Composite macrostructure of ceramic and organic biomaterials

A composite self-supporting flexible agglomerated macrostructure is described which comprises (1) a matrix of unfibrillated polytetrafluoroethylene resin and addition curable silicone and (2) particulate material including hydroxyapatite and/or tricalcium phosphate uniformly distributed throughout said matrix, the macrostructure being uniformly permeated by a network of open pores formed in the process of manufacture by intimately blending particulate sodium chloride and subsequently leaching the sodium chloride particles.

This invention relates to the field of biomaterials, more particularly to 
the field of bioceramic materials and most particularly to the field of 
composites of ceramic and organic biomaterials. 
A biomaterial is a substance designed for implantation within or 
incorporation with a living system, which includes for example anything 
that is intermittently or continuously exposed to body fluids although 
they may actually be located outside of the body proper. 
Biomaterials in the form of surgical implants have been manufactured from 
metals, plastic, rubber, textiles, ceramics and certain composites 
thereof. Since bioceramic materials can exist in either inert, 
surface-active or resorbable forms, the uses of such materials are 
manifold, such as for example artificial heart valves, knee and hip joint 
prostheses, alveolar ridge reconstructions, tooth/root implants, 
percutaneous access devices, bone plates and artificial tendons. Inert 
bioceramic materials are used for heart valves and electronic implants, 
for example, where durability, impermeability and lack of physiological 
response are needed. The term "inert" refers to materials that are 
essentially stable with little or no tissue reactivity when implanted 
within the living organism. Surface-active bioceramic materials possess 
chemical reactivity with the physiological environment. As healing of the 
incision or wound site occurs, a simultaneous chemical bond between the 
tissue and the implant surface is stimulated. For example, bone will bond 
to dense hydroxyapatite (HA). Resorbable bioceramic materials are 
temporary space fillers or scaffolds for new tissue to develop. Natural 
tissue reconstruction occurs simultaneously with resorption. For example, 
tricalcium phosphate (TCP), having the formula Ca.sub.3 (PO.sub.4).sub.2 
is biocompatible, has the ability to promote the ingrowth of soft tissue 
and bone, especially in the porous state, and is bioresorbable. 
Sintered polytetrafluoroethylene (PTFE) has been used as a biomaterial in 
various forms, such as sutures and solid implants. PTFE biomaterials are 
desirable because of their low density, minimal time-dependent degradation 
characteristics, minimal deterioration in vivo, ease of shaping, 
pliability and ability to be dry sterilized. There are no antibody or 
thrombogenic reactions around PTFE implant sites. 
Medical-grade silicone rubber is a known biomaterial which when vulcanized 
is resilient, easily fabricated, physiologically inert, capable of being 
dry sterilized and has low modulii of elasticity. 
Biomaterials are disclosed in U.S. Pat. Nos. 3,992,725 and 4,129,470, which 
are porous reinforced structures comprising stainless steel, vitreous 
carbon, alumina, zirconia, or other ceramic fibers bonded together by 
"sintered" polytetrafluoroethylene. The exposed surfaces of this material 
are said to have sufficiently high surface tension to be highly blood 
wettable and therefore suitable for ingrowth of tissues. 
It is an object of this invention to provide a composite of disparate 
biomaterials that is self-supporting without the necessity of fibrous or 
fibrillated reinforcement. 
It is a further object of this invention to provide a composite of organic 
and inorganic biomaterials wherein the organic biomaterial constitutes a 
matrix throughout which the inorganic biomaterial is uniformly 
distributed. 
It is a further object of this invention to provide a composite of 
disparate biomaterials that is self-supporting without the necessity of 
fibrous of fibrillated reinforcement and which contains open pores. 
I have now discovered a self-supporting, porous flexible composite of known 
organic and inorganic biomaterials that does not depend upon fibrous or 
fibrillated materials for reinforcement. The present self-supporting 
composite can be readily shaped by molding, carving or abrading into sized 
products which embody the corresponding properties of the component 
biomaterials. 
The composite composition of this invention is a self-supporting flexible 
agglomerated macrostructure comprising (1) a matrix consisting essentially 
of a blend of sintered unfibrillated polytetrafluoroethylene resin and an 
addition cured silicone, said blend having been heated sufficiently to 
sinter the polytetrafluoroethylene and to cure said silicone composition; 
and (2) a particulate material selected from the class consisting of 
hydroxyapatite and tricalcium phosphate, said particulate material having 
a maximum size of about 2,000 microns, and being uniformly distributed 
throughout said matrix; said macrostructure being uniformly permeated by a 
network of open pores. 
The process of manufacturing the composite material of this invention 
comprises the steps of (1) intimately blending a mixture of a major amount 
of unsintered and unfibrillated particulate polytetrafluoroethylene resin 
and minor amounts of (A) a hydrocarbon liquid and (B) an addition curable 
silicone composition containing a crosslinking catalyst, (2) intimately 
blending with the product of step (1) a particulate ceramic material 
selected from the class consisting of apatite and tricalcium phosphate and 
particulate sodium chloride, (3) introducing portions of the product of 
step (2) into opposing streams of air within a mill so as to form a 
homogeneous particulate mixture, (4) subjecting the product of step (3) to 
mechanical pressure, (5) while maintaining pressure subjecting the product 
of step (4) to a temperature sufficient to sinter polytetrafluoroethylene 
and to cure said silicone composition, and (6) solubilizing the 
particulate sodium chloride so as to create a network of open pores in the 
product of step (5) corresponding in size to the original sodium chloride 
particles. The particulate sodium chloride particles may have a maximum 
particle size of about 2,000 microns.

DESCRIPTION OF THE PREFERRED EMBODIMENTS 
Example 1 
29.44 grams (9.11 cc) of apatite (calcium phosphate-tribasic basic--Fisher 
Scientific Company) powder was fired at 12000.degree. C. for 4 hours, then 
ground and sifted to a particle size distribution of: 
25% between 180 and 250 microns 
25% between 90 and 180 microns 
25% between 53 and 90 microns 
25% below 53 microns 
1.51 grams (0.479 cc) of tricalcium phosphate was synthesized by the 
following series of reactions: (confirmed by X-ray diffraction analysis) 
##STR1## 
51.92 grams (23.98 cc) of sodium chloride (biological grade--Fisher 
Scientific Company) was ground and sifted to a particle size distribution 
of: 
25% between [180 and 250 microns 
50% between 90 and 180 microns 
25% between 53 and 90 microns 
3.28 grams (2.88 cc) of Silastic.RTM. MDX4-4210 addition curable silicone 
elastomer (Dow Corning Corporation) was mixed into 3.64 grams (4.60 cc) of 
kerosene (Fisher Scientific Company) using a high sheer blender. The 
silicone ingredients comprised a 10/1 ratio of base to catalyst. The 
resultant solution was then slowly added to 25.30 grams (11.5 cc) of 
molding grade Teflon.RTM. 7A polytetrafluoroethylene (E. I. dupont de 
Nemours and Company, Inc.) and jar tumbled for 8 hours. The apatite, 
tricalcium phosphate and sodium chloride particulates were then added and 
the mixture tumbled for an additional 4 hours. The resultant blend of 
inorganic and organic materials was then introduced into an operating 
Trost Air Mill at 40 psi air pressure. This mill utilizes opposing jets of 
air to cause the material to impact against itself. At this air pressure, 
little or no size reduction of the particulate matter occurs. Within a 
period of two hours (to prevent curing of the silicone resin), the 
air-milled mixture was pressed between plates in a cylindrical die about 
two inches deep and 2.5 inches in diameter at room temperature to about 
5,000 psi pressure. This pressed form was then hot pressed at 340.degree. 
C. and 2,000 psi to "sinter" the polytetrafluoroethylene and cure 
(vulcanize) the silicone elastomer. After cooling, the hot pressed 
material was submerged in a reservoir of distilled water to dissolve the 
sodium chloride component particulates, thereby creating a network of open 
pores with a size distribution corresponding to that of the original salt 
crystals. The leaching treatment was performed over a period of 48 hours 
while maintaining a water solution rich in Ca.sup.++ and PO.sub.4.sup.- 
ions in order to inhibit dissolution of the tricalcium phosphate 
component. Finally, the leached composite material was dried at a 
temperature below 100.degree. C. 
The product produced by the procedure of Example 1 was in the form of a 
cylindrical disc with smooth exterior surfaces. The 2.5 inch disc is 
pliable and resilient in the hands. Extreme tearing force applied by hand 
causes jagged disruption of the composite with the exposed broken internal 
edges having a homogeneous appearance. 
The proportions of the starting materials utilized in Example 1 were chosen 
to effect a final composition of 60 volume percent organic materials and 
40 volume percent ceramic materials, with an overall porosity of 50 volume 
percent. The open pores may have a maximum dimension of about 2,000 
microns. The ceramic phase is 5 volume percent tricalcium phosphate and 95 
volume percent apatite. The organic phase is 20 volume percent silicone 
rubber and 80 volume percent polytetrafluoroethylene. 
Polytetrafluoroethylene (PTFE) in its virgin resin state is on the order of 
95 percent crystalline, unless it has been "sintered". The word "sintered" 
is used in this application to describe the action of heating PTFE above 
its crystalline melting point and then cooling it. Because of its 
extremely high melt viscosity, the molten PTFE retains some of its 
amorphous structure when quenched. This creates a condition known as 
"amorphous locking" which promotes dimensional and chemical stability. 
This invention however does not involve the well-known processes of solid 
state sintering or vitreous sintering. Therefore, the bioceramic materials 
utilized in accordance with the composite of this invention remain 
particulate within the organic matrix formed by the "sintered" PTFE and 
the cured (vulcanized) silicone elastomer.