| dc.description.abstract |
<p>Efforts to create a reliable, long–term implantable glucose sensor have been stymied
by the effects of the foreign body response and wound healing that introduce delayed
response times as well as unpredictable sensor performance. Loss of vascularization
from fibrotic encapsulation around implanted sensors is purported as a key contributor
to sensor failure, as glucose and oxygen transport to the sensor becomes impeded.
Improving sensor performance by increasing angiogenesis and/or reducing capsule thickness
using tissue-modifying textured coatings is attractive because texturing is not dependent
upon a depletable drug reservoir. A significant range of materials and pore sizes
are capable of promoting angiogenesis and reducing capsule thickness, provided pores
have open-architecture with dimensions sufficiently large enough to allow inflammatory
cell infiltration. </p><p><br></p><p>Poly–L–lactic acid was gas foamed/salt leached
with ammonium bicarbonate to produce porous coatings for Medtronic MiniMed SOF–sensor
glucose sensors. Coating properties included 30μm pore diameters, 90% porosity, and
50μm wall thickness. Cytotoxicity, degradation, and sensor response time studies
were performed to ensure the porous coatings were non–toxic and negligibly retarded
glucose diffusion prior to <italic>in vivo</italic> testing. Histology was used
to evaluate angiogenesis and collagen deposition adjacent to porous coated and bare
(i.e. smooth, uncoated) non–functional sensor strips after three weeks in the rat
dorsal subcutis. Functional Medtronic glucose sensors, with and without porous coatings,
were percutaneously implanted in the rat dorsum to assess if the angiogenic–inducing
properties observed around the non–functional porous coated sensor strips translated
into stable, non–attenuated sensor signals over two and three weeks. MiniLink<super>TM
</super>transmitters were attached to the rats, permitting continuous glucose monitoring.
Vessel counts and collagen deposition adjacent to sensors were determined from histological
analysis. A one–sided dorsal window model was developed to further evaluate the interplay
between vascularization and sensor performance Sensors were inserted beneath the
windows, allowing visualization of microvascular changes adjacent to sensor surfaces,
with simultaneous evaluation of how vascular changes impacted interstitial glucose
monitoring. </p><p><br></p><p>Porous coating did have angiogenic–inducing effects
on the surrounding tissue. When fully implanted in the rat dorsum, sensor strips
with porous coatings induced three–fold more vessels within 100μm<super>2</super>
of the sensor strip surface after three weeks and two-fold more cumulative vessel
lengths within 1mm<super>2</super> after two weeks, compared to bare surfaces. In
contrast, when percutaneously implanted in the rat dorsum, porous coated and bare
sensors were equally highly vascularized, with two–fold more vessels than fully implanted
bare sensors. </p><p><br></p><p>Despite increased angiogenesis adjacent to percutaneous
sensors, sensor signal attenuation occurred over 14 days, suggesting that angiogenesis
plays a secondary role in maintaining sensor function. Percutaneously implanted porous
coated sensors had greater reductions in baseline current (20 to 50+%) over two weeks
than bare sensors (10 to 30%). Mechanical stresses imposed by percutaneous tethering
may override the beneficial effects of porous coatings. Furthermore, integration
of the porous coating with the surrounding tissue may have increased tissue tearing
at the porous coating–tissue, increasing inflammation and collagen deposition resulting
in greater signal attenuation compared with bare sensors. Future investigations
of the role mechanical irritation has on wound healing around percutaneous glucose
sensors are warranted.</p>
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