In burn patients, wound healing is often accompanied by hypertrophic scarring (HTS), resulting in both functional and aesthetic problems. HTSs are characterized by abundant presence of... Show moreIn burn patients, wound healing is often accompanied by hypertrophic scarring (HTS), resulting in both functional and aesthetic problems. HTSs are characterized by abundant presence of myofibroblasts (MFs) residing in the dermis. HTS development and MF persistence is primarily regulated by TGF-beta signalling. A promising method to target the transforming growth factor receptor I (TGF beta RI; also known as activin-like kinase 5 (ALK5)) is by making use of exon skipping through antisense oligonucleotides. In HTS the distinguishing border between the papillary dermis and the reticular dermis is completely abrogated, thus exhibiting a one layered dermis containing a heterogenous fibroblast population, consisting of papillary fibroblasts (PFs), reticular fibroblasts (RFs) and MFs. It has been proposed that PFs, as opposed to RFs, exhibit anti-fibrotic properties. Currently, it is still unclear which fibroblast subtype is most affected by exon skipping treatment.Therefore, the aim of this study was to investigate the effect of TGF beta RI inhibition by exon skipping in PF, RF and HTS fibroblast monocultures.Morphological analyses revealed the presence of a PF-like population after exon skipping in the different fibroblast cultures. This observation was further confirmed by the expression of genes specific for PFs, demonstrated by qPCR analyses. Further investigations on mRNA and protein level revealed that indeed MFs and to a lesser extent RFs are targeted by exon skipping. Furthermore, collagen gel contraction analysis showed that ALK5 exon skipping reduced TGF-beta-induced contraction together with decreased alpha-smooth muscle actin expression levels.In conclusion, we show for the first time that exon skipping primarily targets pro fibrotic fibroblasts. This could be a promising step towards reduced HTS development of burn tissue. (C) 2021 The Authors. Published by Elsevier Ltd. Show less
Raktoe, R.S.; Haasterecht, L. van; Antonovaite, N.; Bartolini, L.; Doorn, R. van; Zuijlen, P.P.M. van; ... ; Ghalbzouri, A.E. 2021
Objective: This study aimed to provide insight into the patterns and factors that predict burn scar outcomes at 3, 6 and 12 months after burn.Methods: The Patient and Observer Scar Assessment Scale... Show moreObjective: This study aimed to provide insight into the patterns and factors that predict burn scar outcomes at 3, 6 and 12 months after burn.Methods: The Patient and Observer Scar Assessment Scale (POSAS) was used to assess the scar formation of each patient. Structural equation modelling was used. The predictor variables used in this study were sex, three age categories, TBSA, depth of the wound and cause of the burn.Results: The POSAS patient total and individual item scores demonstrated a statistically significant decrease in the first 12 months after burn, except for the relief item. Male patients had a lower total and items scores (better scar quality) for pain and pruritus compared with female patients. Full thickness burns had a higher scores for pruritus, pliability, thickness and relief compared to the partial-thickness burns. Ages younger than 5 years, higher TBSA values and flame burns were predictors of various POSAS items at 3 and 6 months after burn.Conclusion: The POSAS patient total and individual item scores demonstrated a statistically significant improvement in the scar quality in the first 12 months after burn, except for the relief. Sex, age, depth of the wound, the percentage of TBSA and flame burns were predictors of various POSAS patient items at 3, 6 and 12 months after burn. (C) 2019 Elsevier Ltd and ISBI. All rights reserved. Show less
OBJECTIVE:This study aimed to provide insight into the patterns and factors that predict burn scar outcomes at 3, 6 and 12 months after burn.METHODS:The Patient and Observer Scar Assessment Scale ... Show moreOBJECTIVE:This study aimed to provide insight into the patterns and factors that predict burn scar outcomes at 3, 6 and 12 months after burn.METHODS:The Patient and Observer Scar Assessment Scale (POSAS) was used to assess the scar formation of each patient. Structural equation modelling was used. The predictor variables used in this study were sex, three age categories, TBSA, depth of the wound and cause of the burn.RESULTS:The POSAS patient total and individual item scores demonstrated a statistically significant decrease in the first 12 months after burn, except for the relief item. Male patients had a lower total and items scores (better scar quality) for pain and pruritus compared with female patients. Full thickness burns had a higher scores for pruritus, pliability, thickness and relief compared to the partial-thickness burns. Ages younger than 5 years, higher TBSA values and flame burns were predictors of various POSAS items at 3 and 6 months after burn.CONCLUSION:The POSAS patient total and individual item scores demonstrated a statistically significant improvement in the scar quality in the first 12 months after burn, except for the relief. Sex, age, depth of the wound, the percentage of TBSA and flame burns were predictors of various POSAS patient items at 3, 6 and 12 months after burn. Show less
