PMID- 37082911
OWN - NLM
STAT- MEDLINE
DCOM- 20230529
LR  - 20230609
IS  - 1530-8022 (Electronic)
IS  - 0885-3282 (Print)
IS  - 0885-3282 (Linking)
VI  - 37
IP  - 10
DP  - 2023 May
TI  - The use of commercial fibrin glue in dermal replacement material reduces 
      angiogenic and lymphangiogenic gene and protein expression in vitro.
PG  - 1858-1873
LID - 10.1177/08853282231171681 [doi]
AB  - BACKGROUND: Commercial fibrin glue is increasingly finding its way into clinical 
      practice in surgeries to seal anastomosis, and initiate hemostasis or tissue 
      repair. Human biological glue is also being discussed as a possible cell carrier. 
      To date, there are only a few studies addressing the effects of fibrin glue on 
      the cell-molecular level. This study examines the effects of fibrin glue on 
      angiogenesis and lymphangiogenesis, as well as adipose-derived stem cells (ASCs) 
      with a focus on gene and protein expression in scaffolds regularly used for 
      tissue engineering approaches. METHODS: Collagen-based dermal regeneration 
      matrices (DRM) were seeded with human umbilical vein endothelial cells (HUVEC), 
      human dermal lymphatic endothelial cells (LECs), or adipose-derived stem cells 
      (ASC) and fixed with or without fibrin glue according to the experimental group. 
      Cultures were maintained for 1 and 7 days. Finally, angiogenic and 
      lymphangiogenic gene and protein expression were measured with special regard to 
      subtypes of vascular endothelial growth factor (VEGF) and corresponding receptors 
      using Multiplex-qPCR and ELISA assays. In addition, the hypoxia-induced factor 
      1-alpha (HIF1a) mediated intracellular signaling pathways were included in 
      assessments to analyze a hypoxic encapsulating effect of fibrin polymers. 
      RESULTS: All cell types reacted to fibrin glue application with an alteration of 
      gene and protein expression. In particular, vascular endothelial growth factor A 
      (VEGFA), vascular endothelial growth factor B (VEGFB), vascular endothelial 
      growth factor C (VEGFC), vascular endothelial growth receptor 1 (VEGFR1/FLT1), 
      vascular endothelial growth receptor 2 (VEGFR2/KDR), vascular endothelial growth 
      receptor 3 (VEGFR3/FLT4) and Prospero Homeobox 1 (PROX1) were depressed 
      significantly depending on fibrin glue. Especially short-term fibrin effect led 
      to a continuous downregulation of respective gene and protein expression in 
      HUVECs, LECs, and ASCs. CONCLUSION: Our findings demonstrate the impact of fibrin 
      glue application in dermal regeneration with special regard to angiogenesis and 
      lymphangiogenesis. In particular, a short fibrin treatment of 24 hours led to a 
      decrease in gene and protein levels of LECS, HUVECs, and ASCs. In contrast, the 
      long-term application showed less effect on gene and protein expressions. 
      Therefore, this work demonstrated the negative effects of fibrin-treated cells in 
      tissue engineering approaches and could affect wound healing during dermal 
      regeneration.
FAU - Fuchs, Benedikt
AU  - Fuchs B
AUID- ORCID: 0000-0002-4539-6796
AD  - Department of Hand, Plastic and Aesthetic Surgery, LMU, Munich, Germany.
FAU - Birt, Alexandra
AU  - Birt A
AD  - Department of Hand, Plastic and Aesthetic Surgery, LMU, Munich, Germany.
FAU - Moellhoff, Nicholas
AU  - Moellhoff N
AD  - Department of Hand, Plastic and Aesthetic Surgery, LMU, Munich, Germany.
FAU - Kuhlmann, Constanze
AU  - Kuhlmann C
AD  - Department of Hand, Plastic and Aesthetic Surgery, LMU, Munich, Germany.
FAU - Giunta, Riccardo
AU  - Giunta R
AD  - Department of Hand, Plastic and Aesthetic Surgery, LMU, Munich, Germany.
FAU - Wiggenhauser, Paul Severin
AU  - Wiggenhauser PS
AD  - Department of Hand, Plastic and Aesthetic Surgery, LMU, Munich, Germany.
LA  - eng
PT  - Journal Article
DEP - 20230421
PL  - England
TA  - J Biomater Appl
JT  - Journal of biomaterials applications
JID - 8813912
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factor B)
RN  - 0 (Fibrin Tissue Adhesive)
RN  - 0 (Vascular Endothelial Growth Factor C)
SB  - IM
MH  - Humans
MH  - *Vascular Endothelial Growth Factor A/metabolism
MH  - *Lymphangiogenesis/genetics
MH  - Vascular Endothelial Growth Factor B/metabolism
MH  - Fibrin Tissue Adhesive/pharmacology/metabolism
MH  - Vascular Endothelial Growth Factor C/metabolism
MH  - Human Umbilical Vein Endothelial Cells/metabolism
PMC - PMC10226008
OTO - NOTNLM
OT  - Adipose-derived stem cells
OT  - Enzym-linked Immunosorbent Assay
OT  - Fibrin glue
OT  - Hypoxia-inducible factor 1-alpha
OT  - Lymphatic endothelial cells
OT  - Multiplex-RT-PCR
OT  - Vascular Endothelial Growth Factor
OT  - angiogenesis
OT  - gene and protein expression
OT  - human umbilical vein endothelial cells
OT  - lymphangiogenesis
COIS- The author(s) declared no potential conflicts of interest with respect to the 
      research, authorship, and/or publication of this article.
EDAT- 2023/04/21 06:41
MHDA- 2023/05/29 06:41
PMCR- 2023/05/29
CRDT- 2023/04/21 04:22
PHST- 2023/05/29 06:41 [medline]
PHST- 2023/04/21 06:41 [pubmed]
PHST- 2023/04/21 04:22 [entrez]
PHST- 2023/05/29 00:00 [pmc-release]
AID - 10.1177_08853282231171681 [pii]
AID - 10.1177/08853282231171681 [doi]
PST - ppublish
SO  - J Biomater Appl. 2023 May;37(10):1858-1873. doi: 10.1177/08853282231171681. Epub 
      2023 Apr 21.