Abstract:
A bioactive composite includes 10% to 40% by weight of calcium sulfate (CaSO 4 ), 10% to 20% by weight of tantalum pentoxide (Ta 2 O 5 ), and 40% to 80% of polyetheretherketone (PEEK). Calcium sulfate is anhydrous calcium made by removing crystallization water of beta calcium sulfate hemihydrate.

Description:
BACKGROUND OF THE INVENTION 
     1. Technical Field 
       [0001]    The present invention relates to a bioactive composite, and more particularly to a bioactive composite with function of radiopacity for surgery. 
       2. Description of Related Art 
       [0002]    As high development of theory and technique of manufacturing and biomaterial usage in recent years, titanium and titanium alloys are replaced by high-performance biopolymers in surgical implants. For a variety of biopolymer materials today, polyetheretherketone (PEEK) has an elastic modulus relatively close to that of human bones, so that when it is implanted, it could reduce bone resorption and bone atrophy caused by stress shielding in biomechanics. Furthermore, PEEK has the functions of chemical resistance, fatigue resistance, stable physicochemical property to take sterilization operation by autoclaving, ethylene oxide, or gamma radiation, so that PEEK is a good long term implant (Biomaterials 2007, 28:4845-4869). However, PEEK has a weak link with human bones due to its low bioactivity. 
         [0003]    According to biomimetics of bone bioengineering, pore size and porosity of the implants affect cell adhesion and bone ingrowth. The interconnected pores benefit ingrowth of blood vessels and metabolism. However, porous scaffolds usually reveal the following properties: inorganic porous scaffolds are brittle and biopolymer porous scaffolds have weak strength. Therefore, porous bone implanting scaffolds are insufficient to provide the trauma tissues a stable mechanical environment when they are used for the treatment of degenerative disease of lumbar spine or cervical spine. 
         [0004]    Another problems of PEEK are its lack of bioactive and radio translucency which makes it can&#39;t be shown in X-ray film. All these problems should be fixed. 
       BRIEF SUMMARY OF THE INVENTION 
       [0005]    In view of the above, the primary objective of the present invention is to provide a bioactive composite with functions of radiopacity and in site pore forming after implanting in tissues. 
         [0006]    In order to achieve the objective of the present invention, a bioactive composite includes 10% to 40% by weight of calcium sulfate (CaSO 4 ), 10% to 20% by weight of tantalum pentoxide (Ta 2 O 5 ), and 40% to 80% of polyetheretherketone (PEEK). Anhydrous calcium sulfate is made by removing moisture from beta calcium sulfate hemihydrate. 
         [0007]    In an embodiment, the further bioactive composite includes up to 10% by weight of barium sulfate (BaSO 4 ). 
         [0008]    In an embodiment, the further bioactive composite includes up to 10% by weight of ferrous ferric oxide (Fe 3 O 4 ). 
         [0009]    The bioactive composite of the present invention has the function of radiopacity, and overcoming the problems of the conventional PEEK implants. 
     
    
     
       BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS 
         [0010]    The present invention will be best understood by referring to the following detailed description of some illustrative embodiments in conjunction with the accompanying drawings, in which 
           [0011]      FIG. 1  is a flowchart of the manufacturing and testing processes of a preferred embodiment of the present invention; 
           [0012]      FIG. 2A  is a diagram of the preferred embodiment of the present invention, showing the sizes of the bioactive composites (calcium sulfate); 
           [0013]      FIG. 2B  is sketch diagram of the preferred embodiment of the present invention, showing how the bioactive composite forming the pores after being implanted; 
           [0014]      FIG. 3  is a sketch diagram of the preferred embodiment of the present invention, showing the reference gray scale relating to the thicknesses of aluminum corresponding to the X-ray radiopacity; 
           [0015]      FIG. 4  is a sketch diagram of the preferred embodiment of the present invention, showing the X-ray radiopacity of ten composites with different compositions; 
           [0016]      FIG. 5A  is a sketch diagram of the preferred embodiment of the present invention, showing the melting temperatures (T m ) of the ten composites with different compositions; 
           [0017]      FIG. 5B  is a sketch diagram of the preferred embodiment of the present invention, showing the crystallization temperatures (T c ) of the ten composites with different compositions; 
           [0018]      FIG. 5C  is a sketch diagram of the preferred embodiment of the present invention, showing the measurement results of the DSC (differential scanning calorimeter); 
           [0019]      FIG. 6  is a sketch diagram of the preferred embodiment of the present invention, showing the TGA (thermogravimetric analysis) of the ten composites with different compositions; and 
           [0020]      FIG. 7  is a sketch diagram of the preferred embodiment of the present invention, showing the biological compatibility of the ten composites with different compositions. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0021]    In the preferred embodiment of the present invention, we provide ten bioactive composites with different compositions, named a first composite, a second composite, . . . to a tenth composite, and the compositions of the composites are listed in the Table 1. 
         [0000]    
       
         
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 1 
               
               
                   
               
               
                   
                   
                   
                   
                   
                 PEEK 
               
               
                 composite 
                 CaSO 4  (%) 
                 Ta 2 O 5  (%) 
                 BaSO 4  (%) 
                 Fe 3 O 4  (%) 
                 (%) 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 1 
                 10 
                   
                   
                   
                 90 
               
               
                 2 
                 10 
                 10 
                   
                   
                 80 
               
               
                 3 
                 20 
                   
                   
                   
                 80 
               
               
                 4 
                 20 
                 10 
                   
                   
                 70 
               
               
                 5 
                 30 
                   
                   
                   
                 70 
               
               
                 6 
                 30 
                 10 
                   
                   
                 60 
               
               
                 7 
                 40 
                   
                   
                   
                 60 
               
               
                 8 
                 20 
                 20 
                   
                   
                 60 
               
               
                 9 
                 10 
                   
                 10 
                   
                 80 
               
               
                 10 
                 10 
                   
                   
                 10 
                 80 
               
               
                   
               
             
          
         
       
     
         [0022]      FIG. 1  shows a flowchart of manufacturing and testing processes of the bioactive composite of the preferred embodiment of the present invention. All the ten composites as described above have polyetheretherketone (PEEK). In the manufacture process, technical grade PEEK is selected and purified, and then is mixed with calcium sulfate (CaSO 4 ) bioceramics and tantalum pentoxide (Ta 2 O 5 ), which is a radiopacity material. Next, we take some tests to test the composites whether they are the materials for surgery implants, which includes 1) functional test (for radiopacity); 2) physicochemical property test (thermal analysis (T g /T m ), FT-IR, and XRD); 3) mechanical property test (compression strength); and 4) ISO 10993-5 MC3T3-E1 cell test. The results of the tests 1), 2), and 3) are described hereafter. 
         [0023]      FIG. 2A  shows various phases of calcium sulfate (CaSO 4 ) and manufacture conditions, and  FIG. 2B  shows that bioactive is increasing when calcium sulfate (CaSO 4 ), which has high solubility, is implanted in human body in the beginning, and then calcium sulfate (CaSO 4 ) will be dissolved to form a porous structure, which form porous scaffolds. The chemical reaction is: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0024]    As shown in  FIG. 2A , calcium sulfate (CaSO 4 ) has calcium sulfate dehydrate, alpha calcium sulfate hemihydrate, beta calcium sulfate hemihydrate, and anhydrous calcium sulfate. Moisture content of calcium sulfate will be volatized in the manufacture process, which causes the composites degrading. Therefore, smaller size benefits the process, and gets more uniform composite. In the present embodiment, the crystallization water in the beta calcium sulfate hemihydrate is removed to get anhydrous calcium sulfate. The anhydrous calcium sulfate is selected to be mixed with PEEK. 
         [0025]    Furthermore, since calcium sulfate is hydrolysable, it could hydrolyze to form the composite of the present invention automatically when put it in human body. Besides, it will form pores when it is put in human body for a long time ( FIG. 2B ). When the composite of the present invention is applied to be implants inserted into intervertebral of human&#39;s spine, the implants must have sufficient strength to take the stress of a wide range of motion of spine. Calcium sulfate makes the composite of the present invention have such property. 
         [0026]    In order to apply the composite of the present invention to be surgical implants, the composite satisfies Standard Specification for Polyetheretherketone (PEEK) Polymers for Surgical Implant Applications of American Society for Testing and Materials (ASTM F2026-10), and the requirements are listed in Table 2. 
         [0000]    
       
         
               
               
               
             
           
               
                 TABLE 2 
               
               
                   
               
               
                 Parameters 
                 Method 
                 Requirement 
               
               
                   
               
             
             
               
                 T g  (° C.) 
                 DSC, 20° C./min, sealed sample, 
                 125-165 
               
               
                   
                 T g  taken from second reheat 
               
               
                 T m  (° C.) 
                 DSC, 20° C./min, sealed sample, 
                 320-360 
               
               
                   
                 T m  taken as max. point on reheat 
               
               
                   
                 exotherm 
               
               
                 T c  (° C.) 
                 DSC, 20° C./min, sealed sample, 
                 260-320 
               
               
                   
                 T c  taken as max. point on 
               
               
                   
                 cooling endotherm 
               
               
                 Viscosity 
                 Per 5.3 as agreed 
                 As agreed 
               
               
                 Infrared spectrometer 
                   
                 per 5.1 
               
               
                 Total heavy metal as 
                 U.S. Pharmacopeia Test 231 
                 &lt;0.1 
               
               
                 lead. Max. % 
               
               
                   
               
             
          
         
       
     
         [0027]      FIG. 5A  and  FIG. 5B  show the melting temperature (T m ) and crystallization temperatures (T c ) of the ten composites provided by the present preferred embodiment, which are test by a differential scanning calorimetry (DSC). The principle of DSC is to measure the thermal energy to keep the temperature of the sample constant when the sample absorb or release heat due to phase transition, glass transition, and chemical reaction. 
         [0028]    Typically, the reactions of polymer are shown in following table. 
         [0000]    
       
         
               
               
             
           
               
                   
               
             
             
               
                 No phase 
                 Keep the temperature of the sample the same as reference by 
               
               
                 transition and 
                 overcome the difference of specific heat between them to show the 
               
               
                 other reaction 
                 standard line of DSC. In order to make sure the consistence of the 
               
               
                   
                 standard line, the reference must have no chemical reaction in the 
               
               
                   
                 experience temperature range, and have a constant specific heat. 
               
               
                 Glass transition 
                 When polymer approaches the glass transition temperature, heat 
               
               
                   
                 capacity increases, it needs more heat to maintain the temperature, 
               
               
                   
                 so the standard line of DSC usually changes. 
               
               
                 Crystallization 
                 Amorphous polymer, which is formed in cooling process, will 
               
               
                   
                 crystalize when heating, and release crystallization heat. It must 
               
               
                   
                 reduce the heat flow to keep the temperature constant, so the DSC 
               
               
                   
                 has a heat release peak. 
               
               
                 Melting 
                 As the temperature raising, the crystalized part starts to melt, the 
               
               
                   
                 compensator found that it has to increase the heat flow to keep the 
               
               
                   
                 temperature, so a heat absorption peak generates. 
               
               
                 Oxidation and 
                 Some polymer has oxidation and crosslinking in high temperature, 
               
               
                 crosslinking 
                 so DSC line will have a heat release peak. 
               
               
                 Decomposition 
                 When the temperature is higher than a predetermined temperature, 
               
               
                   
                 polymer chains break down, and a heat absorption peak appears. 
               
               
                   
               
             
          
         
       
     
         [0029]    It is noted that glass transition temperature (T g ) is one of transition temperatures. Polymer will be transformed from a rubber type in high temperature into a glass type (hard and brittle) in low temperature. 
         [0030]      FIG. 5C  is the typical DSC thermograms showing the characteristic melting temperature (T m ) and glass transition temperature (T g ). Melting temperature (T m ), usually associating with processing temperature, is the temperature of the crystalline part of polymer breaking down by heat. Crystalline plastic has a significant melting temperature. In solid type, it has a regular molecular arrangement, higher strength and tensile stress, specific volume change a lot when it is molten, large shrinkage when it is solidified, internal stress can&#39;t be released easily, product is opaque, low heat dissipation, large shrinkage in cooling molding, and small shrinkage in hot molding. Amorphous plastic has no significant melting temperature. In solid type, it has an irregular molecular arrangement, little change of specific volume when it is molten, little shrinkage when it is solidified, product is transparent, color change into yellow when temperature is high, and has high heat dissipation. 
         [0031]    As the discussion above, the ten composites of the preferred embodiment of the present invention includes the following specifications: crystallization temperatures (T c ) is between 330° C. and 333° C.; glass transition temperature (T g ) is 152° C.; and melting temperature (T m ) is between 368° C. and 370° C. The results show that all the composites of the preferred embodiment of the present invention satisfy ASTM F2026-10. 
         [0032]      FIG. 6  shows the results of thermogravimetric analysis (TGA) of the ten composites of the preferred embodiment of the present invention. TGA measures a weight difference of a sample in a predetermined temperature. A sample is placed on a temperature-controllable heater. A predetermined gas, such as nitrogen and oxygen, is provided. The weight loss of the sample is recorded by temperature or by time to determine some properties of the sample, including degradation temperature, thermal stability, compositions, purity, moisture, reduction temperature, and anti-oxidation. 
         [0033]    The minimum weight that TGA could measure is 0.1 μg, so the carriers should be received in a sealed chamber to prevent interference of air ventilation. The gas flow is limited for not to interfere the system. 
         [0034]    TGA may set different temperatures. It could solve the problem of a sample having different decomposition rates, and making the products of decomposition overlap. In TGA, we may provide a constant temperature for the first stage reaction, and then raising the temperature to another constant temperature for the second stage reaction when the first stage reaction is totally completed that could obtain precise weight loss data. 
         [0035]      FIG. 6  shows the results of TGA of the ten composites of the preferred embodiment of the present invention. It shows that a temperature range is between 570° C. and 590° C. for 10% weight loss. 
         [0036]      FIG. 3  is the reference gray scale relating to the thicknesses of aluminum corresponding to the X-ray radiopacity, and  FIG. 4  is the gray scale of X-ray radiopacity of the ten composites of the preferred embodiment of the present invention. It shows that the radiopacity of the composites with tantalum pentoxide (Ta 2 O 5 ) is better than that without tantalum pentoxide (Ta 2 O 5 ), and the content of tantalum pentoxide (Ta 2 O 5 ) is positive proportional to the radiopacity. The data are shown in Table 4.  FIG. 4  also shows the ninth composite and the tenth composite having the most suitable radiopacity. Therefore, tantalum pentoxide (Ta 2 O 5 ), ferrous ferric oxide (Fe 3 O 4 ), and barium sulfate (BaSO 4 ) are the best additives of PEEK. 
         [0000]    
       
         
               
               
               
             
           
               
                   
                 TABLE 4 
               
               
                   
                   
               
               
                   
                 Group (N = 3) 
                 Al step-wedge (mm) 
               
               
                   
                   
               
             
             
               
                   
                 CaSO 4  20% 
                 0.00 
               
               
                   
                 CaSO 4  20% + Ta 2 O 5  20% 
                 1.22 ± 0.04 
               
               
                   
                 CaSO 4  30% + Ta 2 O 5  10% 
                 1.14 ± 0.05 
               
               
                   
                 CaSO 4  20% + Ta 2 O 5  10% 
                 1.18 ± 0.01 
               
               
                   
                   
               
             
          
         
       
     
         [0037]      FIG. 7  is the biological compatibility of the ten composites of the preferred embodiment of the present invention and three control groups. The control groups include neat PEEK, positive control, and negative control. The data are shown in Table 5. 
         [0000]    
       
         
               
               
               
               
               
               
             
               
               
               
               
               
               
             
               
               
             
           
               
                 TABLE 5 
               
               
                   
               
               
                 composite 
                 CaSO 4   
                 Ta 2 O 5   
                 BaSO 4   
                 Fe 3 O 4   
                 PEEK 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 1 
                 10% 
                   
                   
                   
                 90% 
               
               
                 2 
                 10% 
                 10% 
                   
                   
                 80% 
               
               
                 3 
                 20% 
                   
                   
                   
                 80% 
               
               
                 4 
                 20% 
                 10% 
                   
                   
                 70% 
               
               
                 5 
                 30% 
                   
                   
                   
                 70% 
               
               
                 6 
                 30% 
                 10% 
                   
                   
                 60% 
               
               
                 7 
                 40% 
                   
                   
                   
                 60% 
               
               
                 8 
                 20% 
                 20% 
                   
                   
                 60% 
               
               
                 9 
                 10% 
                   
                 10% 
                   
                 80% 
               
               
                 10 
                 10% 
                   
                   
                 10% 
                 80% 
               
             
          
           
               
                 11 
                 Neat PEEK 
               
               
                 12 
                 Positive control 
               
               
                 13 
                 Negative control 
               
               
                   
               
             
          
         
       
     
         [0038]    Positive control: HDPE film extracted with 0.1 g/l ml MEM solution 
         [0039]    Negative control: (0.5% DMSO) 
         [0040]    All the composites pass MC3T3-E1 based cell viability test. 
         [0041]    It must be pointed out that the embodiments described above are only some preferred embodiments of the present invention. All equivalent structures which employ the concepts disclosed in this specification and the appended claims should fall within the scope of the present invention.