Medical device for bone implant and method for producing such device

Abstract

A bone implantable medical device made from a biocompatible material, preferably comprising titania or zirconia, has at least a portion of its surface modified to facilitate improved integration with bone. The implantable device may incorporate a surface infused with osteoinductive agent and/or may incorporate holes loaded with a therapeutic agent. The infused surface and/or the holes may be patterned to determine the distribution of and amount of osteoinductive agent and/or therapeutic agent incorporated. The rate of release or elution profile of the therapeutic agent may be controlled. Methods for producing such a bone implantable medical device are also disclosed and employ the use of ion beam irradiation, preferably gas cluster ion beam irradiation for improving bone integration.

1 . A method of modifying a surface of bone-implantable medical device comprising the steps of:
 coating at least a first portion of the surface of the medical device with an osteoinductive agent to form a coated surface region; and   first irradiating at least a portion of the coated surface region with a first ion beam.   
   
   
       2 . The method of  claim 1 , wherein the first irradiating step forms a shallow surface and subsurface layer comprising embedded molecules and/or dissociation products of the osteoinductive agent. 
   
   
       3 . The method of  claim 2 , wherein the first ion beam is a first gas cluster ion beam and further wherein the shallow surface and subsurface layer is an infused surface layer. 
   
   
       4 . The method of  claim 1 , wherein the osteoinductive agent comprises, separately or in combination, any of the materials from the group consisting of: a nutrient material, tricalcium phosphate, hydroxyapatite, Bioglass 45S5, Bioglass 58S, a bone growth-stimulating agent, a growth factor, a cytokine, a TGF-β protein, a BMP, a GPI-anchored signaling protein, an RGM, and a growth regulatory protein. 
   
   
       5 . The method of  claim 1 , wherein the surface of the bone-implantable medical device comprises, separately or in combination, any of a metal, an oxide, or a ceramic. 
   
   
       6 . The method of  claim 5 , wherein the surface comprises titanium, titania, or zirconia. 
   
   
       7 . The method of  claim 1 , further comprising the steps, prior to the coating step:
 forming a second ion beam that is a gas cluster ion beam; and   second irradiating at least a second portion of the surface of the medical device to clean the at least a second portion of the surface.   
   
   
       8 . The method of  claim 1 , wherein the first irradiating step further comprises employing a mask to control the at least a portion of the coated surface region that is irradiated. 
   
   
       9 . The method of  claim 1 , wherein the first irradiating step further comprises directing the first ion beam to control the at least a portion of the coated surface region that is irradiated. 
   
   
       10 . The method of  claim 1 , further comprising the steps of:
 forming one or more holes in the surface of the medical device;   loading at least one of the one or more holes with a therapeutic agent; and   third irradiating an exposed surface of the therapeutic agent in at least one loaded hole with a third ion beam to form a barrier layer at the exposed surface.   
   
   
       11 . The method of  claim 10 , wherein the third ion beam is a gas cluster ion beam. 
   
   
       12 . The method of  claim 10 , wherein the barrier layer controls an elution rate of therapeutic agent. 
   
   
       13 . The method of  claim 10 , wherein the barrier layer controls a rate of inward diffusion of a fluid into the hole. 
   
   
       14 . A method of modifying a surface of bone-implantable medical device comprising the steps of:
 forming one or more holes in the surface of the medical device;   first loading at least one of the one or more holes with a first therapeutic agent; and   first irradiating an exposed surface of the first therapeutic agent in at least one loaded hole with a first ion beam to form a first barrier layer at the exposed surface in the at least one loaded hole.   
   
   
       15 . The method of  claim 14 , wherein the one or more holes are disposed on the surface in a predetermined pattern to distribute the first therapeutic agent on the surface according to a predetermined distribution plan. 
   
   
       16 . The method of  claim 14 , wherein there are at least two holes, one or more of the holes with a first therapeutic agent and one or more holes loaded with a second therapeutic agent different from the first therapeutic agent. 
   
   
       17 . The method of  claim 15 , wherein at least one of the one or more holes is loaded with a first quantity of the first therapeutic agent that differs from a second quantity of the first therapeutic agent loaded in at least another of the one or more holes. 
   
   
       18 . The method of  claim 14 , wherein the first loading step does not completely fill the at least one hole, and following the first irradiating step further comprising the steps of:
 second loading the at least one incompletely filled hole with a further therapeutic agent overlying the first barrier layer; and   second irradiating an exposed surface of the further therapeutic agent in at least one second loaded hole with a second ion beam to form a second barrier layer at the exposed surface in the at least one loaded hole.   
   
   
       19 . The method of  claim 18 , wherein the first barrier layer and the further barrier layer have different properties for controlling elution rate of the first and second therapeutic agents. 
   
   
       20 . The method of  claim 14 , wherein the first ion beam is a first gas cluster ion beam. 
   
   
       21 . The method of  claim 18 , wherein the first ion beam is a first gas cluster in beam and further wherein the second ion beam is a second gas cluster ion beam. 
   
   
       22 . A bone-implantable medical device having a surface, wherein at least a portion of the surface comprises a shallow layer comprising molecules and/or dissociation products of an osteoinductive agent embedded into the at least a portion of the surface. 
   
   
       23 . The medical device of  claim 22 , wherein the shallow layer is a GCIB infused surface layer. 
   
   
       24 . The medical device of  claim 23 , wherein the surface of the medical device comprises a material selected from the group consisting of titanium, titania, and zirconia. 
   
   
       25 . The medical device of  claim 23 , further comprising:
 one or more holes containing a therapeutic agent in the surface of the medical device; and   at least one or more barrier layers at one or more surfaces of the therapeutic agent contained in the one or more holes; wherein   the at least one or more barrier layers constructed to control at least one elution rate of therapeutic agent.   
   
   
       26 . A bone-implantable medical device having a surface, wherein at least a portion of the surface comprises:
 one or more holes containing a therapeutic agent in the surface of the medical device; and   at least one or more barrier layers at one or more surfaces of the therapeutic agent contained in the one or more holes; wherein   the at least one or more barrier layers control at least one elution rate of therapeutic agent.   
   
   
       27 . The medical device of  claim 26 , wherein the surface of the medical device comprises a material selected from the group consisting of titanium, titania, and zirconia. 
   
   
       28 . The medical device of  claim 26 , wherein the one or more holes one are disposed on the surface in a predetermined pattern to distribute the therapeutic agent on the surface according to a predetermined distribution plan.