Study of pressure effect on hypertrophic scar tissues

Abstract

Hypertrophic scar is a dermal fibroproliferative disorder following dermal skin trauma. This skin abnormality is characterized as raised, rigid and erythematous appearance associated with pain and pruritus. Not only would it cause severe cosmetic disfigurement, but considerable functional impairment often results if scar contracture develops over joints. Pressure therapy has been the widely applied in scar management since the early 1970s because of its non-invasive characteristics and desirable treatment effect. The optimal pressure dose, nevertheless, remains undefined, due to the lack of objective scar assessment tools and precise pressure measurement apparatus. Pressure therapy has been hypothesized to manage scarring by down-regulating fibroblast activities, however, its mechanisms have not yet been fully understood. To better understand the mechanisms, an in-vitro study was conducted to examine the biological activities of hypertrophic scar fibroblasts in response to mechanical pressure. The fibroblasts were cultured on cover-slips with diameter 13mm at a density of 2 x 10⁴under different loadings of mechanical pressures (0g, 2g, 5g and 10g) for 48 hours. Fibroblasts were harvested on Day 0, Day 2 and two days after unloading (Post-day 2) for evaluation. Inhibition of fibroblast proliferation was demonstrated upon mechanical pressure loading measured using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and the inhibition was found to be dose-dependent with higher pressure inducing a more significant effect on cell proliferation as compared to lower pressure. Similar pattern was observed in fibroblast differentiation. Immunocytochemical staining revealed an inverse relationship between pressure loadings and the population of differentiated fibroblasts (myofibroblasts). The external pressure continued to restrain cell differentiation two days after unloading. Following the in-vitro study, a randomized clinical trial with double-blinded design was conducted to explore the relationship between pressure magnitude and scar conditions. To compare the influences of two different levels of pressure on hypertrophic scars, an objective evaluation protocol was adopted to document the pressure dosage and the scar conditions. Fifty-eight post-traumatic scars which were developed for three to nine months (5.23±1.88 months) among 19 subjects were selected according to the inclusion and exclusion criteria. Scar samples were randomly assigned into two groups, namely, the low pressure group (10-15mmHg) and the high pressure group (20-25mmHg). Each patient was prescribed with two sets of tailor-made pressure garment with 5% tensile strength and insertion of pressure padding underneath the garment was used to manipulate the interface pressure generated. Objective quantification of interface pressure generated by pressure garment and padding was obtained using a pressure monitoring system, the Pliance X System, which was validated earlier in the study. For assessment of the scar maturation process, the scar thickness was measured by the Tissue Ultrasound Palpation System (TUPS), the scar color by the spectrocolorimeter and the pigmentation, vascularity and pliability by the Vancouver Scar Scale (VSS). Pain and pruritus were recorded by means of Visual Analogue Scale (VAS). Monthly assessments were performed throughout the five-month intervention period. Results demonstrated significant differences in scar conditions between high and low pressure therapy. Static pressure of at least 20mmHg was found to accelerate scar remodeling process with improved clinical presentations. It also demonstrated superior effect on reducing scar thickness. The most apparent improvement was achieved at the first month of intervention. Low pressure group also showed significant decrease in thickness. The decrease was lower and steadily decayed over time as compared to the high pressure group. Significant decrease in scar color, in terms of redness by the spectrocolorimeter, was also recorded. No significant differences were detected in pain and pruritus between the groups. Some subjects, however, reported increased pruritus especially during hot weather probably because of reduced ventilation of pressure padding. The various scar responses under different pressure magnitudes in both in-vitro study and the clinical trial indicated the importance of monitoring the interface pressure onto the scar tissue. These findings suggested that pressure garments with at least 20mmHg static pressure tend to accelerate scar maturation. Careful monitoring of interface pressure should be done to ensure better therapeutic effect in hypertrophic scar management.