Surface Topographies for Altering the Physiology of Living Cells

Abstract

An object for altering cell behavior includes a surface part provided with at least one topography configured to modulate at least one of morphology, proliferation, biochemical functioning, differentiation, attachment, migration, signaling, or cell death of a cell population by physical stimulation, where the at least one topography includes a surface and multiple protrusions protruding from the surface, where the protrusions define multiple valleys between adjacent protrusions such that the adjacent protrusions do not touch, where each protrusion includes at least one protrusion element, where the top surface area of the at least one protrusion element has a complex shape comprising a combination of basic shapes, interconnected by one or more overlapping portions, the basic shapes including at least one of a circle, oval, triangle, square, rectangle, trapezoid, pentagon, hexagon, heptagon or octagon.

1 . An object for altering cell behavior, the object comprising:
 a surface part provided with at least one topography configured to modulate at least one of morphology, proliferation, biochemical functioning, differentiation, attachment, migration, signaling, or cell death of a cell population by physical stimulation,   wherein the at least one topography comprises a surface and a plurality of protrusions protruding from the surface, wherein the plurality of protrusions are individually spaced and arranged in a regular pattern,   wherein the plurality of protrusions define a plurality of valleys between adjacent protrusions of the plurality of protrusions, such that the adjacent protrusions do not touch,   wherein each protrusion of the plurality of protrusions comprises at least one protrusion element, wherein the at least one protrusion element comprises a surface portion which is elevated above the surface and which has a top surface area and a circumferential side face connecting the top surface area with the surface, and   wherein the top surface area of the at least one protrusion element of each protrusion has a complex shape comprising a combination of basic shapes, interconnected by one or more overlapping portions, the basic shapes comprising at least one of a circle, oval, triangle, square, rectangle, trapezoid, pentagon, hexagon, heptagon or octagon.   
     
     
         2 . The object of  claim 1 , wherein the at least one protrusion element of each protrusion has a maximum height of between 0.5 and 50 μm above the surface. 
     
     
         3 . The object of  claim 1 , wherein an average distance between the adjacent protrusions is between 0.5 and 50 μm. 
     
     
         4 . The object of  claim 1 , wherein the top surface area of the at least one protrusion element of each protrusion is between 1 and 6000 μm 2 . 
     
     
         5 . The object of  claim 1 , wherein the plurality of protrusions cover between 3% and 90% of the surface. 
     
     
         6 . The object of  claim 1 , wherein the surface part is formed from at least one of a metal material, a polymeric material, a ceramic material or a composite material. 
     
     
         7 . The object of  claim 1 , wherein the regular pattern of the plurality of protrusions is defined by a grid of intersecting gridlines laid over the surface, wherein the intersecting gridlines define unit cells, wherein each unit cell comprises a maximum of one protrusion. 
     
     
         8 . The object of  claim 1 , wherein the at least one topography is defined by:
 an average distance between the adjacent protrusions of 2-25 μm;   the top surface area of the at least one protrusion element between 30 μm 2  and 750 μm 2 ; and   the plurality of protrusions covering between 30% and 65% of the surface.   
     
     
         9 . The object of  claim 1 , wherein the at least one topography is defined by:
 an average distance between the adjacent protrusions of 3-25 μm;   the top surface area of the at least one protrusion element between 20 μm 2  and 250 μm 2 ; and   the plurality of protrusions covering between 8% and 35% of the surface.   
     
     
         10 . The object of  claim 1 , wherein the at least one topography is defined by:
 an average distance between the adjacent protrusions of 12.5-20 μm;   the top surface area of the at least one protrusion element between 25 μm 2  and 65 μm 2 ; and   the plurality of protrusions covering between 5% and 10% of the surface.   
     
     
         11 . The object of  claim 1 , wherein the at least one topography is configured for modulating the at least one of morphology, proliferation, biochemical functioning, differentiation, attachment, migration, signaling or cell death of the cell population by physical stimulation in vitro. 
     
     
         12 . The object of  claim 11 , wherein the modulation comprises maintaining hepatocyte phenotype and functioning, wherein the at least one topography is defined by:
 an average distance between adjacent protrusions between 3-25 μm;   the top surface area of the at least one protrusion element between 20 μm 2  and 250 μm 2 ; and   the plurality of protrusions covering 8% to 35% of the surface part.   
     
     
         13 . The object of  claim 1 , wherein:
 a height of each protrusion element is defined as a length of a longest straight-line fitting within a circumference of the top surface area parallel to the surface; and   a width of each protrusion element is defined as the length of the longest straight-line fitting within a circumference of the top surface area parallel to the surface perpendicular to the length, and is 0.01-100 μm.   
     
     
         14 . The object of  claim 13 , wherein an average distance between two circumferences of adjacent protrusion elements of the same protrusion is 0.5-50 μm. 
     
     
         15 . The object of  claim 1 , wherein at least a portion of each protrusion of the plurality of protrusions extends substantially normal to the surface where the circumferential side face intersects with the surface. 
     
     
         16 . The object of  claim 15 , wherein the at least the portion of each protrusion of the plurality of protrusions extends substantially normal to the surface at an angle in a range of about 88° to about 92°. 
     
     
         17 . A method for modulating at least one of morphology, proliferation, biochemical functioning, differentiation, attachment, migration, signaling or cell death of a cell population by physical stimulation, the method comprising:
 contacting cells of the cell population in a culture medium with a surface part of an object, the object having a plurality of individually spaced protrusions protruding from a surface of the surface part and defining a plurality of valleys between adjacent protrusions of the plurality of individually spaced protrusions, such that the adjacent protrusions do not touch, wherein the plurality of individually spaced protrusions are arranged in a regular pattern, defined by a grid of intersecting gridlines laid over the surface part, wherein the gridlines define a pattern of unit cells, such that each unit cell comprises a maximum of one protrusion, wherein each protrusion of the plurality of individually spaced protrusions comprises at least one protrusion element, wherein the at least one protrusion element comprises a surface portion which is elevated above the surface and which has a top surface area and a circumferential side face connecting the top surface area with the surface,   wherein the top surface area of the at least one protrusion element of each protrusion is a complex shape comprising a combination of basic shapes, interconnected by one or more overlapping portions, the basic shapes comprising one or more of a circular, oval, triangular, square, rectangular, trapezoidal, pentagonal, hexagonal, heptagonal or octagonal shape; and   allowing the one or more cells to respond to the surface part of the object.   
     
     
         18 . The method of  claim 17 , wherein the at least one protrusion element of each protrusion has a maximum height of between 0.5 and 50 μm above the surface,
 wherein an average distance between the adjacent protrusions is between 0.5 μm and 50 μm, 
 wherein the top surface area of the at least one protrusion element of each protrusion is between 1 and 6000 μm 2 , and 
 wherein the plurality of individually spaced protrusions cover between 3% and 90% of the surface. 
 
     
     
         19 . An object for altering cell behavior, the object comprising:
 a surface part having at least one topography for modulating one or more of morphology, proliferation, biochemical functioning, differentiation, attachment, migration, signaling, and cell death of a cell population by physical stimulation,   wherein the at least one topography comprises a surface and a plurality of protrusions protruding from the surface, wherein the plurality of protrusions are individually spaced and arranged in a regular pattern,   wherein the plurality of protrusions define a plurality of valleys between adjacent protrusions of the plurality of protrusions,   wherein each protrusion of the plurality of protrusions comprises at least one protrusion element, wherein the at least one protrusion element comprises a surface portion elevated above the surface and has a top surface area and a side face connecting the top surface area with the surface,   wherein the at least one protrusion element of each protrusion has a maximum height of between 0.5 μm and 50 μm above the surface,   wherein an average distance between the adjacent protrusions is between 0.5 μm and 50 μm, and   wherein the top surface area of the at least one protrusion element of each protrusion has a complex shape comprising a combination of basic shapes, interconnected by one or more bridging portions, the basic shapes comprising one or more of a circular, oval, triangular, square, rectangular, trapezoidal, pentagonal, hexagonal, heptagonal or octagonal shape.   
     
     
         20 . The object of  claim 19 , wherein:
 a height of each protrusion element is defined as a length of a longest straight-line fitting within a circumference of the top surface area parallel to the surface; and   a width of each protrusion element is defined as the length of the longest straight-line fitting within a circumference of the top surface area parallel to the surface perpendicular to the length.