title: Tensile forces stimulate vascular remodeling and epidermal cell proliferation in living skin.
abstract: OBJECTIVE
  To quantify tissue remodeling induced by static and cyclical application of tensional forces in a living perfused tissue.
  
  
  BACKGROUND
  Cells are able to respond to mechanical cues from the environment and can switch between proliferation and quiescence. However, the effects of different regimens of tension on living, perfused skin have not been characterized.
  
  
  METHODS
  The ears of living rats were mechanically loaded by applying tensile forces (0.5 Newtons) either statically or cyclically and then analyzing tissue responses using in vivo microscopy, immunohistochemistry, and corrosion casting.
  
  
  RESULTS
  Quantitative immunohistochemistry showed that in the static group (4-day continuous tension) there was up to 4-fold increase in cellular proliferation in the epidermis after 4 days and a 2.8-fold increase in the vascularity in the dermis that peaked after 2 days. Comparable effects could be achieved in just 8 hours using a cyclic loading protocol. We also modeled the resultant stress produced in the ear using a linear finite element model and demonstrated a correlation between the level of applied stress and both epidermal cell proliferation and blood vessel density.
  
  
  CONCLUSIONS
  Mechanical forces stimulate cell proliferation and vascular remodeling in living skin. As cell growth and vascular supply are critical to wound healing and tissue expansion, devices applying controlled mechanical loads to tissues may be a powerful therapy to treat tissue defects.
authors.affiliation: Tissue Engineering and Wound Healing Laboratory, Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pietramaggiori
authors.forename: Perry
authors.initials: P
authors.lastname: Liu
authors.forename: Saja S
authors.initials: SS
authors.lastname: Scherer
authors.forename: Arja
authors.initials: A
authors.lastname: Kaipainen
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Prsa
authors.forename: Horacio
authors.initials: H
authors.lastname: Mayer
authors.forename: Jennifer
authors.initials: J
authors.lastname: Newalder
authors.forename: Michael
authors.initials: M
authors.lastname: Alperovich
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Mentzer
authors.forename: Moritz A
authors.initials: MA
authors.lastname: Konerding
authors.forename: Sui
authors.initials: S
authors.lastname: Huang
authors.forename: Donald E
authors.initials: DE
authors.lastname: Ingber
authors.forename: Dennis P
authors.initials: DP
authors.lastname: Orgill
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004423:Ear; D004847:Epithelial Cells / Q000502:physiology; D020342:Finite Element Analysis; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology*; D013314:Stress, Mechanical; D013718:Tensile Strength; D015626:Tissue Expansion / Q000379:methods*