TY - JOUR
T1 - Mimicking fat grafting of fibrotic scars using 3D-organotypic skin cultures
AU - Raktoe, Rajiv
AU - Kwee, Anastasia K. A. L.
AU - Rietveld, Marion
AU - Marsidi, Nick
AU - Genders, Roel
AU - Quint, Koen
AU - van Doorn, Remco
AU - van Zuijlen, Paul
AU - Ghalbzouri, Abdoelwaheb E. L.
N1 - Funding Information: This project was funded by the Dutch Burn Foundation (Grant number: NO.14.105). Publisher Copyright: © 2023 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.
PY - 2023/10
Y1 - 2023/10
N2 - 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 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.
AB - 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 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.
KW - (hypertrophic) scars
KW - adipose tissue
KW - full-thickness model
KW - three-layered skin model
KW - tissue engineering
UR - http://www.scopus.com/inward/record.url?scp=85166419391&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/exd.14893
DO - https://doi.org/10.1111/exd.14893
M3 - Article
C2 - 37515391
SN - 0906-6705
VL - 32
SP - 1752
EP - 1762
JO - Experimental dermatology
JF - Experimental dermatology
IS - 10
ER -