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Biomedical subjects

Hae-Won Kim

Publications and source records attributed to Hae-Won Kim.

At least 37 records · Page 2Linked to original sources

Hydroxyapatite porous scaffold engineered with biological polymer hybrid coating for antibiotic Vancomycin release.

The purpose of this study is to improve hydroxyapatite (HA) porous scaffolds via coating with biological polymer-HA hybrids for use as wound healing and tissue regeneration. Highly porous HA scaffolds, fabricated by a polyurethane foam reticulate method, were coated with hybrid coating solution, consisting of poly(epsilon-caprolactone) (PCL), HA powders, and the antibiotic Vancomycin. The PCL to HA ratio was fixed at 1.5 and the drug amounts were varied [drug/(PCL + HA) = 0.02 and 0.04]. For the purpose of comparison, bare HA scaffold without the hybrid coating layer was also loaded with Vancomycin via an immersion-adsorption method. The hybrid coating structure and morphology were observed with Fourier transformed infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM). The effects of the hybrid coating on the compressive mechanical properties and the in vitro drug release of the scaffolds were investigated in comparison with bare HA scaffold. The PCL-HA hybrid coating altered the scaffold pore structure slightly, resulting in thicker stems and reduced porosity. With the hybrid coating, the HA scaffold responded to an applied compressive stress more effectively without showing a brittle failure. This was attributed to the shielding and covering of the framework surface by the coating layer. The encapsulated drugs within the coated scaffold was released in a highly sustained manner as compared to the rapid release of drugs directly adsorbed on the pure HA scaffold. These findings suggest that the coated HA scaffolds expand their applicability in hard tissue regeneration and wound healing substitutes delivering bioactive molecules.

Anti-Bacterial Agents↗

Improvement in biocompatibility of ZrO2-Al2O3 nano-composite by addition of HA.

The biocompatibility of zirconia-alumina (ZA) nano-composites in load-bearing applications such as dental/orthopedic implants was significantly enhanced by the addition of bioactive HA. The ZA matrix was composed of nano-composite powder obtained from the Pechini process and had higher flexural strength than conventionally mixed zirconia-alumina composite. Because the ZA nano-composite powder effectively decreased the contact area between HA and zirconia for their reaction during the sintering process, the HA-added ZA nano-composites contained biphasic calcium phosphates (BCP) of HA/TCP and had higher flexural strength than conventionally mixed ZA-HA composite. From the in vitro test with osteoblastic cell-lines, the proliferation and the differentiation (as expressed by the alkaline phosphatase activity) of the cellular response on the HA-added ZA nano-composites gradually increased as the amount of HA added increased. From the mechanical and biological evaluations of the HA-added ZA nano-composites, 30HA (30 vol% HA + 70 vol% ZA) was found to be the optimal composition for load-bearing biological applications.

Alkaline Phosphatase↗

Stability and cellular responses to fluorapatite-collagen composites.

Fluorapatite (FA)-collagen composites were synthesized via a biomimetic coprecipitation method in order to improve the structural stability and cellular responses. Different amounts of ammonium fluoride (NH4F), acting as a fluorine source for FA, were added to the precipitation of the composites. The precipitated composites were freeze-dried and isostatically pressed in a dense body. The added fluorine was incorporated nearly fully into the apatite structure (fluoridation), and a near stoichiometric FA-collagen composite was obtained with complete fluoridation. The freeze-dried composites had a typical biomimetic network, consisting of collagen fibers and precipitates of nano-sized apatite crystals. The human osteoblast-like cells on the FA-collagen composites exhibited significantly higher proliferation and differentiation (according to alkaline phosphatase activity) than those on the hydroxyapatite-collagen composite. These enhanced osteoblastic cell responses were attributed to the fluorine release and the reduced dissolution rate.

Alkaline Phosphatase↗

Fluoridated apatite coatings on titanium obtained by electron-beam deposition.

In this report, a series of fluoridated apatite coatings were obtained by the electron-beam deposition method. The fluoridation of the apatite was aimed to improve the stability of the coating and elicit the fluorine effect, which is useful in the dental restoration area. Apatites fluoridated at different levels were used as initial evaporants for the coatings. The as-deposited coatings were amorphous, but after heat treatment at 500 degrees C for 1 h, the coatings crystallized well to an apatite phase without forming any cracks. The adhesion strengths of the as-deposited coatings were about 40 MPa. After heat treatment at 500 degrees C, the strengths of the pure HA and FA coatings decreased to about 20 MPa, however, the partially fluoridated coatings maintained their initial strength. The dissolution rate of the fluoridated coatings was lower than that of the pure HA coating, and the rate was the lowest in the coatings with 25% and 50% fluorine substitutions. The osteoblast-like cells responded to the coatings in a similar manner to the dissolution behavior. The cells on the fluoridated coatings showed a lower (p < 0.05) proliferation level compared to those on the pure HA coating. The alkaline phosphatase activity of the cells was slightly lower than that on the pure HA coating, but this difference was not statistically significant.

Absorbable Implants↗

Effect of fluoridation of hydroxyapatite in hydroxyapatite-polycaprolactone composites on osteoblast activity.

Fluorine was administered to a system of hydroxyapatite (HA)/polycaprolactone (PCL) ceramic-polymer bioactive composites for applications as hard tissue regeneratives. The HA was fluoridated at different levels (5%, 25%, 50% and 75%) in order to produce the fluor-hydroxyapatite (FHA)/PCL composites. The osteoblastic cellular responses to the composites were examined in terms of the cell attachment, proliferation and differentiation as well as the expression of bone-associated genes. The amount of fluorine released from the composites was controlled by changing the degree of fluoridation, and the cellular responses were strongly influenced by the level of fluoridation. The MG63 cells on the FHA-PCL attached and proliferated at a similar level to those on HA-PCL. However, the fluoridation of HA increased significantly the alkaline phosphatase (ALP) activity and osteocalcin (OC) production by the cells on the composites, which was measured by an enzymatic assay. Moreover, the gene expression level of ALP and OC in the cells was up regulated on the FHA-PCL, which was confirmed semi-quantitatively by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. These findings on the fluorine-administered biological composites (FHA-PCL) suggested that fluorine plays a significant role in stimulating the bone derived cellular activity, and the FHA-PCL composites have high potential for use as hard tissue regeneratives.

Body Fluids↗

Stimulation of osteoblast responses to biomimetic nanocomposites of gelatin-hydroxyapatite for tissue engineering scaffolds.

Collagen-derived gelatin/hydroxyapatite (HA) nanocomposites were biomimetically synthesized for hard tissue engineering scaffold. In vitro osteoblastic cellular responses to the nanocomposites were assessed in comparison with those conventionally mixed gelatin-HA composites. A three-dimensional culture method involving floating cells in a culture medium was introduced to assist in the initial attachment of the cells to the scaffolds, and the proliferation and differentiation behaviors of the cells were examined. The osteoblastic MG63 cells attached to the nanocomposites to a significantly higher degree and subsequently proliferated more. The alkaline phosphatase (ALP) activity and osteocalcin produced by the cells were significantly higher on the nanocomposite scaffolds than on the conventional composite scaffolds. These improved cellular responses on the nanocomposites are considered to result from the increased ionic release and serum protein adsorption on the nanocomposites, which was derived from the different structural and morphological characteristics, i.e., the nanocomposite scaffolds retained less-crystallized and smaller-sized apatite crystals and a more well-developed pore configuration than the conventional ones. Based on these findings, the biomimetically synthesized nanocomposite scaffolds are believed to be potentially useful in hard tissue regeneration and tissue engineering fields.

Alkaline Phosphatase↗

Hydroxyapatite and fluor-hydroxyapatite layered film on titanium processed by a sol-gel route for hard-tissue implants.

A double-layered coating, consisting of a hydroxyapatite (HA) outer film and a fluor-hydroxyapatite (FHA) inner film, was produced on a Ti substrate by a sol-gel route to improve the biocompatibility and functionality of the system. Dissolution behavior of and in vitro cellular responses to the layered film were investigated. Calcium nitrate and triethyl phosphite were used for calcium and phosphate precursors, respectively, and ammonium fluoride was added as a fluorine-ion source for FHA. The FHA layer was deposited on Ti by spin coating and subsequent heat treatment at 550 degrees C for 30 min in air, and then the HA layer was laid down over the FHA-coated Ti under the same conditions. After heat treatment, characteristic apatite structures and phases were developed on both FHA and HA films. The cross-section view of the HA/FHA film clearly showed a double-layered structure on Ti with each layer approximately 0.6-0.8-microm thickness. The coating layer was highly uniform and dense, and adhered to Ti substrate strongly with an adhesion strength of about 40 MPa. The in vitro solubility of the HA/FHA layered film in a physiological solution was between that of HA and FHA pure film, and the dissolution profile was quite biphasic, that is, an initial rapid period and a slowdown with increasing time, reflecting the gradient solubility of the fast HA outer structure/slow FHA inner structure. The human osteoblast-like HOS TE85 cells cultured on the HA/FHA layered film attached, spread, and grew favorably. The proliferation rate of the cells on the layered film was significantly higher (considered at p < 0.05 for n = 6) than that on Ti substrate and was similar to that on pure HA film. The alkaline phosphatase (ALP) activity and osteocalcin (OC) produced by the cells on the layered film were significantly higher (considered at p < 0.05 for n = 6) than those on Ti substrate. Moreover, the ALP and OC levels of cells on the layered film showed the trends of HA outer/FHA inner structure with respect to culture period, that is, HA initially and FHA later. These observations suggest that the HA/FHA layered film on Ti obtained by a sol-gel route possesses gradient functionality in terms of solubility and cellular responses, and find that those parameters can be tailored for specific use in hard-tissue implants.

Biocompatible Materials↗

Effect of biphasic calcium phosphates on drug release and biological and mechanical properties of poly(epsilon-caprolactone) composite membranes.

Poly(epsilon-caprolactone) (PCL) and biphasic calcium phosphate (CaP) composite membranes were prepared for use in tissue regeneration by a novel solvent casting-pressing method. An antibiotic drug, tetracycline hydrochloride (TCH), was entrapped within the membranes to investigate the efficacy of the material as a drug delivery system. The CaP powders were varied in amount (0-50 wt %) and in powder characteristics by heat treating at different temperatures, and their effects on the mechanical and biological properties and drug release of the membranes were examined. With CaP addition up to 30 wt %, the elastic modulus of the membranes was enhanced much due to the rigidity of CaP. While the tensile strength and elongation rate decreased gradually with CaP addition because the CaP powders acted as a failure source. The osteoblast-like cells cultured on the CaP-PCL composite membranes exhibited significant improvements in proliferation and alkaline phosphatase (ALP) activity compared to pure PCL and culture plastic control, indicating excellent cell viability and functional activity. The TCH drugs were released from the PCL and CaP-PCL membranes in a similar fashion; an initial burst followed by a reduced release rate. The initial burst effect diminished much by the addition of CaP powders. The CaP addition increased the drug release rate after an initial period, and this was attributed to the high water uptake capacity and dissolution of the CaP containing membranes. Compared to the composite membranes containing heat-treated CaP powders, those with as-precipitated ones had higher dissolution and drug releases. These observations on mechanical properties and cellular responses as well as on drug release profiles suggested that the CaP-PCL composite membranes are potentially applicable to tissue regeneration and drug delivery system.

Animals↗

Hard-tissue-engineered zirconia porous scaffolds with hydroxyapatite sol-gel and slurry coatings.

A zirconia (ZrO(2)) porous scaffold was coated with a gradient apatite layer to induce osteoconductivity with the use of a combination of sol-gel and powder slurry methods. The ZrO(2) was used to impart mechanical strength and the apatite layer was coated for functional biocompatibility. The coating layer, from the outside in, was composed of sol-gel hydroxyapatite (HA)/slurry HA/slurry FA. The sol-gel coating powder had a lower crystallinity than the slurry coating powder. The sol-gel HA coating over the HA/FA slurry coating layer made the surface very smooth. The sol-gel coating over the slurry coating layer enhanced the bonding strength up to 33 MPa. The dissolution rate of the sol-gel/slurry coating layer was much higher than that of the slurry coating. Moreover, the rate could be controlled by altering the heat-treatment temperature of the sol-gel HA layer. The MG63 cells cultured on these materials grew and spread in a different manner, depending on the coating layer. However, the proliferation rates of the cells on both coating systems were not much different.

Biocompatible Materials↗

Development of hydroxyapatite bone scaffold for controlled drug release via poly(epsilon-caprolactone) and hydroxyapatite hybrid coatings.

A scaffold-coating design, the hydroxyapatite (HA) porous bone scaffold coated with poly(epsilon-)caprolactone (PCL) and HA powder hybrids, was developed for use as tissue-regeneration and controlled-release system. An antibiotic drug, tetracycline hydrochloride (TCH), was encapsulated within the hybrid coating layer through a dip-coating and solvent-casting method. Coating cycle and drug loading amount differed to control the level of drug-release rate. The HA scaffold framework, obtained by a polymeric foam reticulate method, exhibited a highly porous structure, with porosity and pore size of approximately 87% and 180 microm, respectively. The hybrid layer, consisting of PCL sheet and HA fine powders, was uniformly coated on the scaffold surface. The coating layer exhibited only PCL and HA phases and structures, revealing no chemical interaction among the coating components, as observed by X-ray diffraction (XRD) and Fourier-transform infrared (FTIR) analyses. The coated-HA scaffolds showed an effective stress distribution behavior in response to an applied load, as confirmed by the compressive stress-strain curve. The mechanical properties of the coated scaffolds were improved highly with coatings; the compressive strength and elastic modulus of the cyclic coated scaffolds were approximately 3-4 times, and the energy absorption were approximately 8 times, higher than those without coating. These improvements were attributed mainly to the shielding of framework flaws by a flexible coating layer and partially to the thicker stems (porosity reduction). The dissolution of the coated scaffolds in a phosphate-buffered saline (PBS) solution increased with incubation time. The drug was released sharply within the initial several hours ( approximately 2 h), but the rate decreased further, showing a sustained release. The release amount was well controlled via coating-cycle and initial drug loading amount, suggesting the effectiveness of the coating-scaffold design as a drug-delivery system.

Bone and Bones↗

Dissolution control and cellular responses of calcium phosphate coatings on zirconia porous scaffold.

Different types of calcium phosphates [hydroxyapatite (HA), fluorapatite (FA), tricalcium phosphate (TCP), and their composites (HA + FA, HA + TCP)] were coated on a zirconia (ZrO(2)) porous scaffold using a powder slurry method. The ZrO(2) porous scaffold was intended for a load-bearing implant, and the apatite layers were coated to improve osteoconductivity. The insertion of an FA intermediate layer between the coating layer and ZrO(2) scaffold effectively suppressed the reaction between the calcium phosphate and ZrO(2) and maintained the coating layer at the initial powder composition. The obtained coating layer, of a thickness of approximately 30 microm, was relatively microporous and firmly adherent to the ZrO(2) scaffold. Dissolution tests in physiological solution showed typical differences depending on the coating layers, with the dissolution rate increasing in the order TCP > HA + TCP > HA > HA + FA > FA. This result suggests the functional coating of the calcium phosphates in view of tailoring the solubility. Osteoblast-like cells, MG63 and HOS, responded similarly in terms of cell growth, morphology, and proliferation rate regardless of the coating types, indicating favorable and comparable cell viability. However, the alkaline phosphatase (ALP) activity of the cells on the pure HA and HA composite coatings (HA + FA and HA + TCP) expressed at higher levels compared to those on pure FA and pure TCP coatings for both MG63 and HOS cells, suggesting a selective cell activity depending on the coating types. All the calcium phosphate-coated-ZrO(2) scaffolds showed higher ALP levels compared to pure ZrO(2) scaffold.

Biodegradation, Environmental↗

Hydroxyapatite coating on titanium substrate with titania buffer layer processed by sol-gel method.

Hydroxyapatite (HA) was coated onto a titanium (Ti) substrate with the insertion of a titania (TiO2) buffer layer by the sol-gel method. The HA layer was employed to enhance the bioactivity and osteoconductivity of the Ti substrate, and the TiO2 buffer layer was inserted to improve the bonding strength between the HA layer and Ti substrate, as well as to prevent the corrosion of the Ti substrate. The HA layer coated over the TiO2 showed a typical apatite phase at 400 degrees C and the phase intensity increased above 450 degrees C. The sol-gel derived HA and TiO2 films, with thicknesses of approximately 800 and 200 nm, respectively, adhered tightly to each other and to the Ti substrate. The bonding strength of the HA/TiO2 double layer coating on Ti was markedly improved when compared to that of the HA single coating on Ti. The highest strength of the double layer coating was 55 MPa after heat treatment at 500 degrees C. The improvement in bonding strength with the insertion of TiO2 was attributed to the resulting enhanced chemical affinity of TiO2 toward the HA layer, as well as toward the Ti substrate. Human osteoblast-like cells, cultured on the HA/TiO2 coating surface, proliferated in a similar manner to those on the TiO2 single coating and on the pure Ti surfaces. However, the alkaline phosphatase activity of the cells on the HA/TiO2 double layer was expressed to a higher degree than that on the TiO2 single coating and pure Ti surfaces. The corrosion resistance of Ti was improved by the presence of the TiO2 coating, as confirmed by a potentiodynamic polarization test.

Buffers↗

Improved biological performance of Ti implants due to surface modification by micro-arc oxidation.

The surface of a titanium (Ti) implant was modified by micro-arc oxidation (MAO) treatment. A porous layer was formed on the Ti surface after the oxidation treatment. The phase and morphology of the oxide layer were dependent on the voltage applied during the oxidation treatment. With increasing voltage, the roughness and thickness of the film increased and the TiO(2) phase changed from anatase to rutile. During the MAO treatment, Ca and P ions were incorporated into the oxide layer. The in vitro cell responses of the specimen were also dependant on the oxidation conditions. With increasing voltage, the ALP activity increased, while the cell proliferation rate decreased. Preliminary in vivo tests of the MAO-treated specimens on rabbits showed a considerable improvement in their osseointegration capability as compared to the pure titanium implant.

Animals↗

Sol-gel derived fluor-hydroxyapatite biocoatings on zirconia substrate.

Fluor-hydroxyapatite (FHA) film was coated on a zirconia (ZrO(2)) substrate by a sol-gel method. An appropriate amount of F ions was incorporated into the hydroxyapatite (HA) during the preparation of the sols. The apatite phase began to crystallize after heat treatment at 400 degrees C, and increased in intensity above 500 degrees C. No decomposition was detected by X-ray diffraction analyses up to 800 degrees C, which illustrates the high thermal stability of the FHA films. The films showed a uniform and dense morphology with a thickness of approximately 1 microm after a precisely controlled heat treatment process. These FHA films adhered firmly to the zirconia substrate, representing notable adhesion strengths of approximately 70 MPa after heat treatment above 500 degrees C. The dissolution rate of the FHA coating layer varied according to the heat treatment temperature, which was closely related to the film crystallinity. The dissolution rate of the FHA film was lower than that of the HA film, suggesting the possibility of a functional gradient coating of HA and FHA. The MG63 cells seeded onto the FHA films proliferated in a similar manner to those seeded onto pure HA ceramic and a plastic control.

Adhesiveness↗

Fluor-hydroxyapatite sol-gel coating on titanium substrate for hard tissue implants.

Hydroxyapatite (HA) and fluor-hydroxyapatite (FHA) films were deposited on a titanium substrate using a sol-gel technique. Different concentrations of F- were incorporated into the apatite structure during the sol preparation. Typical apatite structures were obtained for all coatings after dipping and subsequent heat treatment at 500 degrees C. The films obtained were uniform and dense, with a thickness of approximately 5 microm. The dissolution rate of the coating layer decreased with increasing F- incorporation within the apatite structure, which demonstrates the possibility of tailoring the solubility by a functional gradient coating of HA and FHA. The cell proliferation rate on the coating layer decreased slightly with increasing F- incorporation. The alkaline phosphatase (ALP) activity of the cells on all the HA and FHA coated samples showed much higher expression levels compared to pure Ti. This confirmed the improved activity of cell functions on the substrates with the sol-gel coating treatment.

Adsorption↗

Calcium phosphates and glass composite coatings on zirconia for enhanced biocompatibility.

Calcium phosphates (CaP) and phosphate-based glass (P-glass, xCaO-(0.55-x) Na(2)O-0.45P(2)O(5) composition) composite coatings were obtained on a strong ZrO(2) to improve biocompatibility, the mechanical strength and biological activity. Hydroxyapatite (HA) and P-glass mixed powder slurries were coated on the ZrO(2) substrate, and subsequently heat-treated to obtain CaP- and P-glass composite coatings. The effects of glass composition (x=0.3, 0.4, 0.5 mol), mixing ratio of glass to HA (30%, 40%, 50% wt/wt), and heat treatment temperature (800 degrees C, 900 degrees C, 1000 degrees C) on the coating properties were investigated. After heat treatment, additional calcium phosphates, i.e., dicalcium phosphate (DCP) and tricalcium phosphate (TCP), were crystallized, resulting in the formation of triphasic calcium phosphates (HA-TCP-DCP) surrounded by a glass phase. The relative amounts of the crystalline phases varied with coating variables. The higher heat treatment temperature and glass amount, and the lower CaO content in the glass composition rendered the composite coatings to retain the higher amounts of TCP and DCP while the initial HA decreased. These appearance of additional crystalline phases and reduction of HA amount were attributed to the combined effects, i.e., the melting-crystallization of P-glass and the reaction between glass liquid phase and HA powder during thermal treatment. As a result of the glass phase in the composite coatings, their microstructures became much denser when compared to the pure HA coating. In particular, a completely dense structure was obtained at coating conditions with large amount of glass addition (50 wt%) at the glass composition of lower CaO content (0.3 mol CaO), and the following heat treatment above 800 degrees C for 2h. As a result, the adhesion strengths of the composite coating layers were significantly improved when compared to the pure HA coating. The highest strength of the composite coating was approximately 40 MPa, an improvement of approximately 80% with respect to the pure HA coating. The composite coatings showed much higher dissolution rates than the pure HA coating due to the newly formed crystallines (TCP and DCP) and the remaining glass phase. The osteoblast-like cells grew and spread actively on the composite coating samples. The proliferation numbers and alkaline phosphate (ALP) activities of the cells on the composite coatings were improved by approximately 30-40% when compared to Thermanox control and ZrO(2) substrate, and were comparable to the pure HA coating. These findings suggested that the CaP and P-glass composites are potentially useful for hard tissue coating system, due to their morphological and mechanical integrity, enhanced bioactivity, and favorable responses to the osteoblast-like cells.

Adhesiveness↗

Strontium substituted calcium phosphate biphasic ceramics obtained by a powder precipitation method.

Strontium (Sr) substituted calcium phosphate ceramics were fabricated using a powder precipitation method. The Sr ions were added up to 8 mol % to replace the Ca ions during the powder preparation. Composition analysis showed that the added Sr was not fully incorporated within the as-precipitated apatite structure, presumably being washed out during the powder preparation. After calcination, the Sr containing powders were crystallized into apatite and tricalcium phosphate (TCP), that is, biphasic calcium phosphates were formed. The amount of TCP increased with increasing the Sr addition. The lattice parameters of the calcined powders increased gradually with Sr substitution in both the a- and c-axis. However, the obtained values deviated slightly from the calculated ones at higher Sr additions (>4%) due to the partial substitution of Sr ions. The microstructure of the sintered bodies changed with the Sr addition due to the formation of TCP. The Vickers hardness increased slightly from 5.2 to 5.5 MPa with increasing Sr addition, which was driven by the HA+TCP biphasic formation. The osteoblast-like cells cultured on the Sr-substituted biphasic sample spread and grew actively. The proliferation rate of the cells was higher in the samples containing more Sr. The alkaline phosphate activity of the cells was expressed to a higher degree with increasing Sr addition. These observations confirmed the enhanced cell viability and differentiation of the Sr-substituted biphasic calcium phosphate ceramics.

Alkaline Phosphatase↗

Porous ZrO2 bone scaffold coated with hydroxyapatite with fluorapatite intermediate layer.

Highly porous zirconia (ZrO(2)) bone scaffolds, fabricated by a replication technique using polymeric sponge, were coated with hydroxyapatite (HA). To prevent the chemical reactions between ZrO(2) and HA, an intermediate fluorapatite (FA) layer was introduced. The strength of the porous ZrO(2) was higher than that of pure HA by a factor of 7, suggesting the feasibility of ZrO(2) porous scaffolds as load-bearing part applications. The coated HA/FA layer, with a thickness of about 30 microm, was firmly adhered to the ZrO(2) body with a bonding strength of 22MPa. The osteoblast-like cells were attached and spread well on the coating layer throughout the porous scaffolds. The alkaline phosphatase activity of the proliferated cells on the HA/FA coated ZrO(2) was comparable to that on pure HA and higher than that on pure ZrO(2).

Alkaline Phosphatase↗