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Prevascularization of dermal substitutes with adipose tissue-derived microvascular fragments enhances early skin grafting


Frueh, Florian S; Später, Thomas; Körbel, Christina; Scheuer, Claudia; Simson, Anna C; Lindenblatt, Nicole; Giovanoli, Pietro; Menger, Michael D; Laschke, Matthias W (2018). Prevascularization of dermal substitutes with adipose tissue-derived microvascular fragments enhances early skin grafting. Scientific Reports, 8:10977.

Abstract

Split-thickness skin grafts (STSG) are still the gold standard for the treatment of most skin defects. Hence, there is an ongoing need to improve this procedure. For this purpose, we herein analyzed dermal matrices seeded with adipose tissue-derived microvascular fragments (ad-MVF) in a bradythrophic wound model. In additional experiments, the matrices were covered with autologous STSG 10 days after implantation. Green fluorescence protein (GFP) ad-MVF were isolated from C57BL/6-Tg(CAG-EGFP)1Osb/J mice and seeded onto collagen-glycosaminoglycan matrices. Non-seeded and prevascularized matrices were implanted into full-thickness skin defects on the skull of CD1 nu/nu mice for 21 days. Vascularization, lymphangiogenesis and incorporation of the matrices were analyzed using photo-acoustic imaging, trans-illumination stereomicroscopy, histology, and immunohistochemistry. The survival rate of STSG was assessed by planimetry. After 21 days, the density of microvascular and lymphatic networks was significantly higher in prevascularized matrices when compared to controls. This was associated with an improved implant integration. Moreover, prevascularization with ad-MVF allowed successful autologous skin grafting already at day 10, while coverage of non-seeded controls at day 10 resulted in STSG necrosis. In conclusion, ad-MVF represent powerful vascularization units. Seeded on dermal substitutes, they accelerate and enhance the healing of full-thickness skin defects and allow early coverage with STSG.

Abstract

Split-thickness skin grafts (STSG) are still the gold standard for the treatment of most skin defects. Hence, there is an ongoing need to improve this procedure. For this purpose, we herein analyzed dermal matrices seeded with adipose tissue-derived microvascular fragments (ad-MVF) in a bradythrophic wound model. In additional experiments, the matrices were covered with autologous STSG 10 days after implantation. Green fluorescence protein (GFP) ad-MVF were isolated from C57BL/6-Tg(CAG-EGFP)1Osb/J mice and seeded onto collagen-glycosaminoglycan matrices. Non-seeded and prevascularized matrices were implanted into full-thickness skin defects on the skull of CD1 nu/nu mice for 21 days. Vascularization, lymphangiogenesis and incorporation of the matrices were analyzed using photo-acoustic imaging, trans-illumination stereomicroscopy, histology, and immunohistochemistry. The survival rate of STSG was assessed by planimetry. After 21 days, the density of microvascular and lymphatic networks was significantly higher in prevascularized matrices when compared to controls. This was associated with an improved implant integration. Moreover, prevascularization with ad-MVF allowed successful autologous skin grafting already at day 10, while coverage of non-seeded controls at day 10 resulted in STSG necrosis. In conclusion, ad-MVF represent powerful vascularization units. Seeded on dermal substitutes, they accelerate and enhance the healing of full-thickness skin defects and allow early coverage with STSG.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Reconstructive Surgery
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:20 July 2018
Deposited On:11 Sep 2018 12:19
Last Modified:30 Sep 2018 23:59
Publisher:Nature Publishing Group
ISSN:2045-2322
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41598-018-29252-6
PubMed ID:30030486

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