Bioactive layers, which induce apatite formation on their surfaces in the living body and bond to living bone through this apatite layer, can be formed on various kinds of metals and polymers by simple chemical and heat treatments. They are easily and uniformly formed even on irregular inner surfaces of porous materials. Their functions can be varied by incorporating different ions into the bioactive layers through the chemical treatments. Metals and organic polymers formed with these novel bioactive layers on their surfaces are used in various applications in the orthopedic and dental fields, such as hip and knee joints, spinal fusion devices, and dental implants, because of their high fracture toughnesses and ductility, properties that are lacking in bioactive ceramics, as well as high bioactivities. Formation of different kinds of bioactive layers on metals and polymers by various methods, and the structure, properties, and clinical applications of the resultant products are reviewed in this chapter.

The authors of this chapter fabricated titanium foams with different structures for bone tissue engineering by the powder sintering method and the selective laser melting method. The advantages and disadvantages of each method as well as the structural characteristics and mechanical properties of the foams fabricated by each method are described based on their experience. These foams were implanted into rabbits or dogs before and after chemical and heat treatments for inducing bioactivity. The foams after the treatments exhibited osteoconduction as well as osteoinduction. These bioactive foams were successfully applied to a lumbar interbody fusion procedure in patients without the need for an autogenic bone graft.

Various kinds of surface modifications of titanium scaffolds have been attempted for the purpose of inducing their bone-bonding ability. Among them, chemical and heat treatments are simple, inexpensive, and easily applied uniformly, even for the inner surface of the pores of medical devices having a complex shape. In this chapter, some simple chemical and heat treatments that are effective for inducing bone-bonding as well as osteoconduction and osteoinduction are described.

The chemical and heat treatments of metallic biomaterials for the purpose of inducing bone-bonding via forming apatite on the material surface in the body are reviewed. It has been reported that Ti metal bonds to living bone through apatite formation on its surface in the body environment upon heat treatment after exposure to strong acid or alkali solutions so as to become positively or negatively charged on its surface. Successful examples of clinical applications of the resultant products are also provided.

Ti15Zr4Nb4Ta and Ti29Nb13Ta4.6Zr, which do not contain the potentially cytotoxic elements V and Al, represent a new generation of alloys with improved corrosion resistance, mechanical properties, and cytocompatibility. Recently it has become possible for the apatite forming ability of these alloys to be ascertained by treatment with alkali, CaCl2, heat, and water (ACaHW). In order to confirm the actual in vivo bioactivity of commercially pure titanium (cp-Ti) and these alloys after subjecting them to ACaHW treatment at different temperatures, the bone bonding strength of implants made from these materials was evaluated. The failure load between implant and bone was measured for treated and untreated plates at 4, 8, 16, and 26weeks after implantation in rabbit tibia. The untreated implants showed almost no bonding, whereas all treated implants showed successful bonding by 4weeks, and the failure load subsequently increased with time. This suggests that a simple and economical ACaHW treatment could successfully be used to impart bone bonding bioactivity to Ti metal and Ti–Zr–Nb–Ta alloys in vivo. In particular, implants heat treated at 700°C exhibited significantly greater bone bonding strength, as well as augmented in vitro apatite formation, in comparison with those treated at 600°C. Thus, with this improved bioactive treatment process these advantageous Ti–Zr–Nb–Ta alloys can serve as useful candidates for orthopedic devices.

Many studies have shown that certain biomaterials with specific porous structures can induce bone formation in non-osseous sites without the need for osteoinductive biomolecules, however, the mechanisms responsible for this phenomenon (intrinsic osteoinduction of biomaterials) remain unclear. In particular, to our knowledge the type of pore structure suitable for osteoinduction has not been reported in detail. In the present study we investigated the effects of interconnective pore size on osteoinductivity and the bone formation processes during osteoinduction. Selective laser melting was employed to fabricate porous Ti implants (diameter 3.3 mm, length 15 mm) with a channel structure comprising four longitudinal square channels, representing pores, of different diagonal widths, 500, 600, 900, and 1200 μm (termed p500, p600, p900, and p1200, respectively). These were then subjected to chemical and heat treatments to induce bioactivity. Significant osteoinduction was observed in p500 and p600, with the highest observed osteoinduction occurring at 5 mm from the end of the implants. A distance of 5 mm probably provides a favorable balance between blood circulation and fluid movement. Thus, the simple architecture of the implants allowed effective investigation of the influence of the interconnective pore size on osteoinduction, as well as the relationship between bone quantity and its location for different pore sizes.

Selective laser melting (SLM) is a useful technique for preparing three-dimensional porous bodies with complicated internal structures directly from titanium (Ti) powders without any intermediate processing steps, with the products being expected to be useful as a bone substitute. In this study the necessary SLM processing conditions to obtain a dense product, such as the laser power, scanning speed, and hatching pattern, were investigated using a Ti powder of less than 45 μm particle size. The results show that a fully dense plate thinner than 1.8 mm was obtained when the laser power to scanning speed ratio was greater than 0.5 and the hatch spacing was less than the laser diameter, with a 30 μm thick powder layer. Porous Ti metals with structures analogous to human cancellous bone were fabricated and the compressive strength measured. The compressive strength was in the range 35-120 MPa when the porosity was in the range 75-55%. Porous Ti metals fabricated by SLM were heat-treated at 1300 °C for 1h in an argon gas atmosphere to smooth the surface. Such prepared specimens were subjected to NaOH, HCl, and heat treatment to provide bioactivity. Field emission scanning electron micrographs showed that fine networks of titanium oxide were formed over the whole surface of the porous body. These treated porous bodies formed bone-like apatite on their surfaces in a simulated body fluid within 3 days. In vivo studies showed that new bone penetrated into the pores and directly bonded to the walls within 12 weeks after implantation into the femur of Japanese white rabbits. The percentage bone affinity indices of the chemical- and heat-treated porous bodies were significantly higher than that of untreated implants.

Glass-ceramics (A-W) containing apatite and wollastonite phases have been developed that show good bio-compatibility and rapidly form chemical bonds with living bone. The glass-ceramic (A-W) was implanted with 200 keV Zr and Ar ions at doses of 1E15 to 1E17 ions/sq.cm. It was found that the Zr ion implantation was effective for obtaining high mechanical strength in simulated body fluid. The increase of the mechanical strength can be considered to be due to the formation of Zr and O bonds by ion implantation. The bioactivity of the implanted ceramics remained, and was improved after soaking in the simulated body fluid. In the case of Ar ion implantation, the fracture strength was not improved. However, the bioactivity was strong and improved with increase of the time soaked in the simulated body fluid.

Porous titanium (Ti) metal with a structure similar to that of human cancellous bone was fabricated by selective laser melting (SLM) process. SEM observation showed that the core part of the walls of the porous body was completely melted by the laser beam and weakly bonded with small Ti particles on its surface. These Ti particles were joined with the core part by heating above 1000 °C, with remaining micro cavities on their surfaces. Tensile strength of the as-prepared solid rod was 530MPa and gradually decreased with increasing temperatures to 400MPa at 1300 °C, whereas its ductility increased with increasing temperatures. NaOH treatment formed fine network structure of sodium hydrogen titanate (SHT) on the walls of the porous Ti metal. The SHT was transformed into hydrogen titanates by HCl treatment and finally anatase and rutile by the heat treatment. Thus treated porous Ti metal formed apatite on its surface in simulated body fluid (SBF) within 3 days.

In the present study, to evaluate the effect of pore size on bone ingrowth, we fabricated lotus stem-type titanium implants each with 4 square holes (diagonal length: 500, 600, 900 and 1200 μm) by using the rapid prototyping process with selective laser melting. These were then subjected to chemical and heat treatments to induce bioactivity. There were significant differences between bone ingrowth on the bioactive-treated and untreated implants. There were no significant differences for bone ingrowth among all holes in both implants. However, in both implants, the 1200-μm was found to be the best for bone invasion in the early stages of growth. On the other hand, both 500and 600-μm were found to be suitable for bone ingrowth from 6 weeks to 26 weeks in treated implants. Thus, the simple architecture of the implants allowed effective investigation of the influence of the interconnective pore size on osteconduction.

Surface structural change of titanium metal with NaOH and heat treatments and the subsequent soaking in a simulated body fluid (SBF) was investigated by observing cross section of its surface layer by scanning electron microscope. A layer of lathlike phase of sodium hydrogen titanate was formed on the surface of the titanium metal 1 µm in thickness by the NaOH treatment. This was transformed into a layer of lathlike form a little densified of sodium titanate and rutile by the subsequent heat treatment. In SBF, apatite started to precipitate in the interior of the surface lathlike layer, filled the interspaces of the lathlike phases and grew over the surface. This integration of the apatite with the surface lathlike layer might be responsible for the strong bonding of the titanium metal to the living bone.

Bioactive chitosan microparticles can be prepared successfully by treating them with a calcium silicate solution and then subsequently soaking them in simulated body fluid (SBF). Such a combination enables the development of bioactive microparticles that can be used for several applications in the medical field, including injectable biomaterial systems and tissue engineering carrier systems. Chitosan microparticles, 0.6μm in average size, were soaked either for 12h in fresh calcium silicate solution (condition I) or for 1h in calcium silicate solution that had been aged for 24h before use (condition II). Afterwards, they were dried in air at 60°C for 24h. The samples were then soaked in SBF for 1, 3 and 7 days. After the condition I calcium silicate treatment and the subsequent soaking in SBF, the microparticles formed a dense apatite layer after only 7 days of immersion, which is believed to be due to the formation of silanol (Si–OH) groups effective for apatite formation. For condition II, the microparticles successfully formed an apatite layer on their surfaces in SBF within only 1 day of immersion.

Simulated body fluid (SBF) and three kinds of bioactive glasses were prepared for bioactivity evaluation tests. These glasses have different bioactiviity due to the different Na2O–CaO–SiO2 chemical composition. The glass surface after being soaked in the SBF was studied by thin film X–ray diffraction spectrometry (TF–XRD) and scanning electron microscope-energy dispersion x-roy spectrometry (SEM–EDS). Soaking time to identify hydroxyapatite precipitated on the surface of the bioglasses in the SBF was measured by TF–XRD. Based on the analysis of bioactivity of the glass and the soaking time, a new index to evaluate ihe bioactivity of materials was proposed.

OBJECTIVES:To research the crystal structure and surface morphology of anodic films on titanium metal in different electrolytes under various electrochemical conditions and investigate the effect of the crystal structure of the oxide films on apatite-forming ability in simulated body fluid (SBF). METHODS:Titanium oxide films were prepared using an anodic oxidation method on the surface of titanium metal in four different electrolytes: sulfuric acid, acetic acid, phosphoric acid and sodium sulfate solutions with different voltages for 1 min at room temperature. RESULTS:Anodic films that consisted of rutile and/or anatase phases with porous structures were formed on titanium metal after anodizing in H(2)SO(4) and Na(2)SO(4) electrolytes, while amorphous titania films were produced after anodizing in CH(3)COOH and H(3)PO(4) electrolytes. Titanium metal with the anatase and/or rutile crystal structure films showed excellent apatite-forming ability and produced a compact apatite layer covering all the surface of titanium after soaking in SBF for 7d, but titanium metal with amorphous titania layers was not able to induce apatite formation. SIGNIFICANCE:The resultant apatite layer formed on titanium metal in SBF could enhance the bonding strength between living tissue and the implant. Anodic oxidation is believed to be an effective method for preparing bioactive titanium metal as an artificial bone substitute even under load-bearing conditions.

All bioactive materials developed up to 1990 were based on calcium phosphate. It was later revealed that materials that form bonelike apatite on their surfaces in the living body bond to living bone through the apatite layer, and that apatite formation on a material is induced by various functional groups on its surface. Based on these findings, bioactive titanium was prepared by forming sodium titanates on its surface via NaOH and heat treatments, and applied to an artificial total hip joint. Porous titanium metal able to exhibit osteoconductivity as well as osteoinductivity was prepared by forming anatase on its surface via NaOH, HCl and heat treatments. Various bioactive materials with different physical properties are expected to be derived from ceramics, metals and organic polymers by modifying their surfaces with functional groups effective for apatite nucleation.

Titania-based materials are easily formed on titanium metal and its alloys by chemical and thermal treatments. Metals can be used under high load conditions, because of their high fracture toughness, but they do not bond to living bone and are usually fixed to the surrounding bone by a mechanical interlocking with the bone via a roughened surface or by filling polymethylmethacrylate bone cement into a gap between a metallic implant and the bone. Fixation using these methods is not stable for long periods, and sometimes autogenous bone is transplanted around metallic implants for fixation. However, harvesting of the autogenous bone involves excessive invasion and sometimes leads to complications. In view of these facts, it would be desirable for metallic implants to exhibit bone-bonding capability. To provide a bone-bonding capability to a metallic material, a coating of calcium phosphate on a metallic implant using a plasma-spray technique has been developed and used clinically. However, in this method, calcium phosphate is only coated on the surfaces exposed to the plasma and the coated layer is relatively thick; hence, a uniform bioactive layer cannot be formed on complex shapes. In contrast to this, thin, uniform titania-based coatings can be formed on all surfaces, even on complex shapes using solution and thermal treatments of the metal. This chapter describes the formation of titania-based materials on metals, the properties of these titania-based materials, and the mechanism of apatite formation on these titania-based materials.

Bioactive materials are clinically used as important bone substitutes. However, even these bioactive materials cannot replace all auto grafts. Bioactive materials with higher bone-bonding ability and different mechanical properties need to be developed. Most of the bioactive materials hitherto developed form an apatite layer on their surfaces in the living body and then bond to bone through this apatite layer. This in vivo apatite formation can be reproduced on the surfaces of materials in Simulated Body Fluid (SBF) with ion concentrations nearly equal to those of human blood plasma. SBF is used by many researchers for in vitro evaluation of the bone bioactivity of materials and SBF has been standardized as a solution for in vitro evaluation of apatite-forming ability of implant materials by the International Organization for Standardization. This chapter describes the ion concentrations of SBF, the correlation of the bone-bonding ability of materials with apatite formation on their surfaces in SBF, some applications of in vitro evaluation of bone-bonding ability, and the mechanisms of apatite formation.

We have developed a porous titanium implant sintered with spacer particles (porosity = 50 %, average pore size ± standard deviation = 303 ± 152 !m, yield compression strength = 100MPa). This porous titanium was successfully treated with chemical and thermal treatment that gives a bioactive micro-porous titania layer on the titanium surface, and it is expected as effective biomaterial for biological fixation on load bearing condition. In this study, ten adult female beagle dogs underwent anterior lumbar interbody fusion at L6-7 using either BT-implant or non-treated implant (NT-implant), then followed by posterior interspinous wiring and facet screw fixation. The radiographic evaluations were performed 1, 2 and 3 months postoperatively using X-ray fluoroscopy. Animals were sacrificed after 3 months postoperatively, and fusion status was evaluated by manual palpation. Histological evaluation was also performed. Both histological and radiological evaluation revealed that interbody fusion was achieved in 5 of 5 dogs (100%) in BT-group and 3 of 5 dogs (60%) in NT-group. In BT implants, we could observe a large amount of new bone formation from periphery to the center of the implant, whereas in NT implants, fibrous tissue formation was still observed even in the implants with successful fusion. The results of this study indicate that porous bioactive titanium implant will represent a new osteoconductive biomaterial with improved fusion characteristics.

Bioactive materials hitherto clinically used are based on silicate or phosphate. Recently, various kinds of bioactive materials with different mechanical properties are being developed on the basis of titania. A bioactive material with high fracture toughness was obtained by surface modification of titanium metal with an amorphous sodium titanate. An osteoinductive material with high mechanical strength was obtained by surface modification of porous titanium metal with anatase. A bioactive material with high flexibility was obtained by surface modification of polyethylene terephthalate fiber fabric with brookite. A bioactive material with analogous mechanical properties to those of human cortical bone was obtained by dispersing nano-sized anatase particles in a polyethylene. A bioactive material with self-setting property was obtained by mixing anatase particles with polymethyl methacrylate (PMMA) particles of a conventional PMMA cement.

Covalent coupling of sulfonic group (–SO 3 H) was attempted on different polymers to evaluate efficacy of this functional group in inducing nucleation of apatite in body environment, and thereupon to design a simple biomimetic process for preparing bonelike apatite-polymer composites. Substrates of polyethylene terephthalate (PET), polycaprolactam (Nylon 6), high molecular weight polyethylene (HMWPE) and ethylene-vinyl alcohol co-polymer (EVOH) were subjected to sulfonation by being soaked in sulfuric acid (H 2 SO 4 ) or chlorosulfonic acid (ClSO 3 H) with different concentrations. In order to incorporate calcium ions, the sulfonated substrates were soaked in saturated solution of calcium hydroxide (Ca(OH) 2 ). The treated substrates were soaked in a simulated body fluid (SBF). Fourier transformed infrared spectroscopy, thin-film X-ray diffraction, and scanning electron microscopy showed that the sulfonation and subsequent Ca(OH) 2 treatments allowed formation of –SO 3 H groups binding Ca 2+ ions on the surface of HMWPE and EVOH, but not on PET and Nylon 6. The HMWPE and EVOH could thus form bonelike apatite layer on their surfaces in SBF within 7 d. These results indicate that the –SO 3 H groups are effective for inducing apatite nucleation, and thereby that surface sulfonation of polymers are effective pre-treatment method for preparing biomimetic apatite on their surfaces.