IMPLANTABLE POLYMER SURFACES EXHIBITING REDUCED IN VIVO INFLAMMATORY RESPONSES
Embodiments of the invention provide optimized polymeric surfaces adapted for use with implantable medical devices as well as methods for making and using such polymeric surfaces. These polymer surfaces have a constellation of features that function to inhibit or avoid an inflammatory immune response generated by implantable medical devices. Typical embodiments of the invention include an implantable glucose sensor used in the management of diabetes having a polymer surface with the disclosed constellation of features.
1 . A medical device comprising a surface adapted to contact an in vivo environment, the surface comprising a polymer composition having the following characteristics:
a carbon-to-oxygen ratio of >5;
a surface hydrophobicity of between 75° and 90°;
a surface topography characterized by:
grooves having an average peak-to-valley height of between 0.3 μm and 5 μm;
wells having an average peak-to-valley height of between 1 μm and 2 μm; or
grids having an average peak-to-valley height of between 2 μm and 4 μm;
wherein:
when exposed to the surface comprising the polymer composition, RAW264.7 macrophages are influenced in a manner that inhibits their differentiation into an inflammatory (M1) phenotype, and/or influenced in a manner that facilitates their differentiation into an anti-inflammatory (M2) phenotype.
2 . The medical device of claim 1 , wherein the device is a glucose sensor.
3 . The medical device of claim 2 , wherein the glucose sensor comprises:
a base layer;
a working electrode, a reference electrode, and a counter electrode disposed on the base layer;
an analyte sensing layer disposed over the working electrode, wherein the analyte sensing layer comprises glucose oxidase; and
an analyte modulating layer disposed over the analyte sensing layer, wherein the analyte modulating layer modulates the diffusion of glucose therethrough.
4 . The medical device of claim 3 , wherein when exposed to the surface comprising the polymer composition, RAW264.7 macrophages exhibit a decrease in MIP-1α polypeptide expression of at least 10% as compared to an equivalent polymer surface not having a surface topography characterized by:
grooves having an average peak-to-valley height of between 0.3 μm and 5 μm;
wells having an average peak-to-valley height of between 1 μm and 2 μm; or
grids having an average peak-to-valley height of between 2 μm and 4 μm.
5 . The medical device of claim 4 , wherein when exposed to the surface comprising the polymer composition, RAW264.7 macrophages adherence to the surface is inhibited by at least 10% as compared to an equivalent polymer surface not having a surface topography characterized by:
grooves having an average peak-to-valley height of between 0.3 μm and 5 μm;
wells having an average peak-to-valley height of between 1 μm and 2 μm; or
grids having an average peak-to-valley height of between 2 μm and 4 μm.
6 . The medical device of claim 5 , wherein the polymer comprises a polyimide, a polyamide, a polyethylene terephthalate, a ethylene tetrafluoroethylene, a polyether block amide, a polycarbonate, a polypropylene, a polyethylene, a polystyrene, a polyvinyl chloride, a polymethyl methacrylate, an acrylonitrile butadiene, a polyetheretherketone, a polyurethane or an epoxy.
7 . The medical device of claim 1 , wherein the surface topography characterized by grids having an average peak-to-valley height of between 2 μm and 4 μm.
8 . The medical device of claim 1 , wherein the surface topography characterized by wells having an average peak-to-valley height of between 1 μm and 2 μm.
9 . The medical device of claim 1 , wherein the surface topography characterized by grooves having an average peak-to-valley height of between 0.3 μm and 5 μm.
10 . A method of avoiding and inflammatory response to an implanted medical device comprising implanting the device having a surface adapted to contact an in vivo environment, the surface comprising a polymer composition having the following characteristics:
a carbon-to-oxygen ratio of >5;
a surface hydrophobicity of between 75° and 90°;
a surface topography characterized by:
grooves having an average peak-to-valley height of between 0.3 μm and 5 μm;
wells having an average peak-to-valley height of between 1 μm and 2 μm; or
grids having an average peak-to-valley height of between 2 μm and 4 μm;
wherein:
the surface avoids an inflammatory response by having surface characteristics such that when exposed to the surface comprising the polymer composition, RAW264.7 macrophages are influenced to differentiate into an anti-inflammatory (M2) phenotype.
11 . The method of claim 10 , wherein the medical device is implanted in an interstitial space.
12 . The method of claim 10 , wherein the medical device is a glucose sensor.
13 . The method of claim 10 , wherein the polymer comprises a polyimide, a polyamide, a polyethylene terephthalate, a ethylene tetrafluoroethylene, a polyether block amide, a polycarbonate, a polypropylene, a polyethylene, a polystyrene, a polyvinyl chloride, a polymethyl methacrylate, an acrylonitrile butadiene, a polyetheretherketone, a polyurethane or an epoxy.
14 . The method of claim 10 , wherein when exposed to the surface comprising the polymer composition, RAW264.7 macrophages:
exhibit a decrease in MIP-1α polypeptide expression of at 10%; and
exhibit a decrease in adherence to the surface of at least 10%;
as compared to an equivalent polymer surface not having a surface topography characterized by:
grooves having an average peak-to-valley height of between 0.3 μm and 5 μm;
wells having an average peak-to-valley height of between 1 μm and 2 μm; or
grids having an average peak-to-valley height of between 2 μm and 4 μm.
15 . A polymer composition that forms a surface comprising:
a carbon-to-oxygen ratio of >5;
a surface hydrophobicity of between 75° and 90°;
a surface topography characterized by:
grooves having an average peak-to-valley height of between 0.3 μm and 5 μm;
wells having an average peak-to-valley height of between 1 μm and 2 μm; or
grids having an average peak-to-valley height of between 2 μm and 4 μm; wherein:
when exposed to the surface, RAW264.7 macrophages are influenced to differentiate into an anti-inflammatory (M2) phenotype.