title: Biomechanical regulation of blood vessel growth during tissue vascularization.
abstract: Formation of new vessels in granulation tissue during wound healing has been assumed to occur solely through sprouting angiogenesis. In contrast, we show here that neovascularization can be accomplished by nonangiogenic expansion of preexisting vessels. Using neovascularization models based on the chick chorioallantoic membrane and the healing mouse cornea, we found that tissue tension generated by activated fibroblasts or myofibroblasts during wound contraction mediated and directed translocation of the vasculature. These mechanical forces pulled vessels from the preexisting vascular bed as vascular loops with functional circulation that expanded as an integral part of the growing granulation tissue through vessel enlargement and elongation. Blockade of vascular endothelial growth factor receptor-2 confirmed that biomechanical forces were sufficient to mediate the initial vascular growth independently of endothelial sprouting or proliferation. The neovascular network was further remodeled by splitting, sprouting and regression of individual vessels. This model explains the rapid appearance of large functional vessels in granulation tissue during wound healing.
authors.affiliation: Department of Medical Biochemistry and Microbiology, Biomedical Center, University of Uppsala, Uppsala, Sweden.
authors.forename: Witold W
authors.initials: WW
authors.lastname: Kilarski
authors.forename: Branka
authors.initials: B
authors.lastname: Samolov
authors.forename: Ludvig
authors.initials: L
authors.lastname: Petersson
authors.forename: Anders
authors.initials: A
authors.lastname: Kvanta
authors.forename: Pär
authors.initials: P
authors.lastname: Gerwins
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002645:Chickens; D003094:Collagen / Q000378:metabolism; D003315:Cornea / Q000098:blood supply; D065306:Corneal Injuries; D005337:Fibrin / Q000378:metabolism; D051379:Mice; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D051381:Rats; D013997:Time Factors; D014945:Wound Healing
chemical_list: D005337:Fibrin; D003094:Collagen