Bone cement composition

A bone cement composition has adjustable rheological properties, high strength, and produces a uniform radiological image. The cement is characterized by controlled retention and release of additives incorporated in beads included in the dry component of the cement. The cement comprises beads containing a polymerization initiator in controllable concentrations from 0% to 5% or more by weight. These same beads or others may also contain an opacifier. The polymerization initiator and the opacifier may be selectively distributed throughout the beads or at specific radial locations in the beads. They may also be selectively placed in beads of a particular advantageous size range. Furthermore, in other embodiments of the invention, other advantageous additives can be incorporated in the beads such as dyes, antibiotics, bone growth factors, and other pharmacological or therapeutic agents.

BACKGROUND OF THE INVENTION 
The present invention relates to two-component plastic systems useful for 
surgically filling voids in bones. More specifically, the invention 
relates to polymer cements comprising a liquid component and a dry 
component wherein the dry component includes polymer beads. 
Polymer based surgical cement systems have been successfully employed for 
many years to fill voids in bones. Such cements have found their greatest 
use in the fixation of orthopaedic implants. Typically a bone is cut to 
accommodate an implant and then liquid and dry components of the cement 
system are mixed to form a paste which is applied to the cut bone. The 
implant is seated in this paste, which, when fully polymerized, forms a 
continuous solid interface between the implant and bone. The invention of 
this disclosure encompasses improvements in these polymer bone cements. To 
better understand the invention, it will be helpful to review the basic 
composition, behavior, and deficiencies of prior cements. 
FIG. 1 depicts a typical prior art dry component of a bone cement system. 
The dry component includes a loose mixture of polymer beads 1, polymer 
flakes (or milled beads) 2, and a powdered opacifier 3. The beads contain 
a polymerization initiator such as benzoyl peroxide (BPO). Typically these 
beads are formed in a solution polymerization process in which BPO is 
added as a polymerization initiator to a monomer and polymerization is 
carried out. BPO added in excess of that required for polymerization of 
the monomer remains in the polymer as a residual. The more BPO added, the 
greater will be the residual BPO randomly distributed in the polymerized 
beads, within practical limits. However, the molecular weight of the 
resulting beads decreases as the BPO is increased. A high molecular weight 
is important in bone cement beads because mechanical strength increases as 
molecular weight increases. The tradeoff between residual BPO and 
molecular weight has limited the residual BPO attainable in beads having a 
useful molecular weight. For example, it is very difficult to produce a 
bead with a molecular weight greater than 500,000 and a residual BPO 
content greater than 2% by weight. When the residual BPO content is below 
approximately 1% by weight, the addition of free BPO powder to the mixture 
comprising the dry cement component may be required to achieve a desired 
set time for the bone cement system. Desirable set times are typically 
between 10 and 15 minutes. For example U.S. Pat. Nos. 4,500,658, 4,791,150 
and 4,617,327 teach the addition of free, powdered BPO as a polymerization 
initiator. Uniform dispersion of this BPO powder is difficult. 
The opacifier 3 is included to color the cement to aid its implantation and 
to make it visible on a radiograph. The opacifier tends to form clumps 4 
because it is a fine powder added to the beads and flakes. U.S. Pat. No. 
4,791,150 to Braden et al. and U.S. Pat. No. 4,500,658 to Fox describe 
cements having an opacifier dispersed in polymer cement beads during the 
bead formation. The references teach the use of a suspension 
polymerization batch process for forming beads as discussed above and 
further teach including the opacifier particles in the suspension 
polymerization solution so that the beads formed will contain some 
opacifier. This method of incorporating opacifier is tedious and costly to 
use. It also produces a bead with an uncontrolled and random opacifier 
distribution. 
In use the dry component is mixed with the liquid component which contains 
a monomer and typically an amine accelerator such as 
N,N-Dimethyl-p-toluidine (DMPT). Upon mixing, the monomer dissolves the 
flake polymer to a great extent due to the large surface area of the 
flake, thereby creating a viscous fluid or paste. In addition, the monomer 
begins to dissolve the beads at a much slower rate than the flake because 
of the relatively small surface area of the beads. As the beads partially 
dissolve, residual BPO becomes available to the monomer. The BPO 
decomposes in the presence of DMPT into free radicals which act as 
polymerization initiators for the monomer, and polymer chains begin 
forming from the beads outwardly. However, only the BPO that is exposed by 
bead dissolution is accessible, and the beads only partially dissolve. 
Therefore, since the BPO is distributed throughout the bead, the usable 
BPO concentration of prior art cements is less than the actual 
concentration in the bead. As polymerization progresses, the cement paste 
grows more viscous until it eventually hardens into a solid. It is helpful 
to characterized this hardening process as having three stages. FIG. 2 
depicts a viscosity versus time graph for a typical polymer bone cement. 
This graph depicts the rheological behavior of the cement. During the 
first, or mixing stage, the cement components are mixed and a viscous 
paste, represented by .mu..sub.1, is formed primarily due to the 
dissolution of the polymer flake in the monomer. During the second stage, 
or working time, the paste is of a suitable viscosity to be effectively 
applied to the bone. By design this may be a fairly thick putty-like 
consistency suitable for manually packing into the bone or it may be a 
thinner flowing consistency suitable for injection into the bone. The 
consistency can by controlled, for example, by varying the ratio of flake 
to beads in the dry component. Absent the BPO, this stage would continue 
for a considerable period with only slight thickening due to further 
dissolution of the beads. However, because of the BPO, polymerization 
takes place and the paste reaches a state, represented by .mu..sub.2, 
where it is no longer able to be worked. The polymerization reaction, 
which is exothermic, continues during the final stage until the cement is 
fully randomly distributed within the beads and some of the opacifier 
particles will be located near the bead surface allowing the particles to 
become exposed and separated from the bead when the surface is dissolved 
by the monomer during use. Such separated particles will be deposited in 
the matrix and can form stress concentrators as previously described. 
SUMMARY OF THE INVENTION 
It is therefore an object of the present invention to provide a polymeric 
bone cement composition having a particularly useful viscosity versus time 
curve. 
It is also an object of the present invention to provide a polymeric bone 
cement composition having improved strength due to the reduction of stress 
concentrating structures in the polymerized cement. 
It is a further object of the present invention to provide a polymeric bone 
cement composition having a uniform radiographic image. 
It is also an object of the present invention to provide a polymeric bone 
cement with advantageous additives strategically placed in controlled 
distributions within the cement dry component beads. 
It is also an object of the present invention to provide a polymeric bone 
cement having beneficial additives hardened. The entire process typically 
takes from two to fifteen minutes. Because of the practical limits on the 
amount of residual BPO and its distribution throughout the beads, the 
viscosity versus time curve, as shown in FIG. 2, for prior art cements is 
not readily tailored. 
The resulting solid cement, as depicted in FIG. 3, comprises a matrix of 
polymerized plastic 5 containing a distribution of beads 1 and opacifier 
3. The beads are generally firmly attached to the matrix since the polymer 
chains formed from the beads outwardly as BPO was exposed. However, 
polymerization chains may not form from the beads uniformly if free BPO is 
added to raise BPO levels, as may be necessary when the residual BPO is 
low. In that case the dry cement component contains a non-uniform 
dispersion of BPO powder. When the dry cement component is mixed with the 
liquid cement component, polymerization will proceed more quickly at 
regions of relatively high BPO concentration. These regions will be 
outside of the beads, resulting in localized and less uniform 
polymerization which can result in reduced mechanical properties. 
Also, the opacifier is simply encased in the matrix and forms no attachment 
with it thereby concentrating stresses placed on the cement and weakening 
it. The tendency of the opacifier to clump 4 can further weaken the cement 
and the clumps can obscure the radiographic image of the cement-bone 
interface. Where prior investigators have taught incorporation of the 
opacifier into the beads through solution polymerization, the opacifier 
will be strategically placed in particular advantageously sized cement dry 
component beads. 
It is a still further object of the present invention to provide a method 
of manufacturing a polymeric bone cement composition that enables the 
cement's viscosity versus time curve to be readily adjusted. 
It is finally an object of the present invention to provide a method of 
manufacturing a polymeric bone cement composition that provides for the 
placement of the opacifier and other additives in controlled distributions 
in the cement. 
The above advantageous objects and others are obtained in a cement 
composition characterized by controlled retention and release of additives 
incorporated in beads included in the dry component of the cement. The 
cement composition comprises beads containing a polymerization initiator 
in controllable concentrations from 0% to 5% or more by weight. These same 
beads or others may also contain an opacifier. The polymerization 
initiator and the opacifier may be selectively distributed throughout the 
beads or at specific radial locations in the beads. They may also be 
selectively placed in beads of a particular advantageous size range. 
Furthermore, in other embodiments of the invention, other advantageous 
additives can be incorporated in the beads such as dyes, antibiotics, bone 
growth factors, and other pharmacological or therapeutic agents. Beads 
having the above described structure can be formed using a modified form 
of the microencapsulation technique described in U.S. Pat. No. 4,657,140 
hereby incorporated by reference.

DETAILED DESCRIPTION OF THE INVENTION 
Referring to FIG. 4 a polymer bead 6 has one or more additives distributed 
within it. The present invention provides means for selectively retaining 
an additive within the bead or releasing an additive from the bead. 
Retention and release are controlled in the present invention by the 
selective placement of the additive within the bead at particular 
locations or by the selective placement of the additive in beads of a 
particular size. 
For example, a polymerization initiator 7, preferably benzoyl peroxide 
(BPO), may comprise from 0% to 5% or more of the bead weight. Such beads 
can be combined with other beads of different sizes and compositions to 
form the dry component of a surgical cement system. By incorporating the 
BPO in the beads, the BPO is evenly distributed throughout the cement and 
produces uniform polymerization. The BPO content of the bead 6 can be 
carefully controlled within a wide range using the bead forming process 
discussed later in this specification. The rate of release of the BPO from 
the bead contributes to the rheological behavior of the cement system. 
The bead 6, or another, preferably includes an opacifier 8, such as barium 
sulphate (BaSO.sub.4). By encasing the BaSO.sub.4 within the relatively 
strong bead, the BaSO.sub.4 is prevented from forming a stress 
concentrator in the polymerized cement matrix. Also, the BaSO.sub.4 so 
encased will be uniformly distributed throughout the cement and will 
produce a uniform radiographic image. The retention of the BaSO.sub.4 
within the bead contributes to the strength of the polymerized cement. 
In one embodiment, the cement dry component comprises beads groupable into 
different size ranges corresponding to relatively larger beads and 
relatively smaller beads. Preferably the beads corresponding to the 
different size ranges have different compositions. Upon being mixed with 
the liquid component the smaller beads would dissolve more quickly than 
the larger beads. This would result in any additives contained in the 
smaller beads being released into the cement matrix and any additive 
contained in the larger beads tending to be retained in the larger beads. 
Preferably the smaller beads will completely dissolve before, and thus 
release their additives before, the larger beads dissolve enough to 
release their additives to a significant degree. For example, the 
BaSO.sub.4 is preferably incorporated in beads having a size, or maximum 
dimension, larger than can be dissolved during the working stage so that 
the BaSO.sub.4 is less likely to be freed from the beads and deposited in 
the polymerizing matrix. 
An exemplary cement dry component would contain 85% by weight beads 
containing BaSO.sub.4 and BPO, the beads having an average size of 
approximately 50 .mu.m. The BaSO.sub.4 would be in the form of a fine 
powder comprising particles approximately 1 .mu.m in size and constituting 
approximately 8%-12% of the bead weight. The BASO.sub.4 may form clumps 8 
within the bead 6 as depicted in FIG. 4. The BPO would be in the form of a 
fine powder comprising particles 7 approximately 1 .mu.m in size and 
constituting 2%-3% of the bead weight. The remaining 15% by weight of the 
cement dry component would consist of smaller polymer beads having no 
additives and an approximate average size of 0.1 .mu.m to 10 .mu.m. Upon 
being mixed with the liquid component, the smaller beads would dissolve 
more quickly than the larger beads to form a cement paste. A sufficient 
amount of BPO would be released from the surface of the larger beads to 
cause polymerization of the cement while the larger beads remain 
substantially intact and retain the BaSO.sub.4. 
An alternate exemplary cement dry component would contain 75% by weight 
larger beads containing BPO, 10% by weight larger beads containing 
BaSO.sub.4 and 15% by weight smaller beads containing no additives. This 
alternative composition has manufacturing advantages because only one 
additive is contained in a particular bead type. This makes the 
manufacture of the beads simpler. Also, by having the BaSO.sub.4 and BPO 
in different beads, large quantities of each bead type can be made. Cement 
formulations with different relative percentages of BaSO.sub.4 and BPO can 
then be easily made by mixing different amounts of each bead type. 
However, to take full advantage of the present invention, the BPO 
preferably would all be placed in the smaller beads of the above examples 
so that the BPO is all available to initiate polymerization upon 
dissolution of the smaller beads and before the larger beads dissolve. The 
size of the smaller beads would preferably be adjusted to a size less than 
50 .mu.m to produce the desired release rate of the BPO to obtain a 
desired rheology. For example, a specific amount of BPO contained in very 
small smaller beads would be released more quickly and cause sooner and 
more rapid polymerization than would the same amount of BPO contained in 
larger smaller beads. The larger beads would contain the BaSO.sub.4. The 
size of the larger beads would preferably be greater than or equal to 50 
.mu.m so that they would not dissolve when the smaller beads dissolve. 
Therefore the larger beads will retain the BaSO.sub.4. 
In another embodiment, the placement of additives in beads can be even more 
advantageously effected by placing the additives in strata or layers. FIG. 
5 depicts a bead having layers 9, 10 and 11 and surface 12. It is 
particularly advantageous to place an opacifier at the center of the bead 
and a polymerization initiator located outwardly away from the center. In 
the case of spherical or cylindrical beads for example, the polymerization 
initiator would be located radially outward from the center of the bead. 
By placing the opacifier in the center 11 of the bead, it is well imbedded 
and there is little chance of it being loosely incorporated into the 
matrix of the polymerized cement. By placing the polymerization initiator 
outwardly away from the center of the bead, release of the polymerization 
initiator and thus polymerization will occur before dissolution of the 
bead can release the opacifier from the bead. Selective placement of the 
initiator containing layer and control of the initiator concentration 
allows tailoring of the time of polymerization onset and of the rate of 
polymerization. 
In one embodiment, the polymerization initiator would be placed on the 
surface 12 of the bead. Preferably, all of the polymerization initiator 
contained in the bead would be located at the bead surface. The 
polymerization initiator would all be immediately available to the cement 
mixture to cause polymerization to begin immediately and proceed rapidly 
upon mixing of the dry and liquid cement components. 
In another embodiment, the polymerization initiator would be placed within 
an outer layer of the bead extending from the surface of the bead into the 
bead. The polymerization initiator would become available to the cement 
mixture as this outer layer of the bead dissolves. This more gradual 
release of the polymerization initiator would result in more gradual 
polymerization. 
In yet another embodiment, the polymerization initiator would be placed in 
a layer 10 deeper into the bead with a polymer barrier layer 9 surrounding 
the polymerization initiator containing layer to provide a cement with a 
specific time delay before polymerization begins. This time delay would be 
the time required for the barrier layer 9 to dissolve and expose the 
polymerization initiator containing layer 10. 
Finally, the polymerization initiator could be concentrated in a narrow 
layer in order to produce very rapid polymerization when the layer is 
exposed because a relatively high concentration of polymerization 
initiator would be released over the relatively short period of time 
required to expose all of the narrow layer. Alternatively, the layer could 
be less concentrated or wider to provide more gradual polymerization 
because it would take more time for dissolution of the bead to free the 
polymerization initiator in the wider layer. 
The novel layering of the present invention would enable full utilization 
of all of the BPO contained in the beads since the BPO would be placed in 
the regions of the bead that will be exposed in use. This is an advantage 
over previous cement beads which have a polymerization initiator randomly 
distributed within the beads and therefore only the polymerization 
initiator that by chance lies within the outer regions of the beads which 
are dissolved in use is utilized. 
Such strategic incorporation of additives can yield specific, desirable 
rheological behavior and strength characteristics. Likewise, the above 
structure can advantageously accommodate other additives such as dyes, 
antibiotics, bone growth factors, and other useful agents. 
It is preferable that the polymer or polymer mixture comprising the beads 
be substantially uniform throughout the bead in order to produce a 
substantially homogeneous bead containing additives as so far described. 
In the case of the embodiments having additives in strata, it is 
preferable for the bead to form a structure having a homogeneous 
composition of a polymer or polymer mixture and the additives distributed 
in strata within the homogeneous composition as shown in FIG. 5. The 
additives can be thought of as located in an orbit within the polymer bead 
about the center of the bead. 
According to the present invention the additives can be placed in beads of 
specific sizes, they can be placed singly or in combination with other 
additives, and they can advantageously be placed in strata to achieve 
precise timing and positive encapsulation. All of these structures can be 
produced by modifying the process described in U.S. Pat. No. 4,675,140. In 
this process solid particles or viscous liquid droplets of core material 
are encapsulated in a coating material by feeding a suspension or solution 
of the two materials onto a rotating surface. 
This modified process, as used in the present invention, advantageously 
forms beads from a liquified polymer composition containing a liquified 
polymer and an additive. It is distinguished from other known processes 
which use a polymerization reaction to form beads. By using a liquified 
polymer, a broader range of additives can be incorporated. For example, 
since the polymer is prepolymerized, BPO can be added far in excess of 
that which can be added in a polymerization reaction and without adverse 
impact on the molecular weight of the polymer. Also, the process can be 
controlled to produce a very short dwell time so that the additive is 
subjected to the solvent or heat used to liquify the polymer for a short 
time period. This dwell time can be as short as a few seconds or even 
fractions of a second. Therefore, additives that would otherwise be 
degraded or dissolved by the solvent or heat may be used. In contrast, in 
prior art polymerization reactions, any additives would be exposed to the 
polymerization solution for the entire reaction period which typically can 
be as long as several hours. 
This process also is distinguished from other processes used to form bone 
cement beads containing additives in that it is a continuous process and 
it is capable of forming beads having a wide range of controlled sizes. 
Coated particles and droplets of excess coating material are centrifugally 
thrown from the perimeter of the rotating surface and solidified by 
cooling or evaporation. The excess coating material forms dried droplets 
smaller than the coated particles and can therefore be easily separated 
and recycled. The continuous and controllable nature of the process and 
the ease of separating product from recyclable coating material make the 
process more economical and more efficient than other processes. They also 
make the process applicable where it is desirable to have only coated 
particles in the final product. This process is capable of coating 
particles ranging from 1 .mu.m to 500 .mu.m and can produce finished beads 
in a variety of specific sizes as needed. 
In the instant invention, a bead as shown in FIG. 4 can be made by the 
above process by liquefying a polymer, such as by dissolving it in a 
solvent or melting it, and suspending or dissolving the desired additive 
or additives in the liquid and then feeding the suspension or solution to 
the rotating surface. In the preferred embodiment, bulk 
polymethyl-methacrylate (PMMA) homopolymer or polymethylmethacrylate 
styrene (PMMAS) co-polymer with no or minimal residual BPO, and a 
molecular weight of at least 100,000 is dissolved in an organic solvent 
such as acetone, methylene chloride, or other known organic solvent. BPO, 
typically in the form of a fine powder, is dissolved (or suspended 
depending on the solvent used) in the polymer solution. Since the beads 
are formed directly from a polymer rather than in a polymerization 
reaction, any desirable BPO concentration can be achieved without 
affecting the molecular weight of the polymer. In addition BaSO.sub.4 may 
be suspended in the solution. The suspension is fed to the rotating 
atomization equipment where centrifugal force causes the suspension to 
atomize when it leaves the rotating surface. In the preferred embodiment 
the process is used to form a batch of larger beads containing BaSO.sub.4 
and a batch of smaller beads containing BPO. These are then combined in 
the cement dry component in the desired amounts. 
The pure polymer beads formed from excess coating material can be recycled 
or incorporated as fine beads into the dry component of the cement system 
to provide desired properties. The process can also be run without any 
additives to produce only pure polymer beads for incorporation into the 
dry component. Other additives that can be advantageously placed in beads 
include dyes, antibiotics, bone growth factors, and other pharmacological 
or therapeutic agents. This process is particularly suited to 
incorporating fragile pharmacological agents because of the potential for 
a very short dwell time of the additive in solution and the ability to 
conduct the process at low temperatures. 
A layered bead as shown in FIG. 5 can be produced by iteratively using the 
beads from a prior coating step as the particles in subsequent coating 
steps. For example, a bead having BaSO.sub.4 encapsulated at its center 
surrounded by a concentrated band of BPO and an outer barrier layer of 
pure PMMA can be produced by the following steps. A first bead containing 
BaSO.sub.4 is produced by solidifying a first liquified polymer 
composition containing liquified PMMA and BaSO.sub.4. This first bead is 
then suspended in a solution containing BPO, such as BPO dissolved in 
methanol. (The first bead is not soluble in methanol. However, it is 
possible to use the process of this invention to coat a bead soluble in 
the solution since the dwell time can be made to be so short as to prevent 
dissolution of the bead.) The process is carried out to yield a second 
bead comprising BaSO.sub.4 encapsulated in PMMA, the second bead being 
coated with BPO. The process is repeated with a PMMA solution to apply the 
final PMMA outer layer. 
A wider, less concentrated, BPO containing layer could be produced by 
coating the first beads with a more viscous liquid containing BPO, such as 
liquified PMMA containing BPO, rather than BPO dissolved in methanol. 
A cement system having a dry component comprising these beads in an 
appropriate mix with small beads will have the highly desirable properties 
of a controlled time delay until the onset of polymerization (time to 
dissolve through outer layer of PMMA) followed by rapid polymerization as 
the concentrated layer of BPO becomes available. FIG. 6 depicts the fully 
polymerized cement. The beads 13 will be securely incorporated in the 
polymer matrix 14 since polymerization initiates from the beads. The 
BaSO.sub.4 15 will be securely held in the bead centers where it cannot 
weaken the cement and where it will be uniformly distributed with the 
beads throughout the hardened cement to yield a uniform radiographic 
image. 
Beads according to the present invention having various compositions and 
properties can be produced by repeating the above steps using the beads 
from prior steps with different liquid compositions to form a desired bead 
with stratified additives. 
The present invention provides for careful tailoring of the rheological 
properties of bone cements and for improvement in the strength of bone 
cements. The rheological advantages of the present invention can be best 
understood by referring to FIG. 7 which depicts several exemplary 
viscosity versus time curves obtainable by the inventive cements described 
above. These curves range from immediate, rapid polymerization to delayed 
progressive polymerization. For example, curve 1 represents a cement that 
begins to polymerize immediately and continues to harden very rapidly. 
This type of curve would result from a cement having a high concentration 
of a polymerization initiator in small readily dissolved beads whereby the 
polymerization initiator would all be rapidly released by dissolution of 
the small beads during mixing. Curve 1 would also result from a bead 
having a surface coated with a polymerization initiator. 
Curve 2 represents a cement that begins to polymerize during mixing and 
continues to polymerize at a gradually increasing rate. This curve would 
result from a bead having a polymerization initiator dispersed throughout 
the bead so that some polymerization initiator is exposed immediately and 
as more of the bead dissolves, more polymerization initiator becomes 
available. Curve 2 would also result from a bead having a relatively thick 
outer layer containing polymerization initiator. The polymerization 
initiator would be released gradually, starting immediately during mixing, 
as the outer layer dissolves. 
Curve 3 represents a cement having a delay t.sub.1 before polymerization 
begins and then continued polymerization at a gradually increasing rate. 
This curve would result from a layered bead having an outer layer 
containing no polymerization initiator and a relatively wide inner layer 
containing polymerization initiator so that once the outer layer is 
dissolved, the polymerization initiator begins to be gradually released. 
Such a time delay is advantageous where a longer working time is desirable 
or where the operating environment is excessively warm which would lead to 
accelerated polymerization. 
Curve 4 represents a cement having a relatively long delay t.sub.2 before 
polymerization begins and then rapid polymerization. This curve would 
result from a layered bead structure having a thick outer layer with no 
polymerization initiator and then a very concentrated band of 
polymerization initiator which is released quickly upon dissolution of the 
outer layer. 
Finally, curve 5 represents a cement having a long delay and more gradual 
polymerization. This would result from a layered bead structure having a 
thick outer layer with no polymerization initiator and a wide 
polymerization initiator containing inner layer that would gradually 
release the polymerization initiator. 
While the foregoing has described exemplary embodiments of the present 
invention, further variations are possible. For example, many other 
desirable polymerization curves could be obtained using the techniques of 
this invention. Also, particle sizes may vary depending on the particular 
additive employed and its source. Likewise, the beads may be any 
appropriate shape including but not limited to spheres, discs, flakes, 
rods and irregular or rough spheroids. With regard to the embodiments of 
the present invention containing strata of additives, the additives are 
conveniently located with reference to the center of the bead. For 
example, with spherical or cylindrical beads, the strata are located 
radially outwardly away from the center of the bead. Spherical beads are 
preferred because they result in easier mixing of the cement mixture and 
because they are the natural shape produced by the preferred bead forming 
process of the present invention. Finally, the embodiment of the present 
invention using bead size to control release and retention of additives 
could be combined with the embodiment using layering. An exemplary dry 
component would have larger beads with an opacifier located at the center 
of the beads and smaller beads containing a polymerization initiator that 
would be released by dissolution of the smaller beads. 
With regard to the embodiments of the present invention wherein additives 
are placed in beads of a particular size, the size may be measured in 
terms of diameter, mass, volume or another appropriate measure that will 
yield the selective retention and release of additives of the present 
invention. Preferably, the size is measured in terms of the bead diameter 
or maximum dimension. Also, the smaller beads may be of a different shape 
than the larger beads. For example, the smaller beads may comprise flake 
polymer or milled beads to facilitate dissolution of the smaller beads. 
Likewise, the order, thickness, and concentration of layers in a layered 
bead structure will be varied to suit a particular application and produce 
desired properties. In addition, the cement may comprise a polymer or 
combination of polymers different from those used in the examples. 
However, it will be understood by those skilled in the art that these 
modifications and others may be made without departing from the spirit and 
scope of the invention defined by the appended claims.