Thermo-mechanically controlled implants and methods of use

Abstract

An implant comprises a structure that may be implanted into tissue and that has a first material property at normal body temperature. The first material property is variable at elevated temperatures above normal body temperature. The implant also has a plurality of particles dispersed in the structure that are adapted to convert incident radiation into heat energy when irradiated with electromagnetic radiation. The particles are in thermal contact with the structure such that exposure of the particles to incident radiation raises the temperature of the structure thereby changing the first material property relative to the first material property at normal body temperature.

1 . An implant for use in tissue, the implant comprising:
 a structure adapted for implantation into the tissue, the structure having a first material property at normal body temperature, the material property being variable at an elevated temperature above normal body temperature; and   a plurality of particles dispersed in the structure, the particles adapted to convert incident radiation into heat energy when irradiated with electromagnetic radiation, and wherein the particles are in thermal contact with the structure such that exposure of the particles to the incident radiation raises the temperature of the structure thereby changing the first material property.   
     
     
         2 . An implant according to  claim 1 , wherein the material property is the ability of the structure to be plastically expanded and wherein the structure is not plastically expandable at normal body temperatures but is plastically deformable at an elevated temperature above normal body temperature. 
     
     
         3 . An implant according to  claim 1 , wherein the structure is biodegradable and the material property is the biodegradation rate of the structure. 
     
     
         4 . An implant according to  claim 1 , wherein the material property is the viscosity of the structure, the structure having a lower viscosity at an elevated temperature above normal body temperature. 
     
     
         5 . An implant according to  claim 1 , wherein the particles comprise nanoparticles. 
     
     
         6 . An implant according to  claim 1 , wherein the particles comprise a non-conducting core layer having a first thickness and a conducting outer shell layer adjacent to the core layer having a second thickness. 
     
     
         7 . An implant according to  claim 6 , wherein the ratio of the first thickness to the second thickness defines a maximum wavelength of electromagnetic radiation converted by the particles into heat. 
     
     
         8 . An implant according to  claim 6 , wherein the outer layer comprises gold. 
     
     
         9 . An implant according to  claim 6 , wherein the core layer comprises silicon dioxide. 
     
     
         10 . An implant according to  claim 1 , wherein the particles comprise nanoshells. 
     
     
         11 . An implant according to  claim 1 , wherein the particles are substantially spherical. 
     
     
         12 . An implant according to  claim 1 , wherein the structure is biodegradable. 
     
     
         13 . An implant according to  claim 1 , wherein the structure comprises a polymer. 
     
     
         14 . An implant according to  claim 1 , wherein the structure comprises a natural polymer. 
     
     
         15 . An implant according to  claim 1 , wherein the structure comprises a synthetic polymer. 
     
     
         16 . An implant according to  claim 1 , wherein the structure comprises a copolymer. 
     
     
         17 . An implant according to  claim 1 , wherein the structure comprises a material selected from the group consisting of polyhydroxyalkanoates, polyalphahydroxy acids, polysaccharides, proteins, hydrogels, lignin, shellac, natural rubber, polyanhydrides, polyamide esters, polyvinyl esters, polyvinyl alcohols, polyalkylene esters, polyethylene oxide, polyvinylpyrrolidone, polyethylene maleic anhydride, poly(glycerol-sibacate) and polyphosphazenes. 
     
     
         18 . An implant according to  claim 1 , wherein the structure comprises poly-L-lactide. 
     
     
         19 . An implant according to  claim 1 , wherein the structure comprises poly-DL-lactide. 
     
     
         20 . An implant according to  claim 1 , wherein the structure comprises poly-ε-caprolactone. 
     
     
         21 . An implant according to  claim 1 , wherein the structure comprises a plasticizer adapted to soften the structure. 
     
     
         22 . An implant according to  claim 1 , wherein the structure comprises a biological fluid in the solid state. 
     
     
         23 . An implant according to  claim 22 , wherein the biological fluid comprises blood plasma. 
     
     
         24 . An implant according to  claim 1 , wherein the structure is a stent. 
     
     
         25 . An implant according to  claim 24 , wherein the stent is tubular and is radially expandable at the elevated temperature. 
     
     
         26 . An implant according to  claim 24 , wherein the stent comprises a tube having a sidewall, the sidewall defining a plurality of openings therein. 
     
     
         27 . An implant according to  claim 1 , wherein the structure is adapted to be implanted into a breast. 
     
     
         28 . An implant according to  claim 1 , wherein the structure is adapted to exclude an aneurysm. 
     
     
         29 . An implant according to  claim 1 , wherein the structure is an orthopedic implant. 
     
     
         30 . An implant according to  claim 1 , wherein the elevated temperature is in the range from about 38° C. to about 60° C. 
     
     
         31 . An apparatus according to  claim 1 , wherein the electromagnetic radiation is one of ultraviolet, visible, near infrared and infrared light. 
     
     
         32 . An implant according to  claim 1 , wherein the structure carries a therapeutic agent adapted to be released therefrom in a controlled manner. 
     
     
         33 . An implant according to  claim 32 , wherein the therapeutic agent inhibits restenosis. 
     
     
         34 . An implant according to  claim 32 , wherein the therapeutic agent comprises at least one of antibiotics, thrombolytics, anti-thrombotics, anti-inflammatories, cytotoxic agents, anti-proliferative agents, vasodilators, gene therapy agents, radioactive agents, immunosuppressants, chemotherapeutics, endothelial cell attractors, endothelial cell promoters, stem cells and combinations thereof. 
     
     
         35 . An expandable implant for use in tissue, the implant comprising:
 a structure adapted for implantation into the tissue, wherein the structure is not plastically deformable at normal body temperatures but is plastically deformable at an elevated temperature above normal body temperature; and   a plurality of particles dispersed in the structure, the particles adapted to convert incident radiation into heat energy when irradiated with electromagnetic radiation, and wherein the particles are in thermal contact with the structure such that exposure of the particles to the incident radiation raises the temperature of the structure allowing plastic deformation thereof.   
     
     
         36 . An implant according to  claim 35 , wherein the particles comprise nanoparticles. 
     
     
         37 . An implant according to  claim 35 , wherein the particles comprise a non-conducting core layer having a first thickness and a conducting outer shell layer adjacent to the core layer having a second thickness. 
     
     
         38 . An implant according to  claim 37 , wherein the ratio of the first thickness to the second thickness defines a maximum wavelength of electromagnetic radiation converted into heat by the particles. 
     
     
         39 . An implant according to  claim 37 , wherein the outer layer comprises gold. 
     
     
         40 . An implant according to  claim 37 , wherein the core layer comprises silicon dioxide. 
     
     
         41 . An implant according to  claim 35 , wherein the particles comprise nanoshells. 
     
     
         42 . An implant according to  claim 35 , wherein the particles are substantially spherical. 
     
     
         43 . An implant according to  claim 35 , wherein the structure is biodegradable. 
     
     
         44 . An implant according to  claim 35 , wherein the structure comprises a polymer. 
     
     
         45 . An implant according to  claim 35 , wherein the structure comprises a copolymer. 
     
     
         46 . An implant according to  claim 35 , wherein the structure comprises a natural polymer. 
     
     
         47 . An implant according to  claim 35 , wherein the structure comprises a synthetic polymer. 
     
     
         48 . An implant according to  claim 35 , wherein the structure comprises a material selected from the group consisting of polyhydroxyalkanoates, polyalphahydroxy acids, polysaccharides, proteins, hydrogels, lignin, shellac, natural rubber, polyanhydrides, polyamide esters, polyvinyl esters, polyvinyl alcohols, polyalkylene esters, polyethylene oxide, polyvinylpyrrolidone, polyethylene maleic anhydride and poly(glycerol-sibacate) and polyphosphazenes. 
     
     
         49 . An implant according to  claim 35 , wherein the structure comprises poly-L-lactide. 
     
     
         50 . An implant according to  claim 35 , wherein the structure comprises poly-DL-lactide. 
     
     
         51 . An implant according to  claim 35 , wherein the structure comprises poly-ε-caprolactone. 
     
     
         52 . An implant according to  claim 35 , wherein the structure comprises a plasticizer adapted to soften the structure. 
     
     
         53 . An implant according to  claim 35 , wherein the structure is a stent. 
     
     
         54 . An implant according to  claim 53 , wherein the stent is tubular and is radially expandable at the elevated temperature. 
     
     
         55 . An implant according to  claim 53 , wherein the stent comprises a tube having a sidewall, the sidewall defining a plurality of openings therein. 
     
     
         56 . An implant according to  claim 35 , wherein the structure is adapted to be implanted into a breast. 
     
     
         57 . An implant according to  claim 35 , wherein the structure is adapted to exclude an aneurysm. 
     
     
         58 . An implant according to  claim 35 , wherein the structure is an orthopedic implant. 
     
     
         59 . An implant according to  claim 35 , wherein the elevated temperature is in the range from about 38° C. to about 60° C. 
     
     
         60 . An apparatus according to  claim 35 , wherein the electromagnetic radiation is one of ultraviolet, visible, near infrared and infrared light. 
     
     
         61 . An implant according to  claim 35 , wherein the structure carries a therapeutic agent adapted to be released therefrom in a controlled manner. 
     
     
         62 . An implant according to  claim 61 , wherein the therapeutic agent inhibits restenosis. 
     
     
         63 . An implant according to  claim 61 , wherein the therapeutic agent comprises at least one of antibiotics, thrombolytics, anti-thrombotics, anti-inflammatories, cytotoxic agents, anti-proliferative agents, vasodilators, gene therapy agents, radioactive agents, immunosuppressants, chemotherapeutics, endothelial cell attractors, endothelial cell promoters, stem cells and combinations thereof. 
     
     
         64 . An expandable, biodegradable implant for use in tissue, the implant comprising:
 a biodegradable structure adapted for implantation into the tissue, wherein the structure degrades at a first rate when implanted in the tissue at normal body temperature; and   a plurality of particles dispersed in the structure, the particles adapted to convert incident radiation into heat energy when irradiated with electromagnetic radiation, and wherein the particles are in thermal contact with the structure such that exposure of the particles to the incident radiation raises the temperature of the structure thereby increasing the degradation rate of the structure relative to the first rate.   
     
     
         65 . An implant according to  claim 64 , wherein the particles comprise nanoparticles. 
     
     
         66 . An implant according to  claim 64 , wherein the particles comprise a non-conducting core layer having a first thickness and a conducting outer shell layer adjacent to the core layer having a second thickness. 
     
     
         67 . An implant according to  claim 66 , wherein the ratio of the first thickness to the second thickness defines a maximum wavelength of electromagnetic radiation converted into heat by the particles. 
     
     
         68 . An implant according to  claim 66 , wherein the outer layer comprises gold. 
     
     
         69 . An implant according to  claim 66 , wherein the core layer comprises silicon dioxide. 
     
     
         70 . An implant according to  claim 64 , wherein the particles comprise nanoshells. 
     
     
         71 . An implant according to  claim 64 , wherein the particles are substantially spherical. 
     
     
         72 . An implant according to  claim 64 , wherein the structure comprises a polymer. 
     
     
         73 . An implant according to  claim 64 , wherein the structure comprises a copolymer. 
     
     
         74 . An implant according to  claim 64 , wherein the structure comprises a natural polymer. 
     
     
         75 . An implant according to  claim 64 , wherein the structure comprises a synthetic polymer. 
     
     
         76 . An implant according to  claim 64 , wherein the structure comprises a material selected from the group consisting of polyhydroxyalkanoates, polyalphahydroxy acids, polysaccharides, proteins, hydrogels, lignin, shellac, natural rubber, polyanhydrides, polyamide esters, polyvinyl esters, polyvinyl alcohols, polyalkylene esters, polyethylene oxide, polyvinylpyrrolidone, polyethylene maleic anhydride and poly(glycerol-sibacate) and polyphosphazenes. 
     
     
         77 . An implant according to  claim 64 , wherein the structure comprises poly-L-lactide. 
     
     
         78 . An implant according to  claim 64 , wherein the structure comprises poly-DL-lactide. 
     
     
         79 . An implant according to  claim 64 , wherein the structure comprises poly-ε-caprolactone. 
     
     
         80 . An implant according to  claim 64 , wherein the structure is a stent. 
     
     
         81 . An implant according to  claim 80 , wherein the stent is tubular and is radially expandable at the elevated temperature. 
     
     
         82 . An implant according to  claim 80 , wherein the stent comprises a tube having a sidewall, the sidewall defining a plurality of openings therein. 
     
     
         83 . An implant according to  claim 64 , wherein the structure is adapted to be implanted into a breast. 
     
     
         84 . An implant according to  claim 64 , wherein the structure is adapted to exclude an aneurysm. 
     
     
         85 . An implant according to  claim 64 , wherein the structure is an orthopedic implant. 
     
     
         86 . An implant according to  claim 64 , wherein the elevated temperature is in the range from about 38° C. to about 60° C. 
     
     
         87 . An apparatus according to  claim 64 , wherein the electromagnetic radiation is one of ultraviolet, visible, near infrared and infrared light. 
     
     
         88 . An apparatus according to  claim 64 , further comprising a carrier dispersed in the structure and carrying a reagent, wherein exposure of the particles to the incident radiation raises the temperature of the carrier thereby releasing the reagent therefrom, the reagent adapted to react with the structure so as to increase the degradation rate of the structure relative to the first rate. 
     
     
         89 . An apparatus according to  claim 88 , wherein the carrier comprises a microsphere. 
     
     
         90 . An apparatus according to  claim 88 , wherein the carrier comprises a hydrogel. 
     
     
         91 . An apparatus according to  claim 88 , wherein the carrier comprises a catalyst. 
     
     
         92 . An apparatus according to  claim 88 , wherein the reagent comprises an enzyme. 
     
     
         93 . An implant according to  claim 64 , wherein the implant carries a therapeutic agent adapted to be released therefrom in a controlled manner. 
     
     
         94 . An implant according to  claim 93 , wherein the therapeutic agent inhibits restensosis. 
     
     
         95 . An implant according to  claim 93 , wherein the therapeutic agent comprises at least one of antibiotics, thrombolytics, anti-thrombotics, anti-inflammatories, cytotoxic agents, anti-proliferative agents, vasodilators, gene therapy agents, radioactive agents, immunosuppressants, chemotherapeutics, endothelial cell attractors, endothelial promoters, stem cells and combinations thereof. 
     
     
         96 . A method of controlling a material property of an implant, the method comprising:
 providing an implant having a plurality of particles dispersed therein and wherein the implant has a first material property when implanted in tissue at normal body temperature, the material property being variable at an elevated temperature above normal body temperature; and   exposing the implant to electromagnetic radiation, the incident radiation being converted into heat energy thus raising the temperature of the implant above normal body temperature, thereby changing the material property relative to the first material property.   
     
     
         97 . The method of  claim 96 , wherein the material property is the ability of the structure to be plastically deformed and wherein the structure is not plastically deformable at normal body temperatures but is plastically deformable at an elevated temperature above normal body temperature. 
     
     
         98 . The method of  claim 96 , wherein the implant is biodegradable and the first material property is the biodegradation rate of the implant. 
     
     
         99 . The method of  claim 96 , wherein the material property is the viscosity of the structure, the structure having a lower viscosity at an elevated temperature above normal body temperature. 
     
     
         100 . The method of  claim 96 , further comprising discontinuing exposure of the implant to the electromagnetic radiation thereby allowing the implant to cool down so that it returns to body temperature, the implant being substantially undeformable plastically at body temperature. 
     
     
         101 . The method of  claim 96 , further comprising monitoring the temperature of the implant. 
     
     
         102 . The method of  claim 96 , wherein the implant temperature is raised to a temperature in the range from about 38° C. to about 60° C. 
     
     
         103 . The method of  claim 96 , wherein the implant is a stent. 
     
     
         104 . The method of  claim 96 , further comprising implanting the implant into a breast. 
     
     
         105 . The method of  claim 96 , further comprising excluding an aneurysm with the implant. 
     
     
         106 . The method of  claim 96 , wherein the implant is an orthopedic implant. 
     
     
         107 . The method of  claim 96 , wherein the particles are nanoparticles. 
     
     
         108 . The method of  claim 96 , wherein the particles are nanoshells. 
     
     
         109 . The method of  claim 108 , wherein the nanoshells comprise a non-conducting core layer and a conducting outer shell layer. 
     
     
         110 . The method of  claim 96 , wherein the electromagnetic radiation is one of ultraviolet, visible, near infrared and infrared light. 
     
     
         111 . The method of  claim 96 , wherein exposing the implant to electromagnetic radiation comprises exposing the implant to the electromagnetic radiation extracorporally. 
     
     
         112 . The method of  claim 96 , wherein exposing the implant to electromagnetic radiation comprises exposing the implant to the electromagnetic radiation from within the body. 
     
     
         113 . The method of  claim 96 , wherein exposing the implant to electromagnetic radiation comprises delivering electromagnetic radiation to the implant with a catheter. 
     
     
         114 . The method of  claim 96 , wherein exposing the implant to electromagnetic radiation comprises delivering the radiation for a fixed duration of time. 
     
     
         115 . The method of  claim 96 , wherein exposing the implant to electromagnetic radiation comprises delivering the radiation until a desired temperature is obtained in the implant. 
     
     
         116 . The method of  claim 96 , wherein exposing the implant to electromagnetic radiation comprises delivering the radiation over periodic intervals. 
     
     
         117 . The method of  claim 96 , wherein exposing the implant to electromagnetic radiation comprises delivering the radiation continuously during a defined period. 
     
     
         118 . The method of  claim 96 , wherein the implant is biodegradable. 
     
     
         119 . The method of  claim 96 , further comprising releasing a therapeutic agent from the implant in a controlled manner. 
     
     
         120 . The method of  claim 119 , wherein the therapeutic agent inhibits restenosis. 
     
     
         121 . The method of  claim 119 , wherein the therapeutic agent comprises at least one of antibiotics, thrombolytics, anti-thrombotics, anti-inflammatories, cytotoxic agents, anti-proliferative agents, vasodilators, gene therapy agents, radioactive agents, immunosuppressants, chemotherapeutics, endothelial cell attractors, endothelial cell promoters, stem cells and combinations thereof. 
     
     
         122 . A method of delivering an expandable implant to a treatment site in a body, the method comprising:
 providing an implant having a plurality of particles dispersed therein;   positioning the implant at the treatment site;   exposing the implant to electromagnetic radiation, the particles converting the incident radiation into heat energy thereby raising the temperature of the implant above the implant glass transition temperature; and   plastically deforming the implant so as to change the shape of the implant.   
     
     
         123 . The method of  claim 122 , further comprising discontinuing exposure of the implant to the electromagnetic radiation thereby allowing the implant to cool down so that it returns to body temperature, the implant being substantially undeformable plastically at body temperature. 
     
     
         124 . The method of  claim 122 , wherein expanding the implant comprises expanding a balloon. 
     
     
         125 . The method of  claim 122 , further comprising monitoring the temperature of the implant. 
     
     
         126 . The method of  claim 122 , wherein positioning the implant comprises advancing a catheter through a body lumen, the implant disposed on the catheter. 
     
     
         127 . The method of  claim 122 , wherein the implant temperature is raised to a temperature in the range from about 38° C. to about 60° C. 
     
     
         128 . The method of  claim 122 , wherein the implant is a stent. 
     
     
         129 . The method of  claim 122 , further comprising implanting the implant into a breast. 
     
     
         130 . The method of  claim 122 , further comprising excluding an aneurysm with the implant. 
     
     
         131 . The method of  claim 122 , wherein the implant is an orthopedic implant. 
     
     
         132 . The method of  claim 122 , wherein the particles are nanoparticles. 
     
     
         133 . The method of  claim 122 , wherein the particles are nanoshells. 
     
     
         134 . The method of  claim 133 , wherein the nanoshells comprise a non-conducting core layer and a conducting outer shell layer. 
     
     
         135 . The method of  claim 122 , wherein the electromagnetic radiation is one of ultraviolet, visible, near infrared and infrared light. 
     
     
         136 . The method of  claim 122 , wherein exposing the implant to electromagnetic radiation comprises exposing the implant to electromagnetic radiation extracorporally. 
     
     
         137 . The method of  claim 122 , wherein exposing the implant to electromagnetic radiation comprises exposing the implant to electromagnetic radiation from within the body. 
     
     
         138 . The method of  claim 122 , wherein exposing the implant to electromagnetic radiation comprises delivering electromagnetic radiation to the implant with a catheter. 
     
     
         139 . The method of  claim 122 , wherein exposing the implant to electromagnetic radiation comprises delivering the radiation for a fixed duration of time. 
     
     
         140 . The method of  claim 122 , wherein exposing the implant to electromagnetic radiation comprises delivering the radiation until a desired temperature is obtained in the implant. 
     
     
         141 . The method of  claim 122 , wherein exposing the implant to electromagnetic radiation comprises delivering the radiation over periodic intervals. 
     
     
         142 . The method of  claim 122 , wherein exposing the implant to electromagnetic radiation comprises delivering the radiation continuously during a defined period. 
     
     
         143 . The method of  claim 122 , wherein the implant is biodegradable. 
     
     
         144 . The method of  claim 122 , further comprising releasing a therapeutic agent from the implant in a controlled manner. 
     
     
         145 . The method of  claim 144 , wherein the therapeutic agent inhibits restenosis. 
     
     
         146 . The method of  claim 144 , wherein the therapeutic agent comprises at least one of antibiotics, thrombolytics, anti-thrombotics, anti-inflammatories, cytotoxic agents, anti-proliferative agents, vasodilators, gene therapy agents, radioactive agents, immunosuppressants, chemotherapeutics, endothelial cell attractors, endothelial cell promoters, stem cells and combinations thereof. 
     
     
         147 . A method of controlling degradation of an implant, the method comprising:
 providing a biodegradable implant having a plurality of particles dispersed therein and wherein the implant degrades at a first rate when implanted in tissue at normal body temperature; and   exposing the implant to electromagnetic radiation, the incident radiation being converted into heat energy thus raising the temperature of the implant above normal body temperature, thereby changing the biodegradation rate of the implant relative to the first rate.   
     
     
         148 . The method of  claim 147 , further comprising discontinuing exposure of the implant to the electromagnetic radiation thereby allowing the implant to cool down so that it returns to body temperature. 
     
     
         149 . The method of  claim 147 , further comprising monitoring the temperature of the implant. 
     
     
         150 . The method of  claim 147 , wherein the implant temperature is raised to a temperature in the range from about 38° C. to about 60° C. 
     
     
         151 . The method of  claim 147 , wherein the implant is a stent. 
     
     
         152 . The method of  claim 147 , further comprising implanting the implant into a breast. 
     
     
         153 . The method of  claim 147 , further comprising excluding an aneurysm with the implant. 
     
     
         154 . The method of  claim 147 , wherein the implant is an orthopedic implant. 
     
     
         155 . The method of  claim 147 , wherein the particles comprise nanoparticles. 
     
     
         156 . The method of  claim 147 , wherein the particles comprise nanoshells. 
     
     
         157 . The method of  claim 147 , wherein the particles comprise a non-conducting core layer and a conducting outer shell layer adjacent to the core layer. 
     
     
         158 . The method of  claim 147 , wherein the electromagnetic radiation is one of ultraviolet, visible, near infrared and infrared light. 
     
     
         159 . The method of  claim 147 , wherein exposing the implant to electromagnetic radiation comprises exposing the implant to electromagnetic radiation extracorporally. 
     
     
         160 . The method of  claim 147 , wherein exposing the implant to electromagnetic radiation comprises exposing the implant to electromagnetic radiation from within the body. 
     
     
         161 . The method of  claim 147 , wherein exposing the implant to electromagnetic radiation comprises delivering electromagnetic radiation to the implant with a catheter. 
     
     
         162 . The method of  claim 147 , wherein exposing the implant to electromagnetic radiation comprises delivering the radiation for a fixed duration of time. 
     
     
         163 . The method of  claim 147 , wherein exposing the implant to electromagnetic radiation comprises delivering the radiation until a desired temperature is obtained in the implant. 
     
     
         164 . The method of  claim 147 , wherein exposing the implant to electromagnetic radiation comprises delivering the radiation over periodic intervals. 
     
     
         165 . The method of  claim 147 , wherein exposing the implant to electromagnetic radiation comprises delivering the radiation continuously during a defined period. 
     
     
         166 . The method of  claim 147 , wherein exposing the implant comprises irradiating a carrier containing a reagent, the carrier releasing the reagent and wherein the reagent reacts with the implant to degrade it. 
     
     
         167 . The method of  claim 166 , wherein the reagent is an enzyme. 
     
     
         168 . The method of  claim 166 , wherein the reagent is a catalyst. 
     
     
         169 . The method of  claim 147 , further comprising releasing a therapeutic agent from the implant in a controlled manner. 
     
     
         170 . The method of  claim 169 , wherein the therapeutic agent inhibits restenosis. 
     
     
         171 . The method of  claim 169 , wherein the therapeutic agent comprises at least one of antibiotics, thrombolytics, anti-thrombotics, anti-inflammatories, cytotoxic agents, anti-proliferative agents, vasodilators, gene therapy agents, radioactive agents, immunosuppressants, chemotherapeutics, endothelial cell attractors, endothelial cell promoters, stem cells and combinations thereof.