| Author: | Li, Pan |
| Title: | Pressure therapy for management of post-burn hypertrophic scarring : effects and mechanism |
| Advisors: | Li, Cecilia (RS) |
| Degree: | Ph.D. |
| Year: | 2020 |
| Subject: | Hypertrophic scars -- Care Pressure -- Therapeutuc use Hong Kong Polytechnic University -- Dissertations |
| Department: | Department of Rehabilitation Sciences |
| Pages: | xxi, 194 pages : color illustrations |
| Language: | English |
| Abstract: | Background: Burn injuries are among the major causes of morbidity and mortality worldwide, ranked as the fourth most common type of trauma. Despite recent advances in burn care and increases in survival rates after burn injury, the development of hypertrophic scarring after burn injury remains one of the greatest barriers to function and the most visible stigma of injury. Hypertrophic scarring (HS) is a common and frustrating complication after burn injury. Pressure therapy was considered to be the mainstay non-invasive treatment for HS, but the clinical practice of this therapy varies among medical centres. There is a lack of standardisation regarding the primary factors that might influence the effects of pressure therapy, including the timing of intervention, the pressure dose and regular monitoring. Moreover, how pressure therapy influence the scar maturation process has seldom been reported. The mechanism of pressure intervention for HS thus remains unclear. Hence, the application of pressure for scar management has been challenged in the medical team. Aims of the study: First, this study aimed to examine the maturation trajectory of post-burn HS in a 6-month monitored pressure therapy intervention programme to investigate the differences in the maturation process among patients received early intervention or late intervention; second, to explore the optimal timing of intervention and the mechanism of the effect of pressure on HS and to find evidence to support the combination of pressure therapy with other treatments. Methods: Thirty-four patients with 65 post-burn HS samples were recruited. All subjects underwent a 6-month pressure therapy programme, with the pressure dosage regulated with a newly developed pressure therapy system: Smart Pressure Monitored Suits. The scars were assessed with a MiniScan XE spectrocolorimeter for scar pigmentation and Terason t3000 portable ultrasound imaging equipment for scar thickness. The Vancouver Scar Scale (VSS) was also used to evaluate the scars' pigmentation, pliability, vascularity and height. The subjects' reports of pain and pruritus were documented. Assessments were conducted before treatment began and monthly during the 6-month intervention process. The patients were further divided into two groups according to the time of the intervention after their burn injuries to review differences in the maturation trajectory between those with early versus late treatment (the early intervention group was prescribed within 60 days after injury, and the late intervention group was prescribed in 61 to 183 days after injury). The changes in scar features were recorded to formulate the recovery trajectory of scars, and the outcomes of the intervention were compared between the early and late groups. Meanwhile, 12 scars were collected from patients with HS of similar age at homologous sites (mainly on the upper or lower limbs) who had never undergone pressure therapy during scar excision surgeries and were used as reference scars to compare with biopsy scar samples. The histopathological characteristics of all the HS tissues were studied, and comparisons were made between pre-treatment and post-treatment scars, between different intervention groups and between pressurised scar samples and non-pressurised scar samples. Results: A pre- and post-treatment comparison demonstrated significant improvement in scar pigmentation, thickness, VSS scores and pain and pruritus scores (p<0.01) in the early intervention group. In the late intervention group, only scar lightness, yellowness, VSS scores and pain and pruritus scores were found to show significant improvement (p<0.01). These improvements were sustained over time during the treatment process. The early group demonstrated a better effect in improving scar lightness, yellowness (p<0.01), thickness (p<0.01), pigmentation score (p<0.05) and pain score (p<0.01) than the late group at a similar time after burn injury. The expression of epidermal CK6 was downregulated after pressure therapy (p<0.01 in the early group, p>0.05 in the late group) and was significantly lower than that seen in the reference scars. The expression of CK6 in the pressurised scars was significantly lower than that in the non-pressurised scars (p<0.05). The expression of Ki67 was also downregulated after pressure therapy (p<0.05 in the early group and p>0.05 in the late group), with a significant time by group effect between the intervention groups. In the dermal layer of the HS tissue, the two intervention groups demonstrated similar trends regarding apoptosis (p>0.05). The expression of α-smooth muscle actin (α-SMA) was reduced after pressure therapy (p<0.05 in the early group and p>0.05 in the late group), and the pressurised scars in the late group showed greater expression of α-SMA than the non-pressurised scars in the reference group (p<0.05). The collagen fibrils in the HS tissue were realigned after pressure treatment, but their expression level was also higher than before (p>0.05 in the early group and p<0.05 in the late group). In the epidermal layer, the expression of transforming growth factor (TGF) β1 was upregulated after pressure therapy (p<0.05 in the late group), and it was lower in the pressurised scars than in the non-pressurised scars at 4.5 months (the early group scars after pressure therapy vs. the late group scar samples before pressure therapy) and 8 months (the late group scars after pressure therapy vs. the reference scars) after the initial injury (both p<0.05). Epidermal expression of TGFβ-RI, TGFβ-RII and pSmad2/3 was also increased. In the dermal layer, the expression of TGF-β1, TGFβ-RI and TGFβ-RII decreased after pressure therapy (p<0.05) in the early group but increased in the late group (p>0.05), whilst the expression of pSmad2/3 was downregulated in both groups, with a significant time by group effect (p<0.01). The expression of epidermal TGF-β1 showed a positive relationship with the epidermal expression of its receptors and with the dermal expression of TGF-β1 and related receptors (p<0.05). After pressure treatment, the change in the expression of epidermal TGFβ-RI was related to the change in the epidermal expression of TGFβ-RII and pSmad2/3, and it also affected the expression of Ki67; the change in the expression of dermal TGFβ- RI was related to those of TGFβ-RII and α-SMA. Conclusions: HS appeared to undergo continuous improvement in appearance and in pain and pruritus over time throughout the monitored pressure intervention programme. Early application of pressure therapy after burn injury may contribute to better outcomes, as shown by a faster recovery time in those with early intervention. To achieve the best outcomes, regular evaluation and adjustment is necessary to maintain the optimal interface pressure. Pressure seemed to change the activation and proliferation activity of keratinocytes and myofibroblasts in the scar tissue, and the TGF-β signalling pathway was found to be involved in this process. This involvement indicates the possibility that pressure therapy and other TGFβ-targeting therapies could be combined for the management of HS. |
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| Access: | open access |
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