the scpc is prepared by forming an aqueous or non - aqueous paste of a sufficient amount of an organic or inorganic silica salt such as sodium silicate to provide between about 0 . 31 mole and about 0 . 93 mole of silica in the thermally treated composite and calcium phosphate such as bicalcium phosphate . in the alternative , an alkali metal oxide such as sodium oxide may be included in a mixture comprising silica in place of the sodium silicate . the paste may be pressed into pellets for more convenient handling . it will be understood that the silicate salt and calcium phosphate may be mixed as a dry powder with good results . the mixture , be it in the form of pellets or other formed shape or as a dried powder , is sintered at temperatures ranging from about 130 ° c . to about 1200 ° c . the composition of the samples after thermal treatment , shown in table 1 below , was determined by x - ray diffraction analysis and scanning electron microscopy . the relatively high molar concentration of silica that derived from a silica salt causes a shift in the 20 in the position of the characteristic signals of the silica and calcium phosphate phases and is indicative of the silicate - phosphate ion substitution . the ion substitution exchange resulted in significant decrease in the crystallization temperature in both the silica and calcium phosphate phases . for example as shown in the table , cristobalite , which normally is formed when low quartz is heated to around 720 ° c ., was formed in the phase composition of the composite at the lower temperature of 690 ° c . the formation of these crystalline phases at lower temperature increased the bioactivity of the scpc . following thermal treatment , the scpc material is ready for use such as by forming granules into a desired shape , such as a block , sphere or sheet or application of a layer of the composite over at least a portion of a suitable prosthesis for implant . for example , the composite can be deposited as a layer on a device such as a pin for insertion in the bone being repaired . in addition the composite may be applied directly to bone being repaired . as mentioned above , it is highly preferred that the bioactive composite be porous . good results can be achieved when porosity ranges from 10 vol % to about 80 vol %. for the higher porosities it is preferred to include a suitable pore former such as a fugitive material that is consumed during the thermal treatment process . likewise , pore formation can be initiated in the raw composite mix by including a foaming agent or a fugitive solvent . pore forming and fugitive agents for use in ceramic composites are well known and are commercially available and the selection of a suitable agent is clearly understood . in many cases the solvent of the composite paste will itself form pores in sufficient number and size as it leaves the paste during thermal treatment . it is preferred that the pores be less than 800 μm to aid in maintaining the structural integrity of the finished composite . the bioactive composite may have a pore size of between about 0 . 1 μm to about 500 μm and good results are achieved with pore sizes ranging from about 10 μm to about 300 μm the composites of table 1 were tested for adsorption of serum protein , a necessary first step to the production of new bone growth around the scpc , and it was found that protein adsorption varied with the sintering temperature which the material was pretreated at during processing . it was found that protein adsorption dropped as the sintering temperature was increased to about 690 ° c . and thereafter sharply increased between 690 ° c . and 800 ° c . although it is not fully understood , this may be attributed to the transformation of silica from amorphous phase to a crystalline phase which may inhibit protein adsorption onto the surface of the scpc thermally treated at the lower temperature below 690 ° c . however , the silica is transformed from l - quartz into α - cristobalite ( after thermal treatment above 690 ° c .) which is associated with a significant increase in serum protein adsorption . in addition , the formation of β - nacapo 4 which also begins forming at about 690 ° c . and increases as the treatment temperature increases above about 690 ° c . is also associated with a significant increase in serum protein adsorption . regardless of the thermal treatment , however , the scpc of the present invention absorbs more protein than the standard bioactive glass alone . also , the disruption of the structure of the scpc caused by the exchange of silica in the calcium phosphate phase and the exchange of phosphate into the silica phase improves protein adsorption . scpcs , identified in table 1 as c3s1 , c1s1 and c1s3 were sintered at temperatures ranging between 355 ° c . and 800 ° c . the phase compositions at several sintering temperatures have been determined and are set out in table 1 . the compositions were tested for protein absorption as reported by ahmed , el - ghannam and fouda , biomaterials forum , 27 th annual meeting transactions , 23 , may - jun . 2001 in the following manner . particles ( 90 - 250 μm ) from each of the samples were separately immersed in a simulated body fluid comprising fetal bovine serum for 3 hours at 37 ° c . after immersion the protein was extracted using 1 % sds . protein concentration was determined using a gold staining dot block technique . for a comparison , a control experiment using bioactive glass particles of the same particle size range was run in parallel . after the samples were cooled down to room temperature they were immersed in protein solution . the adsorbed protein was determined as described above . samples containing α - cristobalite and β - nacapo 4 adsorbed statistically significant higher amounts of serum protein than samples containing l - quartz and pyrophosphate . as the amount of the cristobalite increased the adsorption of protein increased . the following example illustrates the effect on bone tissue regeneration by the resorbable bioactive scpc of the present invention . samples prepared as described above and identified in table 1 above as c1s1 and c1s3 and thermally treated at 690 ° c . were analyzed along with a control consisting of a commercially available bioglass were evaluated for bone tissue response in the following manner . a rabbit femur model was used to evaluate bone tissue response to the new material . nine ( 9 ) rabbits 3 - 4 months weighing about 3 kg were used . a critical size bone defect ( 7 mm in diameter ) was created in the cortical bone of each femur . granules of c1s3 and c1s1 as well as the control bioglass were used separately in sufficient amount to fill the defects . the animals were sacrificed after 3 weeks . bone segments containing the defects were fixed , dehydrated , decalcified , sliced into thin sections ( 5 - 7 micron ) and stained with h & amp ; e . scanning electron microscopic analysis of the c1s3 particles showed a pore size ranging from 10 - 300 μm . measurements of porosity using mercury intrusion method showed that the particles acquired 54 % porosity . the pore size is large enough to allow for bone cell colonization and vascularization of the newly formed bone . the high porosity percent provides high surface area for bone cell attachment and stimulation of bone bioactivity reactions that results in bone formation . moreover , the porosity regulates graft material resorption during new bone tissue formation . fig1 , 2 and 3 show the histological evaluations of critical size bone defects , created in the cortical bone of the femora of new zealand rabbits that were grafted with particles ( 150 - 600 μm ) of c1s3 ( fig1 ), c1s1 ( fig2 ), both sintered at 690 ° c ., and bioactive glass ( fig3 ), the compositions of which are shown in table 1 above . after 3 weeks , defects grafted with c1s3 were almost completely filled with new bone ( fig1 ). bone formed in the internal side of the defect has been completely remodeled and few vascular cavities remained . the bone defect treated with composition c1s1 ( fig2 ) also showed substantial development of new bone tissue . the defect treated with bioactive glass ( bg ) alone ( fig3 ) exhibited less new bone tissue and a considerable amount of bg is observed filling the marrow cavity and the defect itself . these results indicate that scpcs containing a high silica concentration not only have strong stimulatory effects on bone cell function but also resorb in harmony with the new bone tissue formation . new bone is also present within the marrow cavity that was initially filled with graft material . the architecture of the remodeled cortical bone and marrow resembles that of normal healthy bone . this indicates that the composition of the present invention , particularly the c1s3 material , has a strong stimulatory effect on stem cell differentiation into osteoblasts and can be used as a delivery system for mesnechymal stem cells . edx analysis of the new bone that formed inside the defect indicates that it is mineralized bone with a ca / p ratio of 1 . 65 . on the other hand , defects grafted with bg were filled with a substantial quantity of graft materials in addition to bone . it is interesting to note that new bone tissue formed not only on the outer surfaces of c1s1 particles but also inside the pores of the particulates . these results clearly demonstrate that the porous scpc of the present invention is highly bioactive in that it has a strong stimulatory effect on bone cell attachment , proliferation , differentiation and bone tissue regeneration . the foregoing example is by way illustration only and should not be taken as limiting the invention . although preferred embodiments have been described herein in detail , it is understood by those skilled in the art that variations may be made thereto without departing from the spirit and scope of the invention as defined by the claims appended hereto .
a method is disclosed for the generation of bone tissue by the preparation and the application to bone defect sites of a resorbable silica - calcium phosphate bioactive composite that finds utility as a bone tissue engineering scaffold . the resorbable silica - calcium phosphate bioactive composite can be applied directly to bone defect or can be employed as a bioactive coating on implants to facilitate bone growth around the implant . the resorbable silica - calcium phosphate bioactive composite is prepared from a mixture of a silica salt in an amount to provide between about 0 . 31 moles and about 0 . 93 moles of silica and calcium phosphate , said silica salt being present in the resorbable silica - calcium phosphate bioactive composite . the mixture is thermally treated at a temperature ranging between about 130 ° c . to about 1200 ° c . to form said resorbable silica - calcium phosphate bioactive composite having a phase composition comprising a thermally treated form of silica and calcium phosphate .