Nanohydroxyapatite Coatings, Powders and Platelets Produced via Sol-Gel Methods for Medical Applications

Materials having structures and sizes that fall within the range of 1 to 100 nm are referred to as nanostructured materials. Nanostructured materials are associated with a diversity of uses within the medical field, for instance, nanoparticles in drug-delivery systems, in regenerative medicine and in biomaterials science and diagnostic systems.^1,2

The synthesis techniques most commonly used for the manufacture of nanoceramics include pressing, and wet chemical processing techniques such as sol-gel and co-precipitation, all of which have been used to produce nanocoatings, nanoparticles, and nanostructured solid blocks and shapes.

The Sol-Gel Process

Sol-gel processing is unique in that it can be used to manufacture coatings, monoliths, fibers, powders or, platelets of the same composition, simply by varying the viscosity, chemistry, and other factors of a given solution.

By definition, a sol is a suspension of colloidal particles in a liquid. A sol differs from a solution in that a solution is a single-phase system, on the other hand, a sol is a two-phase, solid-liquid system. Gels are regarded as composites, since gels consist of a solid network or skeleton that surrounds a liquid phase or excess solvent. Depending on their chemistry, gels can be soft and have a low elastic modulus, usually obtained through controlled polymerization of the hydrolyzed starting compound. In this case, a three-dimensional network forms, resulting ultimately in a high molecular weight polymeric gel. The resulting gel can be thought of as a macroscopic molecule that extends throughout the solution. This gelation can be used to produce a nanostructured monolith or nanosized coatings, depending on the process applied.^1,2

The advantages of the sol-gel technique are numerous: it results in a stoichiometric, homogeneous and pure product, owing to mixing on the molecular scale; it is of the nanoscale; high purity can be maintained as grinding can be avoided; it allows reduced firing temperatures due to the small particle sizes with high surface areas; it can be used to produce uniform, fine-grained structures; it allows the use of different chemical routes and; it is easily applied to complex shapes with a range of coating techniques. Sol-gel coatings also have the added advantage that the cost of the precursors are relatively unimportant, owing to the small amounts of materials required.^1,2

Thin film deposition using the sol-gel technique also offers the advantage over other deposition techniques such as physical and chemical vapor deposition, in which properties such as surface area and pore volume can be controlled by chemistry.

Nanohydroxyapatite (NanoHap) Powders for Medical Applications

Bone mineral is composed of nanoplatelets which originally were described as hydroxyapatite or HAp, and similar to the mineral dahllite. Today, it is agreed that bone apatite may be better described as carbonate hydroxyapatite, and approximated by the formula (Ca,Mg,Na)₁₀(PO₄CO₃)₆(OH)₂.

The most important parameters for orthopedic implants specifically under articulating conditions are that they have the necessary wear resistance, allow for an adequate attachment to bone, and display the required mechanical properties such as ductility, elasticity and strength. The answer to these pertinent requirements may lie in appropriately designed, macro and micro textured implants that can be coated with nanoscale bone-like calcium phosphates that can induce enhanced bioactivity and provide good adhesion between the implant and the bone.

Nanotechnology has opened up innovative techniques for producing bone-like synthetic nanopowders and hydroxyapatite coatings. Although not called nanopowders, nanoscale materials have existed since the dawn of science using a range of chemical routes. Nanoscale coatings of hydroxyapatite were only introduced in the early 1990's.^2-5 However, without a doubt, the availability of hydroxyapatite sol-gel nanocoating and powder production technology has opened up new opportunities to design superior biocompatible coatings for implants, and the development of high-strength dental and orthopedic nanocomposites for medical applications.¹

Although, bone-like HAp nanopowders and nanoplatelets (Figure 1) can be synthesized by a range of production methods, one very promising approach has been to synthesize these materials via a sol-gel solution.

Figure 1. Nanocrystalline carbonate apatite platelets produced using the Sol-Gel Process.

The results of earlier studies have shown that, while biphasic sol-gel HAp products are easily synthesized, monophasic HAp powders and coatings are more difficult to produce. Although a number of international companies produced nano powders of HAp only one Australian company was successful in producing bone like carbonate HAp nanoparticles, nanoplatelets with diameters in the range of 15 to 20 nm, and with HAp nanocoatings of 70 nm thick. The nanoparticles and nanoplatelets of HAp provide excellent bioactivity for integration into bone, which arises from their very high surface areas.^3,4

Sol-Gel Nanohydroxyapatite and Nanocoated Coralline Apatite

Coralline hydroxyapatite are mainly used as bone graft materials. A number of companies have marketed coralline apatites since 1980's but because of the nature of the conversion process, these coralline bone grafts have retained coral or free CaCO₃, which does not allow the material to be used under load bearing conditions. The structure of commercial coralline HAp also possesses meso- and nano-pores within the inter-pore trabeculae. These nanopores and related large surface areas result in a high dissolution rate. This return results in reduce strength, and early collapse of the structure is observed. These products can not be utilized where high structural strength is required such as the long bones without internal or external fixation devices. To overcome these limitations and improve strength, a new patented double-stage conversion technique was developed by Ben-Nissan and coworkers.^2,4,5,6,7,8

The current technique involves a two-stage application route whereby, in the first stage, a complete conversion of coral to pure HAp is achieved. In the second stage, a sol-gel-derived hydroxyapatite nanocoating is applied directly to cover the meso- and nanopores within the intra-pore material, while maintaining the large pores for appropriate bone growth. The process is shown in Figure 2.

igure 2. Stages of nanocrystalline hydroxyapatite-coated coralline apatite formation. (top) Coral Structure. (middle) Coral after conversion to hydroxyapatite with the hydrothermal method. (bottom) Converted and nanocoated coralline apatite.

The application of a hydroxyapatite sol-gel coating onto the monophasic hydroxyapatite derived from the hydrothermal method improved its mechanical properties. This conversion and nanocoating was reported to increase the compressive strength by 400% over natural coral. Animal trials carried out on tibial components of sheep showed new bone formation and excellent biointegration similar to our natural bone while still retaining structure and strength.

Summary

There has been a major increase in interest in nanostructured materials in advanced technologies during the past decade. The current research and development in the field of nanocoatings are encouraging. Sol-gel derived coatings demonstrate promise owing to their relative ease of production, ability to form a chemically and physically uniform and pure coating over complex geometric shapes. Nanobioceramics are essential to the design and development of a wide range of new medical implants and slow drug delivery devices.

References

1. B. Ben-Nissan and A.H. Choi. Nanoceramics for medical applications. In: Advanced Nanomaterials, (Eds) K. E. Geckeler, H. Nishide ,ISBN: 978-3-527-31794-3 Wiley-VCH, Dec 2009, 523-553.
2. B. Ben-Nissan and A.H. Choi. Sol-gel production of bioactive nanocoatings for medical applications. Part 1: an introduction, Nanomedicine 1(3), 2006, 311-319
3. A.H. Choi and B. Ben-Nissan. Sol-gel production of bioactive nanocoatings for medical applications. Part II: current research and development, Nanomedicine 2(1), 2007, 51-61.
4. C. S Chai and B. Ben-Nissan, Bioactive Nanocrystalline Sol-gel Hydroxyapatite Coatings. J. Mater. Sci: Mater Med. 10: 1999, 465-469.
5. B. Ben-Nissan and C. S Chai, Sol-Gel Derived Bioactive Hydroxyapatite Coatings, In Advances in Materials Science and Implant Orthopaedic Surgery, NATO ASI Series, Series E: Applied Sciences, (Eds.) R. Kossowsky and N.Kossovsky, Kluwer Academic Publishers, ISBN 0-7923- 3558-9, 1995, Vol. 294, 265-275.
6. H. Zreiqat, et. al. The effect of surface chemistry modification of titanium alloy on signaling pathways in human osteoblasts. Biomaterials 26, 2005, 7579-7586.
7. B. Ben-Nissan, "Natural Bioceramics: from coral to bone and beyond", Current Opinion in Solid State and Materials Science, 7, Issues 4-5, 2003, 283-288
8. B. Ben-Nissan., D.Green, G. S. K. Kannangara, C. S Chai. and A. Milev, "31P NMR Studies of Phosphite Derived Nanocrystalline Hydroxyapatite", J. Sol-Gel Sci. and Tech., 21, 2001, 27-37.