title: Functionalization of matrices by cyclically stretched osteoblasts through matrix targeting of VEGF.
abstract: Vascular endothelial growth factor A (VEGF) plays a central role in load-induced bone gain. We previously showed that increasing cyclic stretch frequency from 0.05 to 5 Hz induce parallel increased in entrapment of VEGF (mVEGF) into osteoblast secreted extracellular matrix. We ask in this study if mVEGF could be protective against apoptotic signals and biologically active in vitro on endothelial cell migration as well as in vivo on angiogenesis. We established that mechanically-induced VEGF entrapment using stretched silicone membrane was saturable after 3 exposures at high frequency stretches (5Hz). We found that mVEGF stimulates microvascular cells migration and enhanced angiogenesis more importantly than VEGF 165 controls suggesting the absence of potent anti-angiogenic factors in our functionalized matrices. Indeed we found that the anti-angiogenic factors, tissue inhibitor of metalloproteinase (TIMP2) and pigment epithelium-derived factor (PEDF) were specifically downregulated for 5 Hz stretch and that the release of these potent factors was increased for low frequency of stretch (0.05 Hz). This study qualifies high frequency cyclic stretch as an interesting approach for surfaces activation of deformable biomaterials.
authors.affiliation: INSERM U890, St Etienne F42023, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Faure
authors.forename: Laurence
authors.initials: L
authors.lastname: Vico
authors.forename: Philippe
authors.initials: P
authors.lastname: Tracqui
authors.forename: Norbert
authors.initials: N
authors.lastname: Laroche
authors.forename: Arnaud
authors.initials: A
authors.lastname: Vanden-Bossche
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Linossier
authors.forename: Aline
authors.initials: A
authors.lastname: Rattner
authors.forename: Alain
authors.initials: A
authors.lastname: Guignandon
mesh_terms: D000818:Animals; D017209:Apoptosis; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D002478:Cells, Cultured; D002648:Child; D015536:Down-Regulation; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics; D006801:Humans; D055595:Mechanical Phenomena; D051379:Mice; D008819:Mice, Nude; D018919:Neovascularization, Physiologic; D009414:Nerve Growth Factors / Q000235:genetics; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D015843:Serpins / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D001672:Biocompatible Materials; D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D019716:Tissue Inhibitor of Metalloproteinase-2; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor