Intravital microscopy evaluation of angiogenesis and its effects on glucose sensor performance.

Abstract

An optical window model for the rodent dorsum was used to perform chronic and quantitative intravital microscopy and laser Doppler flowmetry of microvascular networks adjacent to functional and non-functional glucose sensors. The one-sided configuration afforded direct, real-time observation of the tissue response to bare (unmodified, smooth surface) sensors and sensors coated with porous poly-L-lactic acid (PLLA). Microvessel length density and red blood cell flux (blood perfusion) within 1 mm of the sensors were measured bi-weekly over 2 weeks. When non-functional sensors were fully implanted beneath the windows, the porous coated sensors had two-fold more vasculature and significantly higher blood perfusion than bare sensors on Day 14. When functional sensors were implanted percutaneously, as in clinical use, no differences in baseline current, neovascularization, or tissue perfusion were observed between bare and porous coated sensors. However, percutaneously implanted bare sensors had two-fold more vascularity than fully implanted bare sensors by Day 14, indicating the other factors, such as micromotion, might be stimulating angiogenesis. Despite increased angiogenesis adjacent to percutaneous sensors, modest sensor current attenuation occurred over 14 days, suggesting that factors other than angiogenesis may play a dominant role in determining sensor function.