Vascularizing the tissue surrounding a model biosensor: how localized is the effect of a subcutaneous infusion of vascular endothelial growth factor (VEGF)?
Implantable continuous biosensors would improve disease management but long term function of such devices have been limited by a hypovascular foreign body capsule that inhibits influx of analytes. To assess whether capsule vascularity could be increased, we studied the histologic effects of a 28-day continuous infusion of vascular endothelial growth factor (VEGF) (0.45 microg/day) vs. saline from the surface of a model disk biosensor that was implanted subcutaneously in rats. At day 40, tissue was obtained at varying distances from the infusion port and capsular microvessels were counted using two histologic techniques. VEGF treatment led to a marked increase in capillary density. In tissue located 1 mm away from the infusion site, capillary density in VEGF-treated animals was 200-300% higher than in saline controls. Tissue located 13 mm away, but not 25 mm away, also demonstrated neovascularization. Serum obtained from a distant vein during the infusion did not show an elevated concentration of VEGF. These data demonstrate that a subcutaneous infusion of VEGF creates localized neovascularization of the foreign body capsule and suggest that systemic effects of VEGF are avoidable. Vascularization of a foreign body capsule surrounding a subcutaneous biosensor might well extend its useful life.
Ward
W Kenneth
WK
Legacy Health System, Legacy Clinical Research and Technology Center, 1225 NE 2nd Avenue, Portland, OR 97232, USA. wkward@lhs.org
Quinn
Matthew J
MJ
Wood
Michael D
MD
Tiekotter
Kenneth L
KL
Pidikiti
Sudha
S
Gallagher
Jennifer A
JA
D000818:Animals; D015374:Biosensing Techniques / Q000295:instrumentation*; D004868:Equipment Failure; D019544:Equipment Failure Analysis / Q000379:methods*; D005549:Foreign-Body Reaction / Q000473:pathology* / Q000517:prevention & control*; D015918:Infusion Pumps, Implantable; D007263:Infusions, Parenteral; D008297:Male; D009389:Neovascularization, Pathologic / Q000139:chemically induced*; D019736:Prostheses and Implants / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*; D014945:Wound Healing / Q000187:drug effects*
D042461:Vascular Endothelial Growth Factor A