GB2397233A

GB2397233A - Biomedical device with bioerodable coating

Info

Publication number: GB2397233A
Application number: GB0301238A
Authority: GB
Inventors: Julie Gold; Sarunas Petronis; Ann Wennerberg
Original assignee: Individual
Current assignee: Individual
Priority date: 2003-01-20
Filing date: 2003-01-20
Publication date: 2004-07-21
Also published as: GB0301238D0

Abstract

A biomedical device 2, such as an implant or tissue engineering scaffold, having a surface with a given topography, said surface is coated with a coating 1 comprising one or more layers 1a, 1b, 1c that is adapted to change with time. The outermost surface 1a of said coating has a different topography 3 than the underlying biomedical device. The coating 1 may comprise a bioerodable material that is adapted to degrade, melt and/or resorb upon contract with a biological environment.

Description

Biomedical device Technicalf eld The present invention refers to a

biomedical device having a surface with a given topography, said surface is coated with a coating, comprising one or more layers, that is adapted to change with time. It further refers to a precursor to a bioerodable coating intended to be applied to a biomedical device. It also refers to a method of preparing a biomedical device having a given surface topography and to a method of applying a biomedical device having a defined surface topography into a biological environment

Background of the invention

Most biomedical devices, which are both (1) devices used for clinical applications, e.g. medical implants, sensors, instruments, etc., and (2) devices used to handle or modify biological systems, e.g. cell culture substrates, bioreactors, tissue engineering scaffolds, IS etc., have parts made of biomaterials. Biomaterials are nonviable materials used in a device placed in direct contact with biological tissues, organisms or systems (Ratner, et al., Biomaterials science: An Introduction to Materials in Medicine, (1996)), and the main requirement for them is to perform with an appropriate biological response in a specific application, i.e. to be biocompatible (Williams, Definitions in Biomaterials; Progress in Biomedical Engineering 4 (1987)).

The biocompatibility of biomaterials can be determined by several factors depending on the type and status of the biological system as well as on the properties and intended function of the interacting material. The bulk properties of biomaterials are most important for the functionality of the specific device, e.g. the device must withstand specific load, mechanical wear, aggressive chemical environment, be transparent or electrically conductive, etc. However, as only the material surface is in direct contact with the biological environment, the biological response first of all depends on the material surface properties involved in reactions occurring at the material bioenvironment interface (Kasemo, et al., Implant Surfaces and Interface Processes; Adv. Dent. Res. 13 (1999) 8-20). Therefore tailoring of biomaterial surface properties for optimal biological response is one of the most important development directions in

the biomaterials field.

It is believed that the most important surface properties for materialbiosystem interactions are the chemical/physical properties (chemical composition, physical state, surface energy, Nettability, hardness, viscoelasticity and surface reactivity) and the topography (e.g. texture, roughness) of the surface (Kasemo, et al., Implant Surfaces and interface Processes, Adv. Dent. Res. 13 (1999) 8-20). These two classes of properties can be, and often are, correlated to each other, e.g. change in surface topography will affect surface mechanical properties. In this invention we are mainly focussed on the improving biocomatibility/performance of biomedical device caused by topographic factors, however the described methods and principles will also affect biochemical and mechanical surface properties which can be tailored to have an additional positive effect on the biocomatibility/performance of the device.

One of the surface topographic properties important for biocompatibility of medical implants is roughness. A rough surface, especially a microrough surface is favourable for different kinds of implants, such as orthopaedic and dental implants, intended to be anchored in bone tissue. Such surfaces provide better interlocking with surrounding tissue, promote larger direct bone contact and ostoeintegration in a long term.

Through for example Wen et al., Microrough Surface of Metallic Biomaterials: a literature review; Bio-Medical Materials and Engineering 6 (1996) 173-189 it is known that the roughness on the macroscopical level (>10,um) will influence the mechanical properties of the interface, the way stresses are distributed and transmitted, the mechanical interlocking of the interface and the biocompatibility of biomaterials.

On a smaller scale surface roughness in the range from 10 rim to 10,um may influence the interface biology, since it is of the same order of size as cells and large bio- molecules. Topography variations of the order of 10 rim and less may also become important, because nanoroughness on this scale length consists of material defects such as grain boundaries, steps, vacancies etc. These are all known to be active sites for adsorption and thus may influence the way biomolecules can bond to the implant surface. It is further known that surface roughness on a micron scale allows cellular adhesion that alters the overall tissue response to the biomaterials.

US-A-5,456,723 discloses that the bond between bone and an implant may be improved by providing the contact surface of the implant with a microroughness of 2,um or less.

Subjecting the contact surface to pickling in a reducing acid provides this microroughness.

US-A-5,588,838 discloses a dental implant with a circumferentially oriented micro roughness, preferably in the form of threads or beads, having a height between 0.02 and 0.20 mm.

US-A-6,069,295 teaches that an implant article is given a surface roughness with an average peak distance (Ra value) between 10 and 1000 rim by a mechanical or chemical surface treatment. In order to provide an effective bone formation, the roughened surface is subsequently subjected to precipitation of calcium phosphate from a solution containing calcium and phosphate ions.

Porous rough surfaces can have benefit to be used as drug carriers if loaded with bioactive substances. US-A-5,876,446 discloses a medical device, particularly a prosthesis having a porous tissue-mating surface. The pores or interstitial spaces of the porous surface are impregnated with a biodegradable polymer, said polymer containing a pharmacologically active substance, which is released over a certain period of time.

Roughness is usually provided as the random protrusions and/or cavities on the surface or porosity. But it can also be well-defined textures or a topographic patterns, e.g. grooves, ridges, pillars, pits, etc., of regular size and distribution. It has been shown by Brunette, Effects of surface topography of implant materials on cell behaviour in vitro and in viva; Nanofabrication and Biosystems (1996) 335-355, Curtis, et. al., Topographical control of cells; Biomaterials 18 (1997) 1573-1583 and others that textures on the surface may guide and orient several types of cells, affect their shape, proliferation, differentiation, motility, etc., both in vitro and in viva. For example, it has been shown that textured surfaces stop epithelial downgrowth and promote connective tissue ingrowth on the dental implant.

As stated above, microrough surfaces are favourable for providing a better interlocking with surrounding tissue, promoting larger direct bone contact and ostoeintegration in a the long term. However, during implant insertion/installation into bone, blood vessels and soft tissue, a microrough surface will damage the surrounding cells and tissues much more than a smooth surfaces. The loose parts of dead tissues and cells (debris) may then fill in cavities of the rough surface, which can cause inflammation or slow down short-term healing of the implant, which can be crucial for long-term biocompatability of the implant. Moreover, protrusions of the rough surface or the parts of the rough coating, may break off during implant insertion/installation into hard tissue due to high mechanical friction, and contaminate surrounding tissues as well as expose underlying implant surface in an uncontrolled way.

It would therefore be desired to have a different topography, specifically a less rough surface, during the implant insertion/installation, than during the healing/integration process of the implant with the surrounding body tissue that occurs when the implant is inserted in its final position. This demonstrates the general concept of the invention that biocompatibility/performance of biomedical device may be improved if surface properties (particularly topography) are made to change in time to optimally meet the surrounding biological system at defined points in time.

Besides smooth versus rough surfaces during implant installation and incorporation processes, respectively, in the above given example. It also may be desirable to have several (more than two) specifically engineered topographies at several (more than two) defined points in time.

For biomedical devices other than implants, it could also be desirable to have different surface topographies at different time periods. One example of such a biomedical device is a tissue engineering scaffold*, which is used in vitro or in viva to generate tissues or organs from a group of cells growing on some form of porous, three- dimensional shaped substrate ("scaffold"). Other similar examples are substrates for cell cultures, bioreactors, extra-corporeal life supporting equipment and bioelectronic interfaces. As stated above, in all these cases patterned surface topography can be used to locate specific cells types to specific positions on a substrate/scaffold and influence their function. For example it may be beneficial to use one kind of topography to induce higher motility of specific cell types so that those cells can spread over the substrate and follow guiding topographic cues into specific locations. Later, another type of topography would be desirable for switching-on proliferation cycle in the cells, and finally, determine cell differentiation.

Object and most important features of the invention The object of the present invention is to provide a biomedical device which is adapted to have different surface topographies at different time periods. This has according to the invention been provided by the fact that the biomedical device is coated with a coating comprising one or more layers that is adapted to change with time and that the outermost surface of said coating has a different topography than the underlying biomedical device.

The coating preferably comprises a bioerodable material that is adapted to degrade, melt and/or resorb upon contact with a biological environment.

Examples of biomedical devices are implants and tissue engineering scaffolds. Other similar examples are substrates for cell cultures, bioreactors, extra-corporeal life supporting equipment and bioelectronic interfaces.

The outermost surface of the coating and the surface of the underlying biomedical device have topographies with given values of the following topographic parameters: (a) roughness amplitude, (b) slope and curvature of individual irregularities, (c) developed surface area, and (d) peak/valley density over a surface area of at least l00,um x 100 Em, and that one or more of said parameters has a significantly lower value in the coating surface than in the underlying biomedical device surface.

In this respect a significantly lower value means that one or more of said topographic parameters is reduced at least 10%, preferably at least 25% and more preferably at least 50% in the coating surface as compared to the underlying biomedical device surface.

At least two, preferably at least three and more preferably all four of said topographic parameters have a significantly lower value in the coating surface as compared to the underlying biomedical device surface.

The coating or at least one outermost layer thereof is adapted to resist significant bioerosion upon contact with a biological environment for a time period sufficient for accomplishing a completed installation of the biomedical device into its final working location. Said time period is in the range from several seconds to several days. Each layer of the coating may have specific bioerosion rates and times.

The bioerodable material in the coating is chosen from the following group of materials: a ceramic material, a polymeric material of synthetic and/or biological origin and/or a material that melts at a temperature lower than body temperature, said material upon contact with a biological environment will melt, degrade and/or resorb into biocompatible products.

In a specific embodiment the coating carries a bioactive substance, which may be chosen from the following group of substances: anti-infective substances, anti al lergenic s, anti -infl ammatories, inflammatories, hormones and humoral agents, antipyeretics, anti-coagulants, healing enhancing substances, growth factors, nutritional agents and/or osteoinductive substances.

The coating may according to an embodiment comprise more than one layer, each having different topographies which are intended to be exposed to a surrounding biological environment at different time points. Also, each of such layers of the coating may according to another aspect of the invention have different mechanical properties, such as viscoelastic properties, hardness, stiffness, shear modulus and/or friction, than the underlying biomedical device.

The layers of the coating may also or alternatively have different electromagnetical properties and/or optical properties than the underlying biomedical device.

The invention further refers to a precursor of a bioerodable material, said precursor is intended to be applied to a biomedical device comprising a material having a defined surface topography and accumulate into pores and valleys of said surface thus making the surface less rough and that said precursor is adapted to harden to a solid coating of said bioerodable -material on said biomedical device, said coating is stable in air but degrades, melts and/or resorbs upon contact with a biological environment.

The invention also refers to a method of preparing a biomedical device having a given topography, comprising preparing a precursor phase of a bioerodable -material, depositing said precursor phase on said biomedical device so that is accumulates into cavities and pores of the surface thus changing the topography thereof, bringing the precursor phase to harden thus forming a solid coating of said bioerodable polymeric material on said biomedical device, said coating being stable in air but is degradable, meltable and/or resorbable upon contact with a biological environment.

According to a further aspect the invention refers to a method of applying a biomedical device having a defined surface topography into a biological environment, wherein a coating comprising one or more layers is applied on said biomedical device, the outermost surface of said coating has a different topography than the underlying biomedical device, said coating being adapted to change with time in contact with a biological environment; applying the coated biomedical device into a biological environment, at which said coating will change with time. The coating comprises preferably a bioerodable material that is adapted to degrade, melt and/or resorb upon contact with a biological environment.

Description of drawings

The invention will below be closer described with reference to the accompanying drawing showing an embodiment of the invention.

Figure 1 shows schematically a section through a biomedical device provided with a smooth coating according to the invention.

Figure 2 shows schematically a section through a biomedical device provided with a multi-layered coating according to the invention.

Description of the invention

Implant surface topography is one of the major factors determining surrounding tissue response to the inserted implant. In some cases it would be favourable to have different implant topography at different time points of treatment in order to optimize implant healing. A few examples can be that it would be desirable to have an initially smooth surface of bone implants or cardiovascular stents in order to facilitate their insertion into bone or blood vessels and which surface then becomes rough to improve the implant fixation and stability.

According to the present invention such dynamics of the implant topography is achieved by depositing a coating l of a bioerodable material on an implant 2 having a surface roughness 3. The coating 1 will accumulate into pores and valleys of the rough surface thus making the surface less rough. The term bioerodable material is defined as a material that is converted in a biological environment into biocompatible products.

The conversion process could involve both physical processes such as dissolution and melting and chemical and biological processes, such as backbone cleavage of a polymer either hydrolytic, enzymatic or microbiotic cleavage. The biological environment could be any environment in which a biologic activity takes place. In the case of an implant the biological environment is a living organism. In the case of a tissue engineering scaffold or other substrates for growing cell cultures, the biological environment is either a bioreactor or tissue culture dish with defined tissue/cell culture media or body fluid or a living organism, depending on where the cell growth and/or tissue formation is intended to take place.

The coating of bioerodable material should be stable in air, but upon contact with a biological environment, such as body tissues and/or body fluids it should gradually degrade, melt and/or resorb into biocompatible products, which can be digested by the body. This process may proceed rapidly in less than an hour, such as several seconds or minutes, or take several hours or even days. As the bioerodable coating is degraded/resorbed in the body the rough surface of the implant will be gradually exposed to the surrounding body tissue.

The coating 1 may consist of only one layer and have a substantially smooth surface, as is shown in Fig. 1. The coating may alternatively consist of two or more layers la, lb and to as shown in Fig. 2, which shows a coating comprising three layers. These layers may have different topographies, such that the outermost layer la have a substantially smooth, and the underlying coating layers have surfaces in the form of well-defined textures or topographic patterns, e.g. grooves, ridges, pillars, pits, etc., of regular size and distribution. These additional coating layers lb and 1c, which will be exposed to the implant-tissue interface at a specific time, can have a different functional topography adapted for optimized healing and performance of the implant in the body.

The roughness of a surface can be quantified in different ways, such as by mechanical electronic profilometers, optical profilometers and/or scanning probe microscopy (SPM). Several standard parameters are commonly used for quantifying the degree of roughness of a surface. These parameters are (l) roughness amplitude (e.g. Ra, Rvq, Rat, Rz Sa, Svq, So, Sz), (2) slope and curvature of individual irregularities (e.g. Rvq, Svq), (3) developed and projected surface area ratio (e.g. Rd.s, Sd5) and (4) peak/valley density (e.g. Spd, So). These parameters should be measured -over a surface area of at least lOO,um x lOO,um. ''Rx'' notation is usually used for 2D profile measurements by 1-line scan on the surface; ''Sx'' is used for noting 3D measurements by area scan on the surface. Both types of measurements are acceptable for surfaces with random topography, but in the cases when the surface is anisotropic, e.g. contains furrows, grooves, pits, regular patterns and textures, only 3D measurement can give realistic description of the surface topography. Therefore only ''Sx'' rotation is used in the text below.

Sa - arithmetic-mean deviation of surface topography, also called average roughness. It is defined as the mean deviation of the real surface from the mean-plane over the sampling area.

Svq - the root-mean-square (rms) deviation of surface topography. Svq has statistical significance as the standard deviation of the profile height distribution. It is correlated with Sa, but is more sensitive to the very large and small height values of the profile.

Sit - the maximum peak-to-valley height of theprofile surface in the assessment area.

Sz - topography height is the average sum of the five largest surface peak heights and the five largest surface valley depths within a sampling area.

Svq - the root-mean-square slope of the surface irregularities throughout the assessment area, measured in degrees.

Sds - the ratio of the developed surface area and the projected sampling area Sp, - peak density, a number of peaks per area unit within a sampling area Svd - valley density, a number of valleys per area unit within a sampling area The term rough surface used herein refers to a surface having a Sa-value >10 nm (0.01 um). A smoothening coating can thus be applied to any surface having a Sa>10 nm.

One or more of the above parameters should have a significantly lower value in the outermost coating surface than in the underlying biomedical device surface. In this respect a significantly lower value means that one or more of said topographic parameters is reduced at least 10%, preferably at least 25% and more preferably at least 50% in the coating surface as compared to the underlying biomedical device surface.

At least two, preferably at least three and more preferably all four of said topographic parameters should have a significantly lower value in the coating surface as compared to the underlying biomedical device surface.

The layers of the coating may according to another aspect of the invention have different than the underlying biomedical device mechanical properties, which affect biocompatibility of the biomedical device. The most important biologically relevant mechanical properties would be hardness, stiffness, viscoelastic properties (elastic modulus, dynamic modulus, storage modulus, loss modulus, viscosity coefficient), shear modulus and/or friction. These mechanical properties are measured by nanoindentation, microrheometry, quartz crystal resonator (QCR) and/or atomic force microscopy (AFM) in lateral force-, force modulation- and phase imaging modes.

The coating may also or alternatively have different electromagnetical properties and/or optical properties than the underlying biomedical device. This could be beneficial for certain fields of applications, such as for stimulators for bone growth and remodelling, nerve guides, biosensors, intaocular lenses, image enhancement during insertion or post implantation follow-up (for example by ultrasound, X-ray, MRI, NMR, etc), etc. The biomedical device onto which the coating is applied is not restricted to implants intended to be implanted in a living organism, but may also be a tissue engineering scaffold, substrates for cell cultures, bioreactors, extra-corporeal life supporting equipment and bioelectronic interfaces. In these cases patterned surface topography can be used to locate specific cell types to specific positions on a substrate/scaffold and influence their function. For example it may be beneficial to use one kind of topography to induce higher motility of specific cell types so that those cells can spread over the substrate and follow guiding topographic cues into specific locations. Later, another type of topography would be desirable for switching-on proliferation cycle in the cells, and finally, determine cell differentiation. A tissue engineering scaffold can be used in vitro or in vivo to generate tissues or organs from a group of cells growing on some form of porous, three-dimensional shaped substrate ("scaffold"). Patterned surface topography can be used to guide and/or orient cells to specific locations on a surface. It would be beneficial to help guide specific cell types to specific locations on a tissue engineering scaffold to help in the early phase of tissue organization. However, as cells begin to propagate, they interact and begin to define their own organization and then the desired guidance cues from the substrate will change or might be eliminated entirely. It would be beneficial if the biodegrading coating could release, in a controlledway, bioactive chemical factors, which would further influence the cell behaviour separately or in synergy with topographic cues.

Other biomedical devices onto which coatings could be applied are implantable biosensors. Smooth coatings provide protection from damage of surrounding tissues during insertion of the sensor. The coating could contain image contrast agents to aid in the placement of the sensor by non-invasive imaging techniques, such as computer aided tomography.

The coating material should have the following properties: 1. It should have a homogeneous or suspension-like fluid precursor phase, or alternatively be soluble or meltable.

2. The liquid precursor phase should wet the device surfaces and have an adjustable viscosity so that when deposited on rough surfaces it will accumulate into micro- cavities/pores and make the surface smoother.

3. After deposition, which may take place through dipping of the device in the precursor phase, the coating should harden to be mechanically strong and stable in air. The hardening can take place for example by curing, drying, solvent removal or freezing.

4. When brought in contact with a biological environment, such as body tissue or body fluid, the coating material should melt or resorb/degrade in a timely manner into biocompatible products, which can be digested by the body.

Examples of suitable coating materials are polymers derived from lactic and glycolic acid, polydioxanone, polyanhydrides derived from sebacic acid and bis(p-carboxy phenoxy)propane or biodegradable/bioresorbable polymers of biological origin, such as polysaccharides, e g cellulose, starch.

Other examples are ceramic materials, such as the calcium phosphate and bioactive glass families of minerals, -or materials that melts at a temperature lower than body temperature, for example ice.

The coating material, or at least one layer thereof, may according to a further aspect of the invention serve as a carrier/matrix for releasing bioactive substances 4, such as anti- infective substances, anti-allergenics, anti-inflammatories, inflammatories, estrogens, progestrational agents, humoral agents, antipyeretics, anti-coagulants, healing enhancing substances, body tissue ingrowth substances, nutritional agents and/or osteoinductive substances. antibiotics, and/or substances inducing healing/bone ingrowth.

The coating material can be provided to the end user in different ways. Firstly it can be delivered as a part of the biomedical device and thus be applied to the device in the production plant. Secondly it can be delivered as a separate product for application to an existing commercial biomedical device in clinics or laboratories. In the latter case it is delivered as a precursor, which may be deposited directly on the biomedical device surface or be melted or dissolved to a fluid phase before deposition on the implant surface.

S An implant having a rough surface provided with a smooth biodegradable/bioresorbable coating according to the invention may have the following important advantages: 1. A reduced initial inflammatory reaction, which may be caused when inserting an implant having a rough surface.

2. An induced faster tissue regeneration around the implant, due to a reduced destruction of contacting tissue.

3. A better stability of original implant surface during the storage, transportation and insertion periods.

4. An improved implant integration and thus lower long- term failure rate.

S. A faster healing and patient treatment. À 14

Claims

Claims 1. A biomedical device having a surface with a given topography,

characterized in that said surface is coated with a coating (1) comprising one or more layers, that is adapted to change with time and that the outermost surface of said coating has a different topography than the underlying biomedical device (2)
2. A biomedical device as claimed in claim 1, characterized in that said coating (1) comprises a bioerodable material that is adapted to degrade, melt and/or resorb upon contact with a biological environment.
3. A biomedical device as claimed in claim 1 or 2, characterized in that said biomedical device (2) is a medical implant.
4. A biomedical device as claimed in claims 1 or 2, characterized in that said biomedical device (2) is a device for growing cells or tissues.
5. A biomedical device as claimed in any of the preceding claims, characterized in that the outermost surface of the coating (1) and the surface of the underlying biomedical device (2) have topographies with given values of the following topographic parameters: (a) roughness amplitude, (b) slope and curvature of individual irregularities, (c) developed and projected surface area ratio and (d) peak/valley density over a surface area of at least lOO,um x 100,um, and that one or more of said parameters has a significantly lower value in the coating surface than in the underlying biomedical device surface.
6. A biomedical device as claimed in claim 5, characterised in that one or more of said topographic parameters is reduced at least 10%, preferably at least 25% and more preferably at least 50% in the coating surface as compared to the underlying biomedical device surface.
7. A biomedical device as claimed in claims 5 or 6, i characterised in at least two, preferably at least three and more preferably all four of said topographic parameters have a significantly lower value in the coating surface as compared to the underlying biomedical device surface.
8. A biomedical device as claimed in any of the preceding claims, characterized in that the coating (1) or at least one outermost layer thereof is adapted to resist significant bioerosion upon contact with a biological environment for a time period sufficient for accomplishing a completed installation period of a biomedical device, or desired cell attachment period for a tissue engineering scaffold..
9. A biomedical device as claimed in claim 8, characterized in that said time period is in the range from several seconds to several days.
10. A biomedical device as claimed in any of the preceding claims, characterized in that said bioerodable material in the coating is chosen from the following group of materials: a ceramic material, a polymeric material of synthetic and/or biological origin and/or a material that melts at a temperature lower than body temperature, said material upon contact with a biological environment will melt, degrade and/or resorb into biocompatible products.
11. A biomedical device as claimed in any of the preceding claims, characterized in that said coating carries a bioactive substance (4). 1:
12. A biomedical device as claimed in claim 11, characterised in that said bioactive substance is chosen from the following group of substances: anti infective substances, anti-allergenics, anti- inflammatories, inflammatories, hormones and humoral agents, antipyeretics, anti-coagulants, healing enhancing substances, gorwth factors, nutritional agents and/or osteoinductive substances.
13. A biomedical device as claimed in any of the preceding claims, characterised in that the coating (1) comprises at least two layers (la, lb) having different topographies which are intended to be exposed to a surrounding biological environment at different time points.
14. A biomedical device as claimed in any of the preceding claims, characterized in that the coating (1) comprises at least one layer having different mechanical properties, such as hardness, stiffness, viscoelastic properties, shear modulus and/or friction, than the underlying biomedical device.
15. A biomedical device as claimed in any of the preceding claims, characterized in that the coating (1) has different electromagnetical properties than the underlying biomedical device.
16. A biomedical device as claimed in any of the preceding claims, characterized in that the coating (1) has different optical properties than the underlying biomedical device.
17. A precursor to a bioerodable material, characterized in that said precursor is intended to be applied to a biomedical device comprising a material having a defined surface topography and accumulate into pores and valleys of said surface thus making the surface less rough and that said precursor is adapted to harden to a solid coating (1) of said bioerodable material on said biomedical device (2), said coating being stable in air but is degradable, meltable and/or resorbable upon contact with a biological environment.
18. A method of preparing a biomedical device having a given topography, characterised in preparing a precursor phase of a bioerodable material, depositing said precursor phase on said biomedical device so that is accumulates into cavities and pores of the surface thus changing the topography thereof, bringing the precursor phase to harden thus forming a solid coating (1) of said bioerodable polymeric material on said biomedical device (2), said coating being stable in air but is degradable, meltable and/or resorbable upon contact with a biological environment.
19. A method of applying a biomedical device having a defined surface topography into a biological environment, characterized in applying a coating (1) comprising one or more layers on said biomedical device (2), the outermost surface of said coating has a different topography than the underlying biomedical device, said coating being adapted to change with time in contact with a biological environment; applying the coated biomedical device into a biological environment, at which said coating will change with time.
20. A method as claimed in claim 19, characterized in that said coating (1) comprises a bioerodable material that is adapted to degrade, melt and/or resorb upon contact with a biological environment.