科技部補助專題研究計畫成果報告期末報告

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科技部補助專題研究計畫成果報告期末報告

應用電化學陰極沉積鈣磷處理提升具超低彈性係數新型Ti-Nb- Zr-Sn鈦合金表面之骨細胞相容性質

計畫類別：個別型計畫

計畫編號： MOST 104-2221-E-040-003- 執行期間： 104年08月01日至105年07月31日執行單位：中山醫學大學牙醫學系（所）

計畫主持人：李慈心共同主持人：黃何雄

計畫參與人員：博士班研究生-兼任助理人員：劉珈妃

報告附件：出席國際學術會議心得報告國際合作計畫研究心得報告

中　華　民　國　105　年　11　月　15　日

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中文摘要：在生醫植入材應用研究中，Ti-24Nb-4Zr-8Sn（Ti2448）是一種新型 β-Ti合金，由無毒元素組成且具有與骨組織相近的低彈性係數(約 45 GPa)。然而，Ti2448合金的耐蝕性和生物相容性仍需要進一步提升以達成臨床長期使用成功的需求。在本研究中，將Ti2448合金浸泡在含有鈣磷成分的溶液中進行簡單且快速的電化學陽極氧化處理

，改變其表面特性以提高其耐蝕性和生物活性。陽極氧化處理於 Ti2448合金表面產生具混合形貌的氧化層（厚度50-120 nm），外層為含有鈣磷成分的奈米多孔形貌(鈣磷比約1.5)，而內層靠近基材底部則為較緻密的內層氧化層。實驗結果顯示，此內部緻密氧化層能有效提高Ti2448合金的耐蝕性。此外，此外層含有鈣磷的奈米多孔形貌表現與各種生物物質相近的尺寸形貌，進而有效提升Ti2448合金表面潤濕性和蛋白質吸附的能力。根據上述結果，具有低彈性係數的陽極氧化Ti2448合金具有應用於臨床骨科的潛力。

中文關鍵詞： Ti-Nb-Zr-Sn合金、低彈性係數、電化學處理、鈣/磷、腐蝕、骨細胞反應

英文摘要： Ti-24Nb-4Zr-8Sn (Ti2448) is a new β-type Ti alloy which consists of nontoxic elements and exhibits exceptional low elastic modulus around 45 GPa for biomedical implant

applications. Nevertheless, the corrosion resistance and biocompatibility of Ti2448 alloys need to be improved for long-term clinical use. In this study, a simple and fast electrochemical anodization treatment in Ca/P-containing solution was used on Ti2448 alloys to enhance bio-corrosion resistance and biological responses of Ti2448 alloys via altering the surface characteristics of it. The anodization process produced a thicker oxide layer (50-120 nm)

composing of two different sections, one was outer section with Ca/P-containing nanoporous topography (Ca/P ratio 1.5) and the other was inner dense section near the

substrate. The results showed that the inner dense section of oxide layer obviously enhanced the bio-corrosion

resistance of Ti2448 alloys. Moreover, the Ca/P-containing nanoporous topography showing the similar scale of various biological species significantly improved the wettability and protein adsorption. In terms of above results, the anodized Ti2448 alloys with low elastic modulus have a potential for orthopedic applications.

英文關鍵詞： Ti-Nb-Zr-Sn alloy, low elastic modulus, electrochemical treatment, Ca/P, corrosion, bone cell response.

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Content

摘要 ………... 2

Abstract ………... 2

1. Introduction (including literature survey and study purpose) ………... 3 2. Materials and Methods ………... 5

3. Results ………... 7

4. Discussion ………... 9

5. Conclusions and Suggestions ………... 12

6. References ………... 13

7. Figures ………... 17

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摘要

在生醫植入材應用研究中，Ti-24Nb-4Zr-8Sn（Ti2448）是一種新型β-Ti 合金，由無毒元素組成且具有與骨組織相近的低彈性係數(約 45 GPa)。然而，Ti2448 合金的耐蝕性和生物相容性仍需要進一步提升以達成臨床長期使用成功的需求。

在本研究中，將 Ti2448 合金浸泡在含有鈣磷成分的溶液中進行簡單且快速的電化學陽極氧化處理，改變其表面特性以提高其耐蝕性和生物活性。陽極氧化處理於 Ti2448 合金表面產生具混合形貌的氧化層（厚度 50-120 nm），外層為含有鈣磷成分的奈米多孔形貌(鈣磷比約 1.5)，而內層靠近基材底部則為較緻密的內層氧化層。實驗結果顯示，此內部緻密氧化層能有效提高 Ti2448 合金的耐蝕性。

此外，此外層含有鈣磷的奈米多孔形貌表現與各種生物物質相近的尺寸形貌，進而有效提升 Ti2448 合金表面潤濕性和蛋白質吸附的能力。根據上述結果，具有低彈性係數的陽極氧化 Ti2448 合金具有應用於臨床骨科的潛力。

關鍵字：Ti-Nb-Zr-Sn 合金、低彈性係數、電化學處理、鈣/磷、腐蝕、

骨細胞反應。

Abstract

Ti-24Nb-4Zr-8Sn (Ti2448) is a new β-type Ti alloy which consists of nontoxic elements and exhibits exceptional low elastic modulus around 45 GPa for biomedical implant applications. Nevertheless, the corrosion resistance and biocompatibility of Ti2448 alloys need to be improved for long-term clinical use. In this study, a simple and fast electrochemical anodization treatment in Ca/P-containing solution was used on Ti2448 alloys to enhance bio-corrosion resistance and biological responses of Ti2448 alloys via altering the surface characteristics of it. The anodization process produced a thicker oxide layer (50-120 nm) composing of two different sections, one was outer section with Ca/P-containing nanoporous topography (Ca/P ratio  1.5) and the other was inner dense section near the substrate. The results showed that the inner dense section of oxide layer obviously enhanced the bio-corrosion resistance of Ti2448 alloys.

Moreover, the Ca/P-containing nanoporous topography showing the similar scale of various biological species significantly improved the wettability and protein adsorption.

In terms of above results, the anodized Ti2448 alloys with low elastic modulus have a potential for orthopedic applications.

Key words：Ti-Nb-Zr-Sn alloy, low elastic modulus, electrochemical treatment, Ca/P, corrosion, bone cell response.

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1. Introduction (including literature survey and study purpose)

More than millions of bone graft procedures are expected to be performed yearly to fill bone defects or improve fracture healing and repair. This number is expected to continue to increase with the rapid growth of the elderly population. Therefore, developing a suitable material for repairing and regenerating bones that have been fractured due to disease, trauma and aging is a significant clinical challenge¹. Titanium (Ti) and Ti-based alloys are widely used as biomaterials for orthopedic and dental implant applications due to their suitable mechanical properties, exceptional corrosion resistance and the highest biocompatibility with bone among all metallic biomaterials^2,3. Although Ti and Ti-based alloys have specific and excellent properties for biomedical applications, some problems must be addressed for the long-term implantation of these materials. One of the most important issues is biomechanical incompatibility, especially in the elastic modulus of the commercially used Ti and Ti-based alloys, with human bone because both bone overload and excessive stress protection can result in bone resorption^4,5.

Compared with conventional metallic materials, such as stainless steel and Co-Cr- Mo alloys, Ti and Ti-based alloys show a relatively lower elastic modulus than those of stainless steel (200 GPa) and Co-Cr-Mo alloys (200-230 GPa). However, the elastic modulus of most of the commonly used commercial Ti and Ti-based alloys, including commercially pure Ti (CP-Ti), Ti-6Al-4V and Ti-6Al-7Nb (100-110 GPa)⁶, is still an order of magnitude higher than that of human cortical bone (10-30 GPa)^7,8. This mismatch between the elastic modulus of bone and that of implants will cause an insufficient load transfer from the implant to the adjacent bone and thus induce a stress- shielding effect during long-term implantation at the sites of load-bearing bones. This type of stress-shielding effect will lead to bone resorption at the bone-implant interface and eventually result in implant failure^9,10.

β-type Ti alloys have been the most attractive materials, for overcoming the incompatibility between the elastic modulus of Ti-based implants and that of bone, for orthopedic applications due to their non-toxic components, high mechanical strength and low elastic modulus^3,11,12. Of all β-type Ti alloys, Ti-24Nb-4Zr-8Sn (wt%, hereafter designated Ti2448) is a recently developed β-type Ti alloy for biomedical applications.

This novel alloy consists of non-toxic and non-allergic elements and possesses a low elastic modulus of approximately 45 GPa^13,14, close to that of human cortical bone.

Such a low elastic modulus may prevent the stress-shielding effect caused by the inhomogeneous stress transfer between metal implants and the adjacent bone.

Furthermore, this alloy not only has a low elastic modulus that is close to that of human bone, but it also has high mechanical strength - an ideal combination/balance of properties that is not available in the other β-type Ti alloys that have been developed so

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far.

For long-term clinical use, the corrosion resistance of metallic materials is a great concern, especially when a metallic substitute is implanted in the virulent electrolytic environment of the human body, because corrosion is a gradually degradation of materials by electrochemical attack. Therefore, the corrosion performance of Ti2448 is extremely important for orthopedic and dental implant applications. Cheng et al.

reported that for dental implant applications, the Ti2448 alloy showed a corrosion resistance similar to that of CP-Ti and the Ti6Al4V alloy in simulated oral environments, such as modified Fusayama artificial saliva and a lactic acid solution¹⁵. Moreover, Bai et al. showed that the corrosion resistance of the Ti2448 alloy was better than that of Ti6Al4V but comparable to that of CP-Ti in different simulated physiological solutions^16,17. It has been commonly accepted that Ti and Ti-based alloys show exceptional corrosion resistance due to the natural formation of a passive oxide film.

However, this protective passive film, which inhibits the release of metal ions, may become unstable in the human body due to deterioration during long-term implantation.

Once the passive surface film is disrupted, corrosion proceeds, and metal ions are released continuously, which leads to ion accumulation and thus results in biological side effects and eventually implant failure^18,19. Although the corrosion behavior of the Ti2448 alloy is similar to that of Ti, there is still a potential risk of metal ion release from the Ti2448 alloy due to the corrosion process. Therefore, determining how to further improve the bio-corrosion resistance of the Ti2448 alloy for future long-term implantation is one of the important purposes of this study.

Moreover, the passive oxide film on metallic materials plays an influential role not only in corrosion resistance but also in the biocompatibility of materials. It is well known that surface properties, including surface topography, roughness, chemical composition and wettability, are important factors in biocompatibility because they affect the biological responses at the bone-implant interface^20,22. Surface topography is a key surface property because it is able to regulate the responses of cells that are located on material surfaces. Some studies have reported the design and creation of surface geometries with a suitable nanoscale topography that were able to improve cell responses, such as cell adhesion²³, migration²⁴, proliferation²⁵ and differentiation²⁶. There are various surface modification treatments that can create a nanoscale topography on a metallic material surface to provide the desired biological responses.

In our previous studies, a fast and simple electrochemical anodization treatment was used to produce a nano-networked oxidelayer on the surfaces of CP-Ti and Ti-based alloys to improve the hemocompatibility and cell responses. Moreover, the layer was also able to enhance the corrosion resistance of biomedical Ti alloys^27-29.

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Our hypothesis is that a Ca/P-containing oxide layer with a nanoscale porous topography could be produced and thickened on the surface of the Ti2448 alloy using a simple and fast electrochemical anodization treatment in Ca/P-containing solution to improve the bio-corrosion resistance and biocompatibility of this new β-type Ti alloy with low elastic modulus. To analyze this hypothesis, the polished Ti2448 specimens were created, as well as polished Ti control specimens, and Ti2448 specimens treated with electrochemical anodization treatment in Ca/P-containing solution to produce a nanoscale porous topography containing Ca/P composition. Within this research, the surface characteristics, including the surface morphology, oxide layer thickness, crystal structure and surface wettability, were investigated after the anodization treatment.

Furthermore, the corrosion behaviors of the anodized Ti2448 alloys in simulated body environments were evaluated. To provide helpful indicators for further in vivo studies and clinical applications, the protein adsorption of the anodized Ti2448 alloy was studied as well.

2. Materials and Methods

2.1 Specimen preparation

Discs (diameter of 15 mm; thickness of 1 mm) of Ti2448, the new β-type of Ti alloys, which were polished with SiC papers from #120 up to #1200 and then cleaned in ethyl alcohol were used as substrates. Pure commercial Ti disks (diameter of 15 mm;

thickness of 1 mm) that were polished and cleaned according to the above-mentioned procedure were used as a reference control.

A potentiostat was used for the electrochemical anodization treatment to apply two different anodic currents, A1 and A2 (A1< A2 < 0.5 ampere), to the polished Ti2448 substrate for a few tens of min in Ca/P-containing alkaline solution (Ca⁺²< 0.5M; PO4- 3 < 0.5M). The polished Ti and Ti2448 specimens that were not subjected to the electrochemical anodization treatment were termed Ti-M and Ti2448-M, respectively.

The polished Ti2448 specimen treated by electrochemical anodization with the applied currents A1 and A2 were termed Ti2448-A1 and Ti2448-A2, respectively.

2.2 Surface characteristics analysis

The surface morphology and average roughness of the test specimens were evaluated using field emission scanning electron microscopy (FE-SEM) and atomic force microscopy (AFM), respectively. The crystallographic structure and thickness of the outermost surface layer of the anodized Ti2448 specimens were evaluated using transmission electron microscopy (TEM). Prior to the TEM evaluation, the cross- sectional test specimens were prepared using a focused ion beam milling process. The

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chemical composition of the outer surface layer of the specimens was analyzed by X- ray photoelectron spectroscopy (XPS). The surface wettability of the test specimens was analyzed using a contact angle goniometer, and the surface free energy of the specimens was calculated with two different solutions: polar double-distilled H2O and non-polar diiodomethane.

2.3 Bio-corrosion resistance analysis

The surface corrosion resistance of the polished Ti-M and Ti2448-M and the electrochemical anodization-treated Ti2448-A1 and Ti2448-A2 was evaluated using a potentiostat. A saturated calomel electrode (SCE) and a platinum sheet were used as the reference and counter electrode, respectively. The test specimens with and without the electrochemical anodization treatment were used as the working electrodes. Neutral simulated blood plasma (SBP; pH 7.4)³⁰ and modified Fusayama artificial saliva (AS;

pH 5.2)³¹ were used as the corrosion test electrolyte and were maintained at 37°C during the experiment. The SBP was used to simulate the environment inside human body, and the AS was used to simulate that of the human mouth. All test specimens were placed into two different electrolytes, and the polarization curves of all specimens were measured from -1 V to + 1.5 V (with respect to the SCE).

2.4 Protein adsorption analysis

Two different types of protein were used as model proteins to evaluate the difference in protein adsorption on the test specimens. One was bovine serum albumin (BSA, Sigma), the most abundant protein in human body plasma³²; the other was fibronectin (Sigma), an important protein involved in cell adhesion, migration, proliferation and differentiation³³. The test specimens were immersed in two different phosphate buffered saline (PBS) solutions, one containing 5 mg/ml BSA and the other containing 50 μg/ml fibronectin. After 5 min of incubation at 37°C, the test specimens were washed with double-distilled H2O and then dried at room temperature. XPS was used to analyze the nitrogen spectra (in terms of N1s) of the test specimens to estimate the ability for proteins to adsorb on the various treated test specimens.

2.5 Statistical analysis

The number of samples was 3 for all measurements, and the results were expressed as the means ± standard deviation (SD). Student’s two-tailed t-test was used to determine the level of the significance, and p<0.05 was considered statistically significant.

3. Results

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3.1 Surface characteristics

The surface morphologies of Ti2448 before and after the electrochemical anodization treatment are shown in Fig. 1. The FE-SEM images of the polished Ti (Ti- M) and Ti2448 (Ti2448-M) only showed oriented polished grooves (Fig. 1a and 1b).

After the electrochemical anodization treatment, a nanoscale porous oxide layer was formed on the anodized Ti2448 (Ti2448-A1 and Ti2448-A2) surface (Fig. 1c and 1d).

The pore size of the porous oxide layer on the Ti2448-A1 and Ti2448-A2 ranged from a few nm to 50 nm; however, Ti2448-A2, which was treated with a larger anodic current for a longer time, showed a bigger pore size than that of Ti2448-A1. XPS analysis results showed that the chemical compositions of Ti-M, Ti2448-A1, and Ti2448-A2 were the same, and mainly contained TiO2 and Nb2O5 with small amounts of ZrO2 and SnO2. Moreover, the XPS depth profiles, in terms of the atomic concentrations of O, Ti, Nb, Zr, Sn in the surface of the test specimens indicated that the electrochemical anodization treatment significantly increased the thickness of the surface oxide layer.

The ratio of Ca/P on the electrochemically treated Ti 2448-A1 and Ti2448-A2 surfaces was close to 1.5.

Furthermore, the thickness and crystal structure of the nanoporous oxide layer on Ti2448-A1 and Ti2448-A2 were analyzed by TEM and are shown in Fig. 2. The TEM images indicate that the cross-sectional thickness of the nanoscale porous oxide layer on Ti2448-A1 and Ti2448-A2 was approximately 50 to 80 nm and 80 to 120 nm, respectively (Fig. 2a and 2b). Compared with the untreated Ti-M and Ti2448-M, the treated Ti2448-A1 and Ti2448-A2 exhibited significant thickening of the surface oxide layer. The crystal structure of the oxide layer was amorphous. The oxide layer could be separated into two different sections: the outer porous section close to the surface and the inner nonporous section between the substrate and the outer porous section.

Compared with the outer section, the inner section had a structure that was tighter with higher density (Fig. 2c).

AFM was used to evaluate the effect of the anodization treatment on the surface roughness of Ti2448-A1 and Ti2448-A2. The evaluation showed that there were no significant differences in surface roughness between the treated and untreated test samples (Fig. 3). For all test samples, the average surface roughness (Ra) was approximately 0.1 µm.

Finally, a contact angle goniometer was used to image and calculate the contact angle and surface free energy to evaluate the wettability of the test samples. The result shown in Fig. 4 indicates that the polar double-distilled H2O on the anodized Ti2448- A1 and Ti2448-A2 showed a smaller contact angle (11-16°) than that on the untreated Ti-M and Ti2448-M (＞56°). In contrast, the surface free energies of Ti2448-A1 and Ti2448-A2 were much higher than those of the untreated groups, suggesting that

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Ti2448-A1 and Ti2448-A2 exhibited better surface wettability than that of Ti-M and Ti2448-M.

The above-mentioned results indicate that the electrochemical anodization treatment did not change the surface roughness on the µm scale, but it successfully created a hydrophilic double oxide layer which consists of outer nanoporous section and inner dense section.

3.2 Bio-corrosion resistance

The polarization curves for Ti-M, Ti2448-M, Ti2448-A1 and Ti2448-A2 are shown in Fig. 5. Compared to the corrosion potential (Ecorr) of the untreated Ti-M and Ti2448-M, the Ecorr of Ti2448-A1 and Ti2448-A2 was shifted to much nobler values.

In addition, in the passive region, when the same anodic voltage was applied to the specimens, the anodic current (Ipass) of Ti2448-A1 and Ti2448-A2 was approximately ten times smaller than that of Ti-M and Ti 2448-M. In the SBP solution, the values of the corrosion rate (Icorr) for Ti-M, Ti2448-M, Ti2448-A1 and Ti2448-A2 were 0.041, 0.102, 0.019 and 0.023 μA/cm², respectively. In the AS solution, the Icorr values of Ti- M, Ti2448-M, Ti2448-A1 and Ti2448-A2 were 0.028, 0.093, 0.040 and 0.066 μA/cm², respectively. In both the SBP and AS solutions, the Icorr of the anodized Ti2448 group was smaller than that of the untreated Ti2448. The above-mentioned results suggest that the amount of total ions released by Ti2448-A1 and Ti2448-A2 was lower than that from either Ti-M or Ti2448-M, indicating that the thickened oxide layer produced by the electrochemical anodization treatment provided better protection than that of the untreated group.

3.3 Protein adsorption ability

Protein adsorbed on the surface of material is the very beginning step before cells attachment. Moreover, it might affect the following cell responses especially cell adhesion. Therefore, the protein adsorption, in terms of nitrogen (N1s) on all test specimens was measured using XPS and was shown in Fig. 6. The result indicated that the treated Ti2448-A1 and Ti2448-A2 showed higher N1s intensities than the untreated Ti-M and Ti2448-M in both the albumin (Fig. 6(a)) and fibronectin (Fig. 6(b)) solutions.

The amount of albumin and fibronectin adsorbed on the Ti2448-A1 and Ti2448-A2 was more than 1-3 times then that on the untreated Ti-M and Ti2448-M, indicating that the electrochemical anodized treatment could improve the protein adsorption ability of Ti2448 alloy.

4. Discussion

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For long-term clinical use, the corrosion resistance of the Ti2448 alloy is a great concern, especially when the Ti2448 alloy is implanted in the virulent electrolytic environment of the human body. The results of this study showed that the corrosion resistance of the Ti2448 alloy could be significantly enhanced through an electrochemical anodization treatment due to the formation of dense inner oxide layer on the substrate (Fig. 5).

It has been commonly accepted that the passive oxide film formed on the surface of metallic materials plays an important role in corrosion resistance. In previous studies, Cheng et al. reported that the Ti2448 alloy showed the lower total metal ions release than that of CP-Ti and Ti6Al4V alloy in static immersion test in AS, lactic acid solution, fluoridated saliva and fluoridated acidified saliva. This indicated that Ti2448 alloy had better performance of corrosion resistance than that of CP-Ti and Ti6Al4V alloy for dental implant applications¹⁵. In contrast, Bai et al. indicated that the Ti2448 alloy exhibited a wider passive region than that of CP-Ti and Ti6Al4V alloy and its corrosion current density was comparable to that of CP-Ti in PBS, Hank’s solution and AS solution^16,17.

As shown in Fig. 5, Ti2448-M showed a corrosion resistance comparable to that of Ti-M in both SBP and AS solutions. Furthermore, the anodized Ti2448 alloys showed much better corrosion resistance than that of Ti-M and Ti2448-M (Fig. 5). This exceptional bio-corrosion resistance of the anodized Ti2448 alloys may be due to the protective oxide film formed on the surface of it. The passivity and corrosion resistance of many pure metals used for biomedical applications have been studied. The results showed that Ti, Nb, Zr and Sn metals exhibited great corrosion resistance and in the following order: Nb>Ti>Zr>Sn^36,37. Moreover, several studies also concluded that the addition of Nb and Zr improves the corrosion resistance of Ti alloys because of the formation of Nb2O5 and ZrO2,whichcan strengthen the TiO2 oxide film on Ti alloys^38-

40. Based on the above-mentioned studies, the surface oxide film of Ti2448-M, Ti2448- A1 and Ti2448-A2, which contains corrosion-resistant components (e.g., mainly TiO2

and Nb2O5 with small amounts of ZrO2 and SnO), can provide Ti2448 alloy with good corrosion resistance.

The corrosion resistance of Ti and Ti alloys depends not only on the composition of the surface oxide film but also on their thickness and crystal structure. It is well known that the surface oxide film which spontaneously forms on Ti and Ti alloys is thin (<10 nm), uniform and dense⁴¹. Therefore, any surface treatments that can thicken this protective oxide film were expected to improve the corrosion resistance of Ti and Ti alloys. Cigada et al. used anodic oxidation to improve the corrosion resistance of Ti6Al4V alloy in buffered physiological solution by thickening the oxide film on the Ti6Al4V alloys⁴². Other research from Birch et al. and Velten et al. also showed that

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oxide films thickened by thermal oxidation, anodic oxidation or sol-gel coating exhibits better corrosion resistance than that of polished Ti and Ti alloys^{41, 43}.

As shown in Fig. 2, the surface oxide film on Ti2448-A1 and Ti2448-A2 was approximately 50-80 nm and 80-120 nm thick, respectively. The anodization treatment significantly thickened the passive oxide film on Ti2448-A1 and Ti2448-A2 compared with that spontaneously formed on Ti-M and Ti2448-M. In contrast with the naturally forming dense oxide film on Ti and Ti alloys surface, the protective oxide film formed on the anodized Ti2448 alloys exhibited a nanoscale porous surface topography with a pore size that ranged from a few to 50 nm (Fig. 1c and 1d). Although the oxide layer on the anodized Ti2448 alloys showed a porous surface topography, the TEM analysis demonstrated that this oxide film could be separated into two sections. One was the outer porous section close to the outer most surface, and the other was the inner nonporous dense section between the substrate and the outer porous section. Compared with the outer section, the inner section of the anodized Ti2448 alloys had denser and tighter structure which contributed to the improvement of the corrosion resistance of Ti2448 alloy. Therefore, the existence of this thicker, dense, inner section of oxide film improves the corrosion resistance of Ti2448 alloys in both SBP and AS solutions.

Furthermore, the crystal structure of this inner section was amorphous. Amorphous oxide structures lack grain boundaries make it difficult for electrochemical corrosion⁴⁴. Therefore, many studies have demonstrated that an amorphous oxide film could improve the corrosion resistance of metal materials^44-46. The above-mentioned results are consistent with the results of this study: the potential dynamic polarization curves of the anodized Ti2448 alloys with the thicker and inner dense amorphous oxide layer displayed higher Ecorr, lower values of anodic current density and lower Icorr than those of the untreated Ti2448-M (Fig. 5).

According to previous study, the Ti2448 alloy, which consists of non-toxic, non- allergic elements and possesses a low elastic modulus of approximately 45 GPa¹³, has properties that are beneficial for biomedical applications. The low elastic modulus of the Ti2448 alloy may balance the inhomogeneous transfer of stress between the metal implant and the adjacent bone, thus further preventing the stress-shielding effect. For future clinical application, bio-corrosion resistance of the Ti2448 alloy and good bio- interaction between tissue and the Ti2448 alloy will both be a great concern. In the previous studies, many surface modified treatments have been used to enhance the biocompatibility of biomaterials. In studies of Ti2448 alloy, many previous researches used micro-arc oxidation (MAO) treatment to modify the surface topography and chemical composition of the Ti2448 alloy to improve its biological responses^47-49. However, the MAO treatment combines electrochemical oxidation with a high-voltage spark treatment in an electrolyte solution. The high voltages used in the above-

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mentioned studies all exceeded 200 V, and the high energy made the process relatively dangerous and expensive. In contrast with the MAO treatment, the electrochemical anodization treatment used in this study is safer and cheaper. Moreover, the bio- corrosion resistance and biocompatibility of the Ti2448 alloy was significantly improved through the simple and fast electrochemical anodization treatment in this study.

It is commonly accepted that surface properties, such as topography, roughness, chemical composition and wettability, affect the biological responses at the bone- implant interface. Surface topography is a key property because it is able to regulate the responses of cells on the materials surface. In previous studies, nanoscale topographies, such as nanotubes, nanopits and nanonetworks, have influenced cell adhesion, spreading, migration, proliferation and differentiation in vitro, as well as bonding strength and bone formation in vivo^50-53. In the present study, a disordered but homogeneous nanoscale porous oxide layer could be created on the surface of Ti2448 alloys through the electrochemical anodization treatment and the chemistry of the oxide layer was similar to that of previously used materials. The pore size of the porous oxide layer on the anodized Ti2448 alloys ranged from a few nm to 50 nm (Fig. 1c and 1d).

Ti2448-A2 showed a bigger pore size than that of Ti2448-A1 due to the difference in the applied anodic current. Moreover, Ti2448-A1 and Ti2448-A2 showed little difference in their nanofeatures. According to the previous report by Rani et al., the nanofeature of Ti2448-A1 was more similar to a nanoleaf, and that of Ti2448-A2 was more similar to a nanoscaffold⁵⁴. The surface free energy of the anodized Ti2448 alloys was enhanced, regardless of the difference in their nanofeatures. The results of contact angle and surface free energy analysis suggested that Ti2448-A1 and Ti2448-A2 showed better surface wettability than Ti-M and Ti2448-M. Bico et al. concluded that surface wettability could be affected by the surface chemistry and topography⁵⁵. In our research, the Ti2448-M, Ti2448-A1 and Ti2448-A2 alloys exhibited similar surface chemistries but different surface topographies. Therefore, we suggest that the improved surface wettability caused by the electrochemical anodization treatment was mainly due to formation of the nanoscale porous topography surface oxide layer. In contrast, it has been reported that the cell attachment and spreading were significantly greater on hydrophilic surfaces than on hydrophobic surfaces⁵⁶. Therefore, we expected that this hydrophilic surface of Ti2448-A1 and Ti2448-A2 could result in easy penetration by body fluids, thereby enhancing the protein adsorption to trigger the subsequent cell responses.

Protein adsorption is the first step that occurs when a biomaterial is implanted into a biological environment, and it is a key determinant of the responses of cells to the material surface. As shown in Fig. 6, the amount of albumin and fibronectin adsorbed

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on Ti2448-A1 and Ti2448-A2 was more than 1- to 3 fold higher than the amount adsorbed on the untreated Ti-M and Ti2448-M. In previous studies, one mechanism of protein adsorption was the electrostatic interaction between proteins and the material surface⁵⁷. The isoelectric point of TiO2 and Nb2O5, the two main component of the surface oxide layer of the anodized Ti2448 alloys, is approximately 4.1 to 4.5, which is less than the pH of the physiological environment (~pH 7.0) and makes the oxide surface negatively charged^58,59. Therefore, the negatively charged surface could attract positively charged ions, such as Ca²⁺. When Ca²⁺ ions bind to the material surface, they could act as a bridge between the negatively charged metal oxide surface and proteins to induce protein adsorption onto the material surface.

In addition, surface topographical characteristics are also important factors and influence the protein adsorption. Sela et al. reported that the preferential adsorption of plasma protein may be explained by the increase in the 3D surface area of the modified Ti surface⁶⁰. Richert et al. also reported that the greater surface area resulting from the creation of the nanoporous structure provides more binding sites for protein adsorption⁶¹. In this study, the nanoscale porous oxide layer produced by the electrochemical anodization treatment was negatively charged and hydrophilic, and its surface area was expected to be much larger than that of untreated groups. These changes significantly enhanced the protein adsorption ability of Ti2448 alloys. This finding is consistent with the above-mentioned researches. This behavior may trigger the subsequent cell adhesion, proliferation, migration and differentiation^62-64.

5. Conclusions and Suggestions

In the one-year project, using a simple and fast electrochemical anodization treatment, a nanoporous oxide multilayer could be successfully produced and thickened on the surface of the newly developed -type Ti-24Nb-4Zr-8Sn (Ti2448) alloy with a low elastic modulus of 45 GPa. The dense inner section of the nanoporous oxide multilay er resulted in enhanced resistance to bio-corrosion. This resistance was demonstrated by an increase in the corrosion potential and a decrease in the anodic current in both the SBP and AS conditions. We suggest that the presence of the nanoporous oxide multilayer provides excellent protection for the substrate. This layer prevents ion release from the substrate and decreases the risk of cytotoxicity caused by metal ions accumulation during clinical implantations.

Moreover, the Ca/P-containing (ratio of Ca/P: 1.5) nanoporous outer section of the oxide multilayer also improved the surface wettability of the Ti2448 alloy. In addition to the improved hydrophilicity, this unique nanoporous topography has a range of pore sizes from a few nm up to approximately 50 nm; this range covers the scale of various

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types of proteins in the human body. From the results of this study, it is thus reasonable to conclude that the above-mentioned characteristics may enhance the protein adsorption ability of the Ti2448 alloy. Because of the improved bio-corrosion resistance and biological responses of the anodized Ti2448 alloys, we suggest that the surface- modified Ti2448 alloys with low elastic modulus have a great potential for biomedical implant applications. Further in vivo study on the osseointegration of the developed materials is suggested

6. References

[1] Fu, Q., Saiz, E., Rahaman, M. N., Tomsia, A. P. Bioactive glass scaffolds for bone tissue engineering: state of the art and future perspectives. Mater Sci Eng C Mater Biol Appl 31, 1245-56 (2011).

[2] Long, M., Rack, H. J. Titanium alloys in total joint replacement--a materials science perspective. Biomaterials 19, 1621-39 (1998).

[3] Niinomi, M. et al. Development of low rigidity β-type titanium alloy for biomedical applications. Mater Trans 43, 2970-7 (2002).

[4] Niinomi, M. Mechanical properties of biomedical titanium alloys. Mater Sci Eng A Struct Mater 243, 231-6 (1998).

[5] Learmonth, I. D. Biocompatibility: a biomechanical and biological concept in total hip replacement. Surgeon 1, 1-8 (2003).

[6] Navarro, M., Michiardi, A., Castano, O., Planell, J. A. Biomaterials in orthopaedics. J R Soc Interface 5, 1137-58 (2008).

[7] Rho, J. Y., Kuhn-Spearing, L., Zioupos, P. Mechanical properties and the hierarchical structure of bone. Med Eng Phys 20, 92-102 (1998).

[8] Murr, L. E. et al. Microstructure and mechanical properties of open-cellular biomaterials prototypes for total knee replacement implants fabricated by electron beam melting. J Mech Behav Biomed Mater 4, 1396-411 (2011).

[9] Bobyn, J. D., Glassman, A. H., Goto, H., Krygier, J. J., Miller, J. E., Brooks, C. E.

The effect of stem stiffness on femoral bone resorption after canine porous-coated total hip arthroplasty. Clin Orthop Relat Res 261, 196-213 (1990).

[10] Huiskes, R., Weinans, H., van Rietbergen, B. The relationship between stress shielding and bone resorption around total hip stems and the effects of flexible materials. Clin Orthop Relat Res 274, 124-34 (1992).

[11] Kuroda, D., Niinomi, M., Morinaga, M., Kato, Y., Yashiro, T. Design and mechanical properties of new beta type titanium alloys for implant materials.

Mater Sci Eng A Struct Mater 243, 244-9 (1998).

[12] Niinomi M. et al. Corrosion wear fracture of new β type biomedical titanium alloys.

Mater Sci Eng A Struct Mater 263, 193-9 (1999).

[13] Hao, Y. L., Li, S. J., Sun, S. Y., Zheng, C. Y., Yang, R. Elastic deformation behaviour of Ti-24Nb-4Zr-7.9Sn for biomedical applications. Acta Biomater 3, 277-86 (2007).

[14] Hao, Y. L., Li, S. J., Sun, B. B., Sui, M. L., Yang, R. Ductile titanium alloy with low poisson’s ratio. Phys Rev Lett 98, 216405 (2007).

[15] Cheng, Y., Hu, J., Zhang, C., Wang, Z., Hao, Y., Gao, B. Corrosion behavior of novel Ti-24Nb-4Zr-7.9Sn alloy for dental implant applications in vitro. J Biomed Mater Res B Appl Biomater 101, 287-94 (2013).

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[16] Bai, Y., Hao, Y. L., Li, S. J., Hao, Y. Q., Yang, R., Prima, F. Corrosion behavior of biomedical Ti-24Nb-4Zr-8Sn alloy in different simulated body solutions. Mater Sci Eng C Mater Biol Appl 33, 2159-67 (2013).

[17] Bai, Y., Li, S. J., Prima, F., Hao, Y. L., Yang, R. Electrochemical corrosion behavior of Ti–24Nb–4Zr–8Sn alloy in a simulated physiological environment. Appl Surf Sci 258, 4035-40 (2012).

[18] Mu, Y., Kobayashi, T., Sumita, M., Yamamoto, A., Hanawa, T. Metal ion release from titanium with active oxygen species generated by rat macrophages in vitro.

J Biomed Mater Res 49, 238-43 (2000).

[19] Huang, H. H. et al. Ion release from NiTi orthodontic wires in artificial saliva with various acidities. Biomaterials 24, 3585-92 (2003).

[20] Lim, J. Y., Liu, X., Vogler, E. A., Donahue, H. J. Systematic variation in osteoblast adhesion and phenotype with substratum surface characteristics. J Biomed Mater Res A 68, 504-12 (2004).

[21] Zhao, G. et al. High surface energy enhances cell response to titanium substrate microstructure. J Biomed Mater Res A 74, 49-58 (2005).

[22] Lim, J. Y., Donahue, H. J. Cell sensing and response to micro- and nanostructured surfaces produced by chemical and topographic patterning. Tissue Eng 13, 1879- 91 (2007).

[23] Biggs, M. J. et al. Interactions with nanoscale topography: adhesion quantification and signal transduction in cells of osteogenic and multipotent lineage. J Biomed Mater Res A 91, 195-208 (2009).

[24] Dalby, M. J., McCloy, D., Robertson, M., Wilkinson, C. D., Oreffo, R. O.

Osteoprogenitor response to defined topographies with nanoscale depths.

Biomaterials 27, 1306-15 (2006).

[25] Macak, J. M. et al. TiO2 nanotubes: Self-organized electrochemical formation, properties and applications. Curr Opin Solid State Mater Sci 11, 3-18 (2007).

[26] Zhao, L., Mei, S., Chu, P. K., Zhang, Y., Wu, Z. The influence of hierarchical hybrid micro/nano-textured titanium surface with titania nanotubes on osteoblast functions. Biomaterials 31, 5072-82 (2010).

[27] Yang, W. E., Huang, H. H. Improving the biocompatibility of titanium surface through formation of a TiO2 nano-mesh layer. Thin Solid Films 518, 7545-50 (2010).

[28] Huang, H. H., Chen, J. Y., Lin, M. C., Wang, Y. T., Lee, T. L., Chen, L. K. Blood responses to titanium surface with TiO2 nano-mesh structure. Clin Oral Implants Res 23, 379-83 (2012).

[29] Huang, H. H., Wu, C. P., Sun, Y. S., Lee, T. H. Improvements in the corrosion resistance and biocompatibility of biomedical Ti–6Al–7Nb alloy using an electrochemical anodization treatment. Thin Solid Films 528, 157-62 (2013).

[30] Oyane, A., Kim, H. M., Furuya, T., Kokubo, T., Miyazaki, T., Nakamura, T.

Preparation and assessment of revised simulated body fluids. J Biomed Mater Res A 65, 188-95 (2003).

[31] Widu, F., Drescher, D., Junker, R., Bourauel, C. Corrosion and biocompatibility of orthodontic wires. J Mater Sci Mater Med 10, 275-81 (1999).

[32] Andrade, J. D., Hlady, V. Plasma protein adsorption: the big twelve. Ann N Y Acad Sci 516, 158-72 (1987).

[33] Pankov, R., Yamada, K. M. Fibronectin at a glance. J Cell Sci 115, 3861-3 (2002).

[34] Hung, S. C., Chen, N. J., Hsieh, S. L., Li, H., Ma, H. L., Lo, W. H. Isolation and characterization of size-sieved stem cells from human bone marrow. Stem Cells 20, 249-58 (2002).

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[35] Perng, C. K. et al. Culturing adult human bone marrow stem cells on gelatin scaffold with pNIPAAm as transplanted grafts for skin regeneration. J Biomed Mater Res A 84, 622-30 (2008).

[36] Palit, G. C., Elayaperumal K. Passivity and pitting of corrosion resistant pure metals Ta, Nb, Ti, Zr, Cr and Al in chloride solutions. Corros Sci 18, 169-79 (1978).

[37] Pourbaix, M. Electrochemical corrosion of metallic biomaterials. Biomaterials 5, 122-34 (1984).

[38] Kobayashi, E., Wang, T. J., Doi, H., Yoneyama, T., Hamanaka, H. Mechanical properties and corrosion resistance of Ti–6Al–7Nb alloy dental castings. J Mater Sci Mater Med 9, 567-74 (1998).

[39] Mythili, R., Saroja, S., Vijayalakshmi, M., Raghunathan, V. S. Selection of optimum microstructure for improved corrosion resistance in a Ti–5%Ta–1.8%Nb alloy. J Nucl Mater 345, 167-83 (2005).

[40] Okazaki, Y., Tateishi, T., Ito, Y. Corrosion resistance of implant alloys in pseudo physiological solution and role of alloying elements in passive films. Mater Trans 38, 78-84 (1997).

[41] Birch, J. R., Burleigh, T. D. Oxides formed on titanium by polishing, etching, anodizing, or thermal oxidizing. Corrosion 56, 1233-41 (2000).

[42] Cigada, A., Cabrini, M., Pedeferri, P. Increasing of the corrosion resistance of the Ti6Al4V alloy by high thickness anodic oxidation. J Mater Sci Mater Med 3, 408- 12 (1992).

[43] Velten, D., Biehl, V., Aubertin, F., Valeske, B., Possart, W., Breme, J. Preparation of TiO2 layers on cp-Ti and Ti6Al4V by thermal and anodic oxidation and by sol- gel coating techniques and their characterization. J Biomed Mater Res A 59, 18- 28 (2002).

[44] Shih. C. C., Lin, S. J., Chung, K. H., Chen, Y. L., Su, Y. Y. Increased corrosion resistance of stent materials by converting current surface film of polycrystalline oxide into amorphous oxide. J Biomed Mater Res 52, 323-32 (2000).

[45] Shih, C. C., Shih, C. M., Su, Y. Y., Su, L. H. J., Chang, M. S., Lin, S. J. Effect of surface oxide properties on corrosion resistance of 316L stainless steel for biomedical applications. Corros Sci 46, 427-41 (2004).

[46] Jeong, H. Y., Kim, S. K., Lee, J. Y., Choi, S. Y. Impact of amorphous titanium oxide film on the device stability of Al/TiO2/Al resistive memory. Appl Phys A Mater Sci Process 102, 967-72 (2011).

[47] Gao Y. et al. Improved biological performance of low modulus Ti–24Nb–4Zr–

7.9Sn implants due to surface modification by anodic oxidation. Appl Surf Sci 255, 5009-15 (2009).

[48] Wu, J., Liu, Z. M., Zhao, X. H., Gao, Y., Hu, J., Gao, B. Improved biological performance of microarc-oxidized low-modulus Ti-24Nb-4Zr-7.9Sn alloy. J Biomed Mater Res B Appl Biomater 92, 298-306 (2010).

[49] Han, X. et al. In vitro biological effects of Ti2448 alloy modified by micro-arc oxidation and alkali heatment. J Mater Sci Technol 27, 317-24 (2011).

[50] Lim, J. Y. et al. The regulation of integrin-mediated osteoblast focal adhesion and focal adhesion kinase expression by nanoscale topography. Biomaterials 28, 1787- 97 (2007).

[51] Das, K., Bose, S., Bandyopadhyay, A. TiO2 nanotubes on Ti: Influence of nanoscale morphology on bone cell-materials interaction. J Biomed Mater Res A 90, 225-37 (2009).

[52] Chiang, C. Y. et al. Formation of TiO2 nano-network on titanium surface increases the human cell growth. Dent Mater 25, 1022-9 (2009).

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[53] Bjursten, L. M., Rasmusson, L., Oh, S., Smith, G. C., Brammer, K. S., Jin, S.

Titanium dioxide nanotubes enhance bone bonding in vivo. J Biomed Mater Res A 92, 1218-24 (2010).

[54] Divya, Rani, V. V., Manzoor, K., Menon, D., Selvamurugan, N., Nair, S. V. The design of novel nanostructures on titanium by solution chemistry for an improved osteoblast response. Nanotechnology 20, 195101 (2009).

[55] Bico, J., Thiele, U., Quere, D. Wetting of textured surfaces. Colloids Surf A Physicochem Eng Asp 206, 41-6 (2002).

[56] Ponsonnet, L. et al. Relationship between surface properties roughness, wettability of titanium and titanium alloys and cell behaviour. Mater Sci Eng C Mater Biol Appl 23, 551-60 (2003).

[57] Klinger, A., Steinberg, D., Kohavi, D., Sela, M. N. Mechanism of adsorption of human albumin to titanium in vitro. J Biomed Mater Res 36, 387-92 (1997).

[58] Kurrat, R. et al. Plasma protein adsorption on titanium: comparative in situ studies using optical waveguide lightmode spectroscopy and ellipsometry. Colloids Surf B Biointerfaces 11, 187-201 (1998).

[59] Kosmulski, M. Attempt to determine pristine points of zero charge of Nb2O5, Ta2O5, and HfO2. Langmuir 13, 6315-20 (1997).

[60] Sela, M. N., Badihi, L., Rosen, G., Steinberg, D., Kohavi, D. Adsorption of human plasma proteins to modified titanium surfaces. Clin Oral Implants Res 18, 630-8 (2007).

[61] Richert, L., Variola, F., Rosei, F., Wuest, J. D., Nanci, A. Adsorption of proteins on nanoporous Ti surfaces. Surf Sci 604, 1445-51 (2010).

[62] Yang, Y., Cavin, R., Ong, J. L. Protein adsorption on titanium surfaces and their effect on osteoblast attachment. J Biomed Mater Res A 67, 344-9 (2003).

[63] Yang, Y., Glover, R., Ong, J. L. Fibronectin adsorption on titanium surfaces and its effect on osteoblast precursor cell attachment. Colloids Surf B Biointerfaces 30, 291-7 (2003).

[64] Rivera-Chacon, D. M. et al. Fibronectin and vitronectin promote human fetal osteoblast cell attachment and proliferation on nanoporous titanium surfaces. J Biomed Nanotechnol 9, 1092-7 (2013).

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7. Figures

Fig. 1. Surface FE-SEM morphologies of test Ti and Ti2448 specimens: (a) Ti-M: Ti specimen polished with SiC paper upto #1200; (b) Ti2448-M: Ti2448 specimen polished with SiC paper upto #1200; (c) Ti2448-A1: Ti2448-M treated through electrochemical anodization with current A1; (d) Ti2448-A2: Ti2448-M treated with current A2.

(a)

(b)

(c)

(d)

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Fig. 2. Cross-sectional TEM images of anodized Ti2448 specimens: (a) Ti2448-A1; (b) Ti2448-A2; (c) Higher magnification of (a) with selected area diffraction patterns.

(a) (b)

(c)

Ti2448

substrate Ti2448

substrate

Ti2448 substrate

oxide layer dense oxide layer

porous oxide layer oxide

layer

oxide layer

5 nm

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Fig. 3. Surface AFM topography and roughness of test Ti and Ti2448 specimens: (a) Ti-M; (b) Ti2448-M; (c) Ti2448-A1; (d) Ti2448-A2.

4000 nm

10 20

μ m

4000 nm

10 20

μ m

4000 nm

10 20

μ m

4000 nm

10 20

μ m

(a) (c)

(b) R

a

= 0.13 μm (d) R

a

= 0.13 μm

R

a

= 0.12 μm R

a

= 0.11 μm

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Fig. 4. Contact angle and surface free energy of test Ti and Ti2448 specimens.

Materials

ddH₂O (polar)

Contact angle (θ)

Diiodo-Methane (non-polar)

Contact angle (θ) Surface free energy

(mN/m)

56.5 ± 4.7 ° 64.3 ± 1.7 ° 15.9 ± 4.3 ° 11.0 ± 0.7 °

Ti-M Ti2448-M Ti2448-A1 Ti2448-A2

33.8 ± 3.2 ° 35.8 ± 4.4 ° 40.8 ± 2.7 ° 46.0 ± 1.6 °

56 51 74 74

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Fig. 5. Polarization curves of test Ti and Ti2448 specimens in different electrolytes: (a) SBP; (b) AS.

10^-11 10^-10 10^-9 10^-8 10^-7 10^-6 10^-5 10^-4

-2 -1 0 1 2

Current (A/cm2)

Voltage (V, SEC)

Ti-M.cor Ti2448-M.cor Ti2448-A1.cor Ti2448-A2.cor

Ti-M Ti2448-M Ti2448-A1 Ti2448-A2

Voltage (V, SEC)

Current (A/cm²)

SBP

10^-4 10^-5

10^-6 10^-7

10^-8 10^-9

10^-10 10^-11

-2 -1 0 1 2

10^-10 10^-9 10^-8 10^-7 10^-6 10^-5 10^-4

-2 -1 0 1 2

Current (A/cm2)

Voltage (V, SEC)

Ti-M Ti2448-M Ti2448-A1 Ti2448-A2

Voltage (V, SEC)

Current (A/cm²)

Ti-M Ti2448-M Ti2448-A1 Ti2448-A2

AS

10^-4 10^-5

10^-6 10^-7

10^-8 10^-9

10^-10 -2 -1 0 1 2

(b)

(a)

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Fig. 6. Protein adsorption analysis, in terms of N1s spectra, obtained using XPS of test Ti and Ti2448 specimens: (a) Albumin; (b) Fibronectin.

(a) (b)

Binding Energy (eV) Intensity of N1S

3500

2500

2000

1500 1000

500 0 3000

410 406 402 398 394 390

Ti-M Ti2448-M Ti2448-A1 Ti2448-A2

Albumin

Binding Energy (eV) Intensity of N1S

2500

2000

1500

1000

500

0

410 406 402 398 394 390

Fibronectin

Ti-M Ti2448-M Ti2448-A1 Ti2448-A2

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附件

科技部補助專題研究計畫出席國際學術會議心得報告

日期：2016 年 10 月 31 日

計畫編號 MOST 104-2221-E-040 -003

計畫名稱應用電化學陰極沉積鈣磷處理提升具超低彈性係數新型Ti-Nb-Zr-Sn鈦合金表面之骨細胞相容性質

出國人員

姓名黃何雄 (共同主持人) 服務機構及職稱國立陽明大學牙醫系/教授會議時間 2015年 8月 30日至

2015年 9月 03日會議地點波蘭、克拉科夫會議名稱 (中文) 2015年第27屆歐洲生醫材料會議

(英文) 27th European Conference on Biomaterials (ESB2015)

發表題目

(中文) 探討天然交聯劑京尼平接枝第一型膠原蛋白於鈦表面之人類骨髓間葉幹細胞反應

( 英文 ) Human Bone Marrow Mesenchymal Stem Cells Responses to Titanium Surface Coated with Type I Collagen Using Natural Cross-linker Genipin

一、參加會議經過

筆者於 2015 年 08 月底至波蘭克拉科夫參加 27th European Conference on Biomaterials (ESB 2015)，發表科技部研究成果，會議期間為2015年08月30~09月03 日。

二、與會心得

本次「2015年第27屆歐洲生醫材料會議」會場位於波蘭克拉科夫中心 (圖一)，

附近交通相當便捷，非常適合舉行國際性會議。該會議會場的設施完善，令筆者印象非常深刻。大會於08月31日舉行開幕式(圖二)。並邀請許多世界上知名的學者進行大會特邀報告，其中加拿大學者Michael V. SEFTON教授演講的”Vascularization in Tissue Engineering: Alternative Foreign Body Responses” 、波蘭學者 Małgorzata LEWANDOWSKA-SZUMIEŁ教授演講的”Cell-made or Man-made Materials for Bone Reconstruction” 及四川大學顧忠偉教授演講的 ” Bioinspired Design of Dynamic Macromolecular for Gene Delivery”(圖三)皆讓筆者大有所獲。

會議進行的同時，會場外面亦同時舉行了廠商產品展示會及貼示報告交流，此為一般國際會議中常見到的安排，其目的是增加與會者更多的交流管道。會議中也舉辦許多比賽，促進大家在研究領域中的認真與積極，讓年輕學者有許多實質的交流機會。大體而言，會場的布置及展示會的內容而言，主辦單位非常用心的投入。

筆者於09月01日參加poster session (圖四)，會場交流相當熱絡，筆者也與相關領域

學者們進行學術交流(圖五)。筆者所發表的oral報告題目為“Human Bone Marrow

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Using Natural Cross-linker Genipin”(圖六)，為科技部計畫之研究成果。

本次會議的主題眾多，包括 Bone Tissue Engineering 、 Cartilage Tissue Engineering 、 Drug Delivery 、 Surface Modification 、 Cell Instructive Materials 、 Advanced Manufacturing、Osteointegration、Neural Regeneration等數專業領域。筆者主要參加 Synthesis and Fabrication of Biomaterials and Devices 及 Interactions of Biomaterials and cells等主題的論文發表。

圖一、ESB 2015 會場外觀。

圖二、ESB 2015 大會主席於 08 月 31 日會議開幕式中致詞。

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圖三、筆者聆聽四川大學顧忠偉教授演講。

圖四、會議poster session會場一角。

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(a) (b)

圖五、筆者在會場與中國科學院金屬研究所徐堅教授 ((a)圖中) 及 (b) 四川大學顧忠偉教授((b)圖中)、浙江大學高長有教授((b)圖右)進行學術交流與合影。

圖六、筆者於 08 月 31 日進行的口頭報告。

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三、發表論文摘要

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四、建議

為了鼓勵國內生醫材料相關領域的研究及提升研發技術的水準，舉辦國際性的會議與積極參與國際性相關領域的重要會議，是達到上述目標有效的方法之一。此次第27屆歐洲生醫材料會議是全世界醫材領域學者都相當關注的學術會議，不論是活動內容或是學術交流，皆是值得參加此會議的特色。此外，科技部長期在學術研究上所付出的心力，筆者個人持非常高度的肯定。同時也感謝科技部在經費上的補助 (MOST 104-2221-E-040 -003)，讓筆者有幸能參與此重要的學術交流活動，激發出更多的研究構想。

五、攜回資料名稱及內容

筆者於會後攜回資料豐富，包括所參加的會議論文集 (包含口頭及海報論文之摘

要），以及會議材料展示會的寶貴資料（包含最新的各項生醫材料研究產品及技術資

訊），上述資料將可做為國內相關學者及業界研發新生醫材料及技術重要參考。

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附件

科技部補助專題研究計畫出席國際學術會議心得報告

日期：2016 年 10 月 31 日

計畫編號 MOST 104-2221-E-040 -003

計畫名稱應用電化學陰極沉積鈣磷處理提升具超低彈性係數新型Ti-Nb-Zr-Sn鈦合金表面之骨細胞相容性質

出國人員

姓名黃何雄服務機構及職稱國立陽明大學牙醫系/教授

會議時間 2015年 8月 30日至

2015年 9月 03日會議地點波蘭、克拉科夫會議名稱 (中文) 2015年第27屆歐洲生醫材料會議

(英文) 27th European Conference on Biomaterials (ESB2015)

發表題目

(中文) 探討天然交聯劑京尼平接枝第一型膠原蛋白於鈦表面之人類骨髓間葉幹細胞反應

( 英文 ) Human Bone Marrow Mesenchymal Stem Cells Responses to Titanium Surface Coated with Type I Collagen Using Natural Cross-linker Genipin

一、參加會議經過

筆者於 2015 年 09 月至波蘭克拉科夫參加 27th European Conference on Biomaterials (ESB 2015)，發表科技部研究成果，會議期間為2015年08月30~09月03 日。

二、與會心得

本次「2015年第27屆歐洲生醫材料會議」會場位於波蘭克拉科夫中心 (圖一)，

附近交通相當便捷，非常適合舉行國際性會議。該會議會場的設施完善，令筆者印象非常深刻。大會於08月31日舉行開幕式(圖二)。並邀請許多世界上知名的學者進行大會特邀報告，其中加拿大學者Michael V. SEFTON教授演講的”Vascularization in Tissue Engineering: Alternative Foreign Body Responses” 、波蘭學者 Małgorzata LEWANDOWSKA-SZUMIEŁ教授演講的”Cell-made or Man-made Materials for Bone Reconstruction” 及四川大學顧忠偉教授演講的 ” Bioinspired Design of Dynamic Macromolecular for Gene Delivery”(圖三)皆讓筆者大有所獲。

會議進行的同時，會場外面亦同時舉行了廠商產品展示會及貼示報告交流，此為一般國際會議中常見到的安排，其目的是增加與會者更多的交流管道。會議中也舉辦許多比賽，促進大家在研究領域中的認真與積極，讓年輕學者有許多實質的交流機會。大體而言，會場的布置及展示會的內容而言，主辦單位非常用心的投入。

筆者於09月01日參加poster session (圖四)，會場交流相當熱絡，筆者也與相關領域

學者們進行學術交流(圖五)。筆者所發表的oral報告題目為“Human Bone Marrow

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Using Natural Cross-linker Genipin”(圖六)，為科技部計畫之研究成果。

本次會議的主題眾多，包括 Bone Tissue Engineering 、 Cartilage Tissue Engineering 、 Drug Delivery 、 Surface Modification 、 Cell Instructive Materials 、 Advanced Manufacturing、Osteointegration、Neural Regeneration等數專業領域。筆者主要參加 Synthesis and Fabrication of Biomaterials and Devices 及 Interactions of Biomaterials and cells等主題的論文發表。

圖一、ESB 2015 會場外觀。

圖二、ESB 2015 大會主席於 08 月 31 日會議開幕式中致詞。

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圖三、筆者聆聽四川大學顧忠偉教授演講。

圖四、會議poster session會場一角。

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(a) (b)

圖五、筆者在會場與中國科學院金屬研究所徐堅教授 ((a)圖中) 及 (b) 四川大學顧忠偉教授((b)圖中)、浙江大學高長有教授((b)圖右)進行學術交流與合影。

圖六、筆者於 08 月 31 日進行的口頭報告。

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三、發表論文摘要

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四、建議

為了鼓勵國內生醫材料相關領域的研究及提升研發技術的水準，舉辦國際性的會議與積極參與國際性相關領域的重要會議，是達到上述目標有效的方法之一。此次第27屆歐洲生醫材料會議是全世界醫材領域學者都相當關注的學術會議，不論是活動內容或是學術交流，皆是值得參加此會議的特色。此外，科技部長期在學術研究上所付出的心力，筆者個人持非常高度的肯定。同時也感謝科技部在經費上的補助 (MOST 104-2221-E-040 -003)，讓筆者有幸能參與此重要的學術交流活動，激發出更多的研究構想。

五、攜回資料名稱及內容

筆者於會後攜回資料豐富，包括所參加的會議論文集 (包含口頭及海報論文之摘

要），以及會議材料展示會的寶貴資料（包含最新的各項生醫材料研究產品及技術資

訊），上述資料將可做為國內相關學者及業界研發新生醫材料及技術重要參考。

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科技部補助計畫衍生研發成果推廣資料表

日期:2016/11/14

科技部補助計畫

計畫名稱: 應用電化學陰極沉積鈣磷處理提升具超低彈性係數新型Ti-Nb-Zr-Sn鈦合金表面之骨細胞相容性質

計畫主持人: 李慈心

計畫編號: 104-2221-E-040-003- 學門領域: 生醫材料

無研發成果推廣資料

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104年度專題研究計畫成果彙整表

計畫主持人：李慈心計畫編號：104-2221-E-040-003-

計畫名稱：應用電化學陰極沉積鈣磷處理提升具超低彈性係數新型Ti-Nb-Zr-Sn鈦合金表面之骨細胞相容性質

成果項目量化單位

質化

（說明：各成果項目請附佐證資料或細項說明，如期刊名稱、年份、卷期、起訖頁數、證號...等）　　　　　　　

國內

學術性論文

期刊論文 0

研討會論文 0 篇

專書 0 本

專書論文 0 章

技術報告 0 篇

其他 0 篇

智慧財產權及成果

專利權發明專利申請中 0

件

已獲得 0

新型/設計專利 0

商標權 0

營業秘密 0

積體電路電路布局權 0

著作權 0

品種權 0

其他 0

技術移轉件數 0 件

收入 0 千元

國外

學術性論文

期刊論文 0

研討會論文 1 篇參加""""2015年第27屆歐洲生醫材料會

議""""，口頭發表文章一篇。

專書 0 本

專書論文 0 章

技術報告 0 篇

其他 0 篇

智慧財產權及成果

專利權發明專利申請中 0

件

已獲得 0

新型/設計專利 0

商標權 0

營業秘密 0

積體電路電路布局權 0

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品種權 0

其他 0

技術移轉件數 0 件

收入 0 千元

參與計畫人力

本國籍

大專生 0

人次

碩士生 0

博士生 1 不支薪兼任研究助理

博士後研究員 0

專任助理 0

非本國籍

大專生 0

碩士生 0

博士生 0

博士後研究員 0

專任助理 0

其他成果

（無法以量化表達之成果如辦理學術活動

、獲得獎項、重要國際合作、研究成果國際影響力及其他協助產業技術發展之具體效益事項等，請以文字敘述填列。）　　

科技部補助專題研究計畫成果報告 期末報告