools. Scar photographic images were assessed using a newly developed computerized scar assessment system by an external lay panel. RESULTS: A total of 4296 scar images were collected for visual analogue scale assessment and 2148 scar pairs were collected for scar ranking. Intrarater consistency was 100 percent for the ranking data, with differences very close to zero for the visual analogue scale consistency data. Reducing the number of assessors in the external panel significantly improved intraclass correlation coefficients. From month 1 to month 12, the correlation coefficients for the difference in visual analogue scale score showed that the assessors reliably noted the changes in the maturing scars. Combining logistic regression with an area under the curve of 0.72 in a receiver operating characteristic curve analysis, the visual analogue scale score was shown to be a highly statistically significant predictor of a good scar. CONCLUSIONS: The authors have shown the visual analogue scale scar scoring and scar ranking methods to be consistent, reliable, valid, and feasible. These methods for scar assessment are highly sensitive and capable of reliably measuring differences in scar quality, making them valuable techniques, reaching an unmet clinical need, and enabling investigation of changes in scar quality (e.g., with time or after therapeutic intervention).