Consequences of seeded cell type on vascularization of tissue engineering constructs in vivo.
Implantation of tissue engineering constructs is a promising technique to reconstruct injured tissue. However, after implantation the nutrition of the constructs is predominantly restricted to vascularization. Since cells possess distinct angiogenic potency, we herein assessed whether scaffold vitalization with different cell types improves scaffold vascularization. 32 male balb/c mice received a dorsal skinfold chamber. Angiogenesis, microhemodynamics, leukocyte-endothelial cell interaction and microvascular permeability induced in the host tissue after implantation of either collagen coated poly (L-lactide-co-glycolide) (PLGA) scaffolds (group 4), additionally seeded with osteoblast-like cells (OLCs, group 1), bone marrow mesenchymal stem cells (bmMSCs, group 2) or a combination of OLCs and bmMSCs (group 3) were analyzed repetitively over 14 days using intravital fluorescence microscopy. Apart from a weak inflammatory response in all groups, vascularization was found distinctly accelerated in vitalized scaffolds, indicated by a significantly increased microvascular density (day 6, group 1: 202+/-15 cm/cm(2), group 2: 202+/-12 cm/cm(2), group 3: 194+/-8 cm/cm(2)), when compared with controls (group 4: 72+/-5 cm/cm(2)). This acceleration was independent from the seeded cell type. Immunohistochemistry revealed in vivo VEGF expression in close vicinity to the seeded OLCs and bmMSCs. Therefore, the observed lack of cell type confined differences in the vascularization process suggests that the accelerated vascularization of vitalized scaffolds is VEGF-related rather than dependent on the potential of bmMSCs to differentiate into specific vascular cells.
Schumann
Paul
P
Department of Oral and Maxillofacial Surgery, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany. schumann.paul@mh-hannover.de
Tavassol
Frank
F
Lindhorst
Daniel
D
Stuehmer
Constantin
C
Bormann
Kai-Hendrik
KH
Kampmann
Andreas
A
Mülhaupt
Rolf
R
Laschke
Matthias W
MW
Menger
Michael D
MD
Gellrich
Nils-Claudius
NC
Rücker
Martin
M
D000469:Alkaline Phosphatase / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002232:Carbocyanines / Q000378:metabolism; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D005269:Femur / Q000166:cytology; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes / Q000378:metabolism; D007150:Immunohistochemistry; D007211:Indoles / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D011100:Polyglycolic Acid / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013977:Tibia / Q000166:cytology; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
D001672:Biocompatible Materials; D002232:Carbocyanines; D005456:Fluorescent Dyes; D007211:Indoles; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C007293:DAPI; C011203:cyanine dye 2; D003094:Collagen; D000469:Alkaline Phosphatase