title: Tissue engineered pre-vascularized buccal mucosa equivalents utilizing a primary triculture of epithelial cells, endothelial cells and fibroblasts.
abstract: Artificial generated buccal mucosa equivalents are a promising approach for the reconstruction of urethral defects. Limiting in this approach is a poor blood vessel supply after transplantation, resulting in increased morbidity and necrosis. We generated a pre-vascularized buccal mucosa equivalent in a tri-culture of primary buccal epithelial cells, fibroblasts and microvascular endothelial cells, using a native collagen membrane as a scaffold. A successful pre-vascularization and dense formation of capillary-like structures at superficial areas was demonstrated. The lumen size of pre-formed blood vessels corresponded to the capillary size in vivo (10-30 μm). Comparing native with a highly cross-linked collagen membrane we found a distinct higher formation of capillary-like structures on the native membrane, apparently caused by higher secretion of angiogenic factors such as PDGF, IL-8 and angiopoietin by the cells. These capillary-like structures became functional blood vessels through anastomosis with the host vasculature after implantation in nude mice. This in vitro method should result in an accelerated blood supply to the biomaterial with cells after transplantation and increase the succes rates of the implant material.
authors.affiliation: Department of Urology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany; Department of Otorhinolaryngology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany; For BiomaTiCS - Biomaterials, Tissues and Cells in Science, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Heller
authors.affiliation: Department of Urology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany; For BiomaTiCS - Biomaterials, Tissues and Cells in Science, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
authors.forename: E V
authors.initials: EV
authors.lastname: Frerick-Ochs
authors.affiliation: Department of Urology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany; For BiomaTiCS - Biomaterials, Tissues and Cells in Science, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
authors.forename: H-K
authors.initials: HK
authors.lastname: Bauer
authors.affiliation: Department of Maxillofacial Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany; For BiomaTiCS - Biomaterials, Tissues and Cells in Science, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Schiegnitz
authors.affiliation: Department of Urology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany; For BiomaTiCS - Biomaterials, Tissues and Cells in Science, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Flesch
authors.affiliation: Department of Otorhinolaryngology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany; For BiomaTiCS - Biomaterials, Tissues and Cells in Science, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Brieger
authors.affiliation: Department of Urology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Stein
authors.affiliation: Department of Maxillofacial Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany; For BiomaTiCS - Biomaterials, Tissues and Cells in Science, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Al-Nawas
authors.affiliation: Department of Pathology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany; For BiomaTiCS - Biomaterials, Tissues and Cells in Science, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Brochhausen
authors.affiliation: Department of Urology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
authors.forename: J W
authors.initials: JW
authors.lastname: Thüroff
authors.affiliation: Department of Pathology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany; For BiomaTiCS - Biomaterials, Tissues and Cells in Science, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
authors.forename: R E
authors.initials: RE
authors.lastname: Unger
authors.affiliation: Department of Urology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany; For BiomaTiCS - Biomaterials, Tissues and Cells in Science, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany. Electronic address: brenner@uni-mainz.de.
authors.forename: W
authors.initials: W
authors.lastname: Brenner
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000032:analysis; D000818:Animals; D002196:Capillaries / Q000166:cytology / Q000254:growth & development; D002478:Cells, Cultured; D018920:Coculture Techniques; D003094:Collagen; D042783:Endothelial Cells / Q000166:cytology*; D004847:Epithelial Cells / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology*; D052816:Foreskin / Q000166:cytology; D005881:Gingiva / Q000166:cytology; D064593:Heterografts; D006801:Humans; D008297:Male; D008567:Membranes, Artificial; D051379:Mice; D008819:Mice, Nude; D009061:Mouth Mucosa; D009940:Organoids / Q000098:blood supply* / Q000166:cytology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D019737:Transplants / Q000098:blood supply*
chemical_list: D043925:Angiogenesis Inducing Agents; D008567:Membranes, Artificial; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D003094:Collagen
keywords: Buccal mucosa equivalent; Epithelial cells; Fibroblasts; Microvascular endothelial cells; Pre-vascularization; Tri-culture