title: Adipose Tissue-Derived Microvascular Fragments Improve Vascularization, Lymphangiogenesis, and Integration of Dermal Skin Substitutes.
abstract: Full-thickness skin defects can be covered with dermal skin substitutes in combination with split-thickness skin grafts. However, slow vascularization of the matrices bears the risk of wound infection and extends the length of hospitalization. To overcome these problems, we describe a promising vascularization strategy. Green fluorescent protein+adipose tissue-derived microvascular fragments (ad-MVF) were isolated from epididymal fat pads of C57BL/6-Tg(CAG-EGFP)1Osb/J mice. ad-MVF were seeded on collagen-glycosaminoglycan matrices, which were implanted into full-thickness skin defects in the dorsal skinfold chamber of wild-type C57BL/6 mice. Nonseeded matrices served as controls. Vascularization, lymphangiogenesis, and integration of the implants were studied by using intravital fluorescence microscopy, histology, and immunohistochemistry over 14 days. ad-MVF rapidly reassembled into microvascular networks within the implants, which developed interconnections to the host microvasculature. Accordingly, vascularization of the implants was markedly accelerated, as indicated by a significantly higher microvessel density when compared with controls. Moreover, dense lymphatic networks originating from the green fluorescent protein+ad-MVF developed within the implants. This was associated with an improved implant integration. Hence, seeding ad-MVF on collagen-glycosaminoglycan matrices represents a potential strategy to reduce morbidity and hospitalization of patients undergoing the treatment of full-thickness skin defects.
authors: Institute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg/Saar, Germany; Division of Plastic Surgery and Hand Surgery, University Hospital Zurich, 8091 Zurich, Switzerland. Electronic address: florian.frueh@uks.eu.
authors: Florian S
authors: FS
authors: Frueh
authors: Institute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg/Saar, Germany.
authors: Thomas
authors: T
authors: Später
authors: Division of Plastic Surgery and Hand Surgery, University Hospital Zurich, 8091 Zurich, Switzerland.
authors: Nicole
authors: N
authors: Lindenblatt
authors: Division of Plastic Surgery and Hand Surgery, University Hospital Zurich, 8091 Zurich, Switzerland.
authors: Maurizio
authors: M
authors: Calcagni
authors: Division of Plastic Surgery and Hand Surgery, University Hospital Zurich, 8091 Zurich, Switzerland.
authors: Pietro
authors: P
authors: Giovanoli
authors: Institute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg/Saar, Germany.
authors: Claudia
authors: C
authors: Scheuer
authors: Institute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg/Saar, Germany.
authors: Michael D
authors: MD
authors: Menger
authors: Institute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg/Saar, Germany.
authors: Matthias W
authors: MW
authors: Laschke
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D004195:Disease Models, Animal; D006085:Graft Survival; D048091:Guided Tissue Regeneration; D042583:Lymphangiogenesis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000254:growth & development*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011897:Random Allocation; D016038:Skin Transplantation / Q000009:adverse effects / Q000379:methods; D017768:Skin, Artificial; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds