Wound healing of deep burn injuries is often accompanied by severe scarring, such as hypertrophic scar (HTS) formation. In severe burn wounds, where the subcutis is also damaged, the scars adhere... Show moreWound healing of deep burn injuries is often accompanied by severe scarring, such as hypertrophic scar (HTS) formation. In severe burn wounds, where the subcutis is also damaged, the scars adhere to structures underneath, resulting in stiffness of the scar and impaired motion. Over the recent years, a promising solution has emerged: autologous fat grafting, also known as lipofilling. Previous clinical reports have shown that the anti-fibrotic effect has been attributed to the presence of adipose-derived stromal cells (ADSC). In the proposed study, we aim to investigate the effect of fat grafting in 3D organotypic skin cultures mimicking an HTS-like environment. To this end, organotypic skin cultures were embedded with normal skin fibroblasts (NF) or HTS-derived fibroblasts with or without incorporation of human adipose subcutaneous tissue (ADT) and one part was thermally wounded to examine their effect on epithelialization. The developed skin cultures were analysed on morphology and protein level. Analysis revealed that ADT-containing organotypic skin cultures comprise an improved epidermal homeostasis, and a fully formed basement membrane, similar to native human skin (NHS). Furthermore, the addition of ADT significantly reduced myofibroblast presence, which indicates its anti-fibrotic effect. Finally, re-epithelialization measurements showed that ADT reduced re-epithelialization in skin cultures embedded with NFs, whereas HTS-fibroblast-embedded skin cultures showed complete wound closure. In conclusion, we succeeded in developing a 3D organotypic HTS-skin model incorporated with subcutaneous tissue that allows further investigation on the molecular mechanism of fat grafting. Show less
Wound healing of deep burn injuries is often accompanied with severe scarring, such as hypertrophic scar (HTS) formation. In severe burn wounds, where the subcutis is also damaged, the scars adhere... Show moreWound healing of deep burn injuries is often accompanied with severe scarring, such as hypertrophic scar (HTS) formation. In severe burn wounds, where the subcutis is also damaged, the scars adhere to structures underneath, resulting in stiffness of the scar and impaired motion. Over the recent years, a promising solution has emerged: autologous fat grafting, also known as lipofilling. Previous clinical reports have shown that the antifibrotic effect has been attributed due to the presence of adipose-derived stromal cells (ADSC).In the proposed study we aim to investigate the effect of fat grafting in 3D organotypic skin cultures mimicking an HTS-like environment. To this end, organotypic skin cultures were embedded with normal skin fibroblasts (NF) or HTS-derived fibroblasts with or without incorporation of human adipose subcutaneous tissue (ADT) and one part was thermally wounded to examine their effect on epithelialisation. The developed skin cultures were analysed on morphology and protein level.Analysis revealed that ADT-containing organotypic skin cultures comprise an improved epidermal homeostasis, and a fully formed basement membrane, similar to native human skin (NHS). Furthermore, addition of ADT significantly reduced myofibroblast presence, which indicates its anti-fibrotic effect. Finally, re-epithelialization measurements showed that ADT reduced re-epithelialization in skin cultures embedded with NFs, whereas HTS-fibroblast-embedded skin cultures showed complete wound closure. In conclusion, we succeeded in developing a 3D organotypic HTS-skin model incorporated with subcutaneous tissue that allows further investigation on the molecular mechanism of fat grafting. Show less
Gomez-Tomas, A.; Bouwes Bavinck, J.N.; Genders, R.; Gonzalez-Cruz, C.; Jong, E. de; Arron, S.; ... ; Ferrandiz-Pulido, C. 2022
Key Points Question: Is the Skin and UV Neoplasia Transplant Risk Assessment Calculator (SUNTRAC) tool valid for guiding skin cancer screening in solid organ transplant recipients (SOTRs)? Findings... Show moreKey Points Question: Is the Skin and UV Neoplasia Transplant Risk Assessment Calculator (SUNTRAC) tool valid for guiding skin cancer screening in solid organ transplant recipients (SOTRs)? Findings: This prognostic study found good prognostic discrimination in a European cohort of 3421 SOTRs. The observed skin cancer incidences were similar to those predicted from the US SOTR population for each risk group. Meaning: These findings suggest that the SUNTRAC tool can be transported to different populations to stratify SOTRs into distinct skin cancer risk groups and identify those at a very high risk, opening the door to efficient and effective preventive measures.This prognostic study assesses the Skin and UV Neoplasia Transplant Risk Assessment Calculator (SUNTRAC) tool to validate it in different populations of solid organ transplant recipients.Importance: The Skin and UV Neoplasia Transplant Risk Assessment Calculator (SUNTRAC) tool has been developed in the US to facilitate the identification of solid organ transplant recipients (SOTRs) at a higher risk of developing skin cancer. However, it has not yet been validated in populations other than the one used for its creation. Objective: To provide an external validation of the SUNTRAC tool in different SOTR populations. Design, Setting, and Participants: This retrospective external validation prognostic study used data from a prospectively collected cohort of European SOTRs from transplant centers at teaching hospitals in the Netherlands (1995-2016) and Spain (2011-2021). Participants were screened and followed up at dermatology departments. Data were analyzed from September to October 2021. Main Outcomes and Measures: The discrimination ability of the SUNTRAC tool was assessed via a competing risk survival analysis, cumulative incidence plots, and Wolbers concordance index. Calibration of the SUNTRAC tool was assessed through comparison of projected skin cancer incidences. Skin cancer diagnoses included squamous cell carcinoma, basal cell carcinoma, melanoma, and Merkel cell carcinoma. Results: A total of 3421 SOTRs (median age at transplant, 53 [quartile 1: 42; quartile 3: 62] years; 2132 [62.3%] men) were assessed, including 72 Asian patients (2.1%), 137 Black patients (4.0%), 275 Latinx patients (8.0%), 109 Middle Eastern and North African patients (3.2%), and 2828 White patients (82.7%). With a total of 23213 years of follow-up time, 603 patients developed skin cancer. The SUNTRAC tool classified patients into 4 groups with significantly different risks of developing skin cancer during follow-up. Overall, the relative rate for developing skin cancer estimated using subdistribution hazard ratios (SHRs) and using the low-risk group as the reference group, increased according to the proposed risk group (medium-risk group: SHR, 6.8 [95% CI, 3.8-12.1]; P<.001; high-risk group: SHR, 15.9 [95% CI, 8.9-28.4]; P<.001; very-high-risk group: SHR, 54.8 [95% CI, 29.1-102.9]; P<.001), with a concordance index of 0.72. Actual skin cancer incidences were similar to those predicted by the SUNTRAC tool (5-year skin cancer cumulative incidence for medium-risk group: predicted, 6.2%; observed, 7.0%). Conclusions and Relevance: The findings of this external validation prognostic study support the use of the SUNTRAC tool in European populations for stratifying SOTRs based on their skin cancer risk and also detecting patients at a high risk of developing skin cancer. This can be helpful in prioritizing and providing better screening and surveillance for these patients. Show less
