CROSS REFERENCE TO RELATED APPLICATIONS
This application is a continuation application of and claims priority under 35 U.S.C. §120 to U.S. patent application Ser. No. 12/708,425, entitled Chemical Mechanical Vapor Deposition Device For Production Of Bone Substitute Material, filed Feb. 18, 2010, which is a continuation application of and claims priority under 35 U.S.C. §120 to U.S. patent application Ser. No. 11/212,977, now U.S. Pat. No. 7,687,098, entitled Chemical Mechanical Vapor Deposition Device for Production of Bone Substitute Material, filed Aug. 26, 2005. Both applications are hereby incorporated by reference in their entirety as though fully set forth herein.
FIELD OF THE INVENTION
This invention relates to production of calcium phosphate mineral-based bone substitute material using a chemical solution spray deposition device that accommodates porous and composite laminar structures with reinforced biocompatible polymer fibers in order to encourage new bone growth as well as to provide mechanical strength and rigidity comparable to natural bone.
BACKGROUND OF THE INVENTION
Bone is an organ composed of hard living tissue providing structural support to the body—it serves as scaffolding. A hard matrix of calcium salts is deposited around protein fibers. Minerals make bone rigid and protein (collagen) provides strength and elasticity. Bone is made of about 70 percent mineral and 30 percent of organic matrix. In an adult, bone engages in a continuous cycle of breaking down and rebuilding. Bone absorbing cells, called osteoclasts, break down bone and discard worn cells. After a few weeks, the osteoclasts disappear, and osteoblasts come to repair the bone. During the cycle, calcium and other minerals are withdrawn from the blood and deposited on the damaged bone surface. The outer layer of bone is called cortical bone; 80 percent of skeletal bone mass is cortical bone. Cancellous bone is an inner spongy structure that resembles honeycomb and accounts for 20 percent of bone mass. The shape of bone is described as long, short, flat, or irregular. The shape is further classified as axial or appendicular. Axial bones are protective. For example, spinal vertebrae protect the spinal cord. Appendicular bones are the limbs. Although there many shapes and sizes of skeletal bone, the bones that make up the spinal column are unique.
Cortical bone is a natural composite which exhibits a rich hierarchical structure. On the microstructural level are the osteons, which are large hollow fibers (about 200 microns in diameter) composed of concentric lamellae and pores. The lamellae are built from fibers, and the fibers contain fibrils. At the ultra-structural level, the fibers are a composite of the mineral hydroxyapatite (HAP) and the protein collagen. These specific structural features are associated with various physical properties. Stiffness of bone arises from the composite structure of mineral crystals and protein fibers. Visco-elastic properties result from slip at bone cement lines between osteon. The cement lines serve as weak interfaces to impart a degree of toughness to bone. As for pores, the lacunae are ellipsoidal pores, which provide space for the osteocytes, the living cells of bone. The pore structure of bone is essential in maintaining its viability and consequently its ability to adapt to mechanical stress. The processes of bone formation (osteogenesis) are involved with osteoinduction and osteoconduction. Osteoconduction is defined as the ability to stimulate the attachment, migration, and distribution of vascular and osteogenic cells within the graft material. Osteoinduction is defined as the ability to stimulate the proliferation and differentiation of pluripotent mesenchymal stem cells. The physical characteristics that affect the graft's osteoconductive activity include porosity, pore size, and three-dimensional architecture. In addition, direct biochemical interactions between matrix protein and cell surface receptors play a major role in the host's response to the graft material. The ability of a graft material to independently produce bone is termed its direct osteogenic potential. To have direct osteogenic activity, the graft preferably contains cellular components that directly induce bone formation.
Natural bone grafts have been extensively used to promote new bone growth (osteogenesis) in the orthopedic industry. Natural bone mineral is fundamentally a mixture of amorphous and crystalline calcium phosphate of HAP (hydroxyapatite) with Ca/P ratio of around 1.6. Natural bone grafts are associated with problems such as limited availability and risky recovery procedure for the autogenous bone, and risks of viral transmission and immune reaction for allograft bone from a cadaver. Consequently, biocompatible matrices are currently being developed to stimulate bone formation via osteoconduction and to promote osteoinduction by using osteogenic growth factors. The biocompatible material should satisfy the following: 1) incorporation and retaining of mesenchymal cells in tissue culture, 2) rapid induction of fibrilvascular invasion from the surrounding tissues, 3) having significant osteoconductive properties with the host bone, 4) no significant immune responses, 5) biomechanical properties similar to normal bone, 6) biodegradable properties with an absorption rate parallel to the rate of new bone deposition, and 7) sites with noncovalently binding osteogenic biomolecules to enhance osteoinduction. Numerous polymeric systems have been studied, including poly-α-hydroxy esters, polydioxanone, propylene fumarate, poly-ethylene glycol, poly-orthoesters, polyanhydrides, etc. These systems have the advantages of being already approved for use in humans and are available with varying porosities in any three-dimensional shape, and have been shown to be an excellent substrate for cellular or bioactive molecule delivery. Other types of materials include HAP (hydroxyapatite) and β-TCP (tricalcium phosphate). They have been the two most intensely studied materials for bone repair and regeneration. Their most unique property is chemical similarity to the mineralization phase of bone. This similarity accounts for their osteoconductive potential and excellent biocompatibility. Both HAP and β-TCP have been shown to be excellent carriers of osteoinduction growth factors and osteogenic cell population. However, by and large, metal, ceramic or polymer materials that have been introduced for bone substitutes have been substantially denser, heavier and significantly stiffer than natural bone although some ceramic materials exhibit similar chemical properties. Natural bone fails gradually when stressed under high compression. By contrast, bone substitute ceramic materials commonly show sudden and catastrophic failure under compression, because most of the bone substitute materials individually lack the several areas of biomechanical properties of natural bone, such as elasticity, viscoelasticity and lamellar structural properties.
What is needed is a calcium phosphate-based bone substitute material, and method of fabrication thereof, that is biocompatible with natural bone, is resorbable for osteogenesis, is rigid, is elastic with reinforced biocompatible polymer fibers, is viscoelasticity through use of multi-layered laminar structures, has controlled porosity, and has pore size(s) comparable to natural bone. The bone substitute should be strong and tough enough to support the spinal column for spinal surgeries as well as many other orthopedic applications.
SUMMARY OF THE INVENTION
These needs are met by the invention, which provides a production device and manufacturing processes, for bone substitute material with excellent osteoconductive and osteoinductive characteristics, that perform chemical solution spray deposition (CSSD) method incorporated with fiber reinforcing, isostatic press. The production device and manufacturing processes presented here rationally simulate natural bone repairing and building processes under various mechanical stresses.
In order to simulate the processes of osteoblasts and osteoclasts in natural bone rebuilding or new bone formation, a chemical solution spray deposition method is presented. In this process, solutions, which include calcium and phosphate ions in separate containers, are mechanically and simultaneously sprayed into an isolated chamber with formation of significant number of small solution particles (500 nanometers to 20 micro meters) in a liquid state. One container contains saturated solution of calcium chloride (CaCl2 (aq)). The other container contains saturated solution of hydrogen phosphate (H3PO4 (aq)). Optionally, a third container can be added to contain saturated solution of hydrogen carbonate (H2CO3 (aq)). And finally, another container with distilled water is added into the system to control a degree of saturation during the chemical reaction, i.e., high and low supersaturated states. It is noted that the proportion of phosphate co-precipitated depends on the temperature, pH and the concentration of calcium co-precipitating chemicals.
where σ is the maximum surface density of phosphorus, A is the surface area of phosphorus molecule, and the function h varies between Ca 0.1 and 0.9. This relation predicts the ratio of calcium to phosphorus for chemical formation of calcium phosphates precipitation, leading to the control of pH, the optimal concentration and the desirable particle sizes of each chemical during the chemical solution spray process.