Health Sciences University of Hokkaido Academic Repository / 北海道医療大学学術リポジトリ

北海道医療大学人間基礎科学論集編集委員会

38848

北海道医療大学学術リポジトリ
表紙
著者 北海道医療大学人間基礎科学論集編集委員会
雑誌名 北海道医療大学人間基礎科学論集
号 48
発行年 2022-11-30
URL http://id.nii.ac.jp/1145/00065127/
ISSN　１３４６ -３０２０
北海道医療大学
第　48　号
令和四年
北 海 道 医 療 大 学
人間基礎科学論集
原　著
A Comparison of Healthcare Students’ Views Regarding Workspace Communications in a Second 
Language
… ……………………………………………………………………… Shaun HOGGARD…Ａ　 1
総　説
多職種連携教育の教育効果測定と評価尺度に関する現状
－学部学生向け多職種連携学習評価尺度開発の背景－
… ……………………………………………………………………………安部　博史…Ａ　１４
表紙.indd   1 2023/02/13   11:01:18


Japanese

表紙

北海道医療大学歯学会

38874

北海道医療大学学術リポジトリ
CONTENTS
著者 北海道医療大学歯学会
雑誌名 北海道医療大学歯学雑誌
巻 41
号 2
発行年 2022-12-31
URL http://id.nii.ac.jp/1145/00065148/
The Dental Journal of Health Sciences University of Hokkaido
VOL．41，NO．2，DECEMBER，2022
CONTENTS
ORIGINAL
1 The effect of hops on oral and gut microbiota in NAFLD model mice
Tetsuro MORIKAWA, Norihiro NAKAMOTO, Nodoka SUGIYAMA, Daichi HIRAKI,
Fumiya HARADA, Osamu UEHARA, Yasushi FURUICHI, Yoshihiro ABIKO ………………………………（59）
MINI REVIEW
13 Interaction between osteoclasts and cancer cells in bone destruction of malignant tumors
Mari Shimatani, Akihiko Tanimura, Tsuyoshi Shimo ……………………………………………………………（71）
23 The regeneration of enamel : a review of the literature.
Bolortsetseg Dembereldorj, Hiroyuki Sugaya, Syed Taufiqul Islam, Taisei Kato, Akihiro Ichimura,
Yoshihito Kurashige, Koki Yoshida, Yoshihiro Abiko, Masato Saitoh …………………………………………（81）
31 Effect of psychological stress on aging and its implication on the oral cavity : A mini−review
Dedy ARIWANSA, Durga PAUDEL, Tetsuro MORIKAWA, Jun SATO, Koki YOSHIDA, Osamu UEHARA,
Hirofumi MATSUOKA, Shuhei TAKAHASHI, Hiroko MIURA, Yoshihiro ABIKO …………………………（89）
DENTAL INFORMATION
39 Recent topics……………………………………………………………………………………………………………（97）
】Ｓｅｒｖｅｒ／歯学雑誌／第４１巻２号　　　４Ｃ１５０　１Ｃ１３３／目次　ＯＴＦ／目次（英文）  2023.02.24 14.27.37  Page 2 


Bolortsetseg, Dembereldorj

38897

菅谷, 裕行

38898

Syed Taufiqul, Islam

38899

加藤, 大生

38900

市村, 彰啓

38901

倉重, 圭史

38902

吉田, 光希

38903

安彦, 善裕

38904

齊藤, 正人

38905

The regeneration of enamel : a review of the literature.

北海道医療大学博士（歯学）令和3年度thesi

ZUNIGA, HEREDIA ENRIQUE EZRA

38665

北海道医療大学学術リポジトリ
Bioactive glass surface functionalization to
develop enamel remineralization materials
著者 ZUNIGA HEREDIA ENRIQUE EZRA
学位名 博士（歯学）
学位授与機関 北海道医療大学
学位授与年度 令和3年度
学位授与番号 30110甲第368号 
URL http://id.nii.ac.jp/1145/00065050/
Abstract 
 
 
Bioactive glass surface functionalization to develop enamel 
remineralization materials 
 
 
 
 
 
 
 
 
 
2022 
Graduate School of Dentistry, 
Health Sciences University of Hokkaido 
 
Enrique Ezra ZUÑIGA HEREDIA 
 
 
 i 
Introduction 
White spot lesions, the most frequent iatrogenic effect of fixed appliance orthodontics, 
result from enamel demineralization due to an imbalance in the natural dynamic demineralization–
remineralization process. New methods to prevent and reverse this sequela of orthodontic 
treatment are based on bioactive glasses (BGs) and peptides. BGs, increase mineral saturation. 
Peptides are consider as biomimetic materials characterized to simulate the natural formation of 
hydroxyapatite prisms. 
BGs are versatile materials capable of true enamel remineralization. BG surface 
functionalization enhances bioactivity and biological interactions. The functionalization of the 
outer layer of BG opens up the possibility of developing a new material type with unique 
properties and the ability to respond to external stimuli. However, to date, surface 
functionalization of BGs has focused on the immobilization of molecules such as peptides and 
proteins, as well as controlled drug delivery. 
Biomimetic materials, such as peptides, continue to attract attention due to their size and 
easy synthesis. Peptide functionality, according to the therapeutic need, can be customized in 
terms of the chain length, amino acid type involved, and associated sequence. For example, some 
peptides cannot fold. Biomimetic materials, such as foldamers, can mimic the structural behavior 
of peptides and conform to various three-dimensional secondary structures, thus providing a larger 
molecular space, enhanced functionality, and increased resistance to enzymatic activity. 
Despite the wide variety of BG formations and peptides used for enamel remineralization, 
the mechanical characteristics of enamel have not been fully clarified. Thus, practical materials 
that allow for control over enamel remineralization are desirable. 
Photosensitive materials can be used to address this functionality issue as a molecular 
‘machine’, similar to the approach used in medical fields for drug delivery (which can be 
combined with therapies capable of repairing and producing hydroxyapatite at the nanometer 
scale). In dentistry, photosensitive materials are needed to prevent enamel demineralization and 
enhance the regeneration necessary to protect dental health. 
The aim of the present research was to design a new material capable of controlling the 
Ca2+ release and promoting enamel remineralization based on the surface functionalization of BGs. 
The research was divided into two major experiments, as described below.  
Experiment 1: 
 ii 
Surface modification of BG and loading of foldamers with enamel remineralization 
potential. 
Experiment 2: 
Synthesis of a photosensitive hybrid material based on bioactive glass nanoparticles 
(BGNPs) for the Ca2+ release control and enamel remineralization.  
Materials and methods. 
 A. Experiment 1:  
i. Design and synthesis of foldamers 
Dynamic foldamer design was realized using Spartan 18 software (Wavefunction Inc., 
Irvine, CA, USA), based on hybrid peptides with nitrogenous pyridine at positions 2 and 3 of the 
aromatic ring. The foldamer configuration was developed with the intention of imparting the 
ability to chelate Ca2+ ions. All foldamers were synthesized using traditional methods in solution, 
and were characterized by proton (1H) and carbon 13 (13C) nuclear magnetic resonance (NMR) 
and Fourier-transform infrared spectroscopy (FTIR), coupled with attenuated total reflection 
(ATR) measurements. 
ii.  Synthesis and characterization of mesoporous BG nanoparticles 
The quinary composition of BGNPs was synthesized using the sol-gel method described 
by Leite (2015) Tetraethyl orthosilicate (TEOS, 99.90% pure, Sigma-Aldrich) was dissolved in 60 
mL of EtOH and mixed with a solution of Calcium nitrate tetra hydrate (99%, Sigma-Aldrich), 
Sodium nitrate (99%, Nakalai tesque), and Strontium nitrate (99%, Sigma-Aldrich), the pH of the 
mixture was adjusted to 1.5 adding citric acid anhydrous (98%, Wako) and left stirring until 
mixture became transparent (around 20 min). The mixture was added drop-by-drop to a 1500 mL 
aqueous solution containing ammonium dihydrogen phosphate (99%, Nacalai Tesque). The pH 
was adjusted to 11.5 with ammonium solution (25%. Nacalai Tesque) and left stirring for 48 h, 
followed by a 24 h resting period. The precipitates were washed with deionized water until no 
smell of ammonia was present (around four times). A 200mL, 2% wv-1 aquos solution of Plutonic 
123 (Sigma-Aldrich) was added to the precipitated and left stirring for 30 min, followed by freeze 
drying for 72 h. The gel power was calcinated at 700ºC for 5 h to remove the surfactant. 
 iii 
ATR-FTIR and X-ray diffraction (XRD; Rint-2500; Rigaku, Tokyo, Japan) measurements over the 
2θ range of 10–70° were used to characterize the nanoparticles. Field emission-scanning electron 
microscopy (FE-SEM) and transmission electron microscopy (TEM) were used to determine the 
nanoparticle morphology; images were analyzed using ImageJ software (National Institutes of 
Health, Bethesda, MD, USA). 
iii. Surface functionalization and foldamer immobilization 
  Surface functionalization was performed with 3-amimopropyl triethoxysilane (ATPS). 
The BGNPs were cleaned under sonication for 5 min in acetone, and then dried at 100ºC in 
vacuum for 1 h. The BGNPs were added to the ATPS mixture and a 95%:5% EtOH:H2O solution. 
ATPS was preactivated by stirring the solution for 1 h. Stirring was then performed for 1 
additional hour. The BGNPs were then washed with EtOH and dried at 100ºC under vacuum for 1 
h. 
Immobilization of the foldamer was realized by immersing bioactive glass functionalized 
nanoparticles (BGNPsF) in a citrate phosphate buffer solution (pH: 5) with a foldamer 
concentration of 2 mg/mL, and stirring the resulting solution for 1 h. BGNPsF characterization 
was carried out using SEM, energy dispersive X-ray spectroscopy (EDS), XRD, and X-ray 
photoelectron spectroscopy (XPS).  
iv. Changes in Ca2+ concentration, pH, and the bioactivity of BGNPs with an immobilized 
foldamer 
The foldamer BGNP B2 was immersed in artificial saliva. The Ca2+ ion concentration and 
pH were evaluated over time with a sensor. The samples were centrifuged, and the precipitates 
were collected, washed, and dried prior to characterization by XRD, SEM, and FTIR.   
v. Enamel remineralization test 
 An enamel block (dimensions: 2 mm × 2 mm) was obtained from first premolars 
extracted for orthodontic purposes, imbibed in epoxy resin and demineralized by acid etching in 
orthophosphoric acid for 60 s. The specimens were rinsed and cleaned by sonication for 5 min in 
distilled water. The specimens were then treated in a foldamer solution (2 mg/mL) posteriorly and 
submerged in artificial saliva for 14 days. The mechanical properties of the specimens were 
assessed using a nanoindenter. 
B. Experiment 2:  
 iv 
i. Design and synthesis of the crown ether-type molecule 
Two ether ligands (L1 and L2) were conformed by an azobenzene chromophore bound to a 
chain of carbon groups with alkaloid groups. All ether ligands were synthesized in solution using 
the liquid method. 1H and 13C NMR, ATR-FTIR, and ultraviolet-visible (UV/Vis) spectroscopy 
were used for characterization. The isomerization of the heterogeneous material was evaluated by 
NMR after exposure to UV light (370 nm) and light from a blue light-emitting diode (LED; 
wavelength: 400–500 nm). 
ii. Ether ligand immobilization on bioactive glass surface and isomerization of EL1 and EL2 
immobilized on BGNPs 
Immobilization was performed in toluene under heating. The nanoparticles were dried and 
characterized by SEM, EDS, XPS, and UV/Vis spectroscopy. The new materials were names as 
EL1 and EL2.    
Isomerized EL1 and EL2 (2 mg/mL) were diluted in acetonitrile and irradiated with light 
to obtain the Trans and Cis conformations, as indicated in the UV/Vis spectra. 
iii. Changes in Ca2+ concentration, pH, and the bioactivity behavior of EL1 and EL2 
EL1 and EL2 were immersed in artificial saliva. Changes in the Ca2+ concentration and pH 
were evaluated over time using a sensor. All samples were centrifuged, and the precipitates were 
collected, washed, and dried for characterization by XRD, SEM, EDS, FTIR, and XPS.  
iv. Switch on /off 
 EL1 and EL2 were immersed in artificial saliva. The solution was constantly irradiated 
with UV (370 nm) at different times (15 min and 30 min) to subsequently be change to LED 
(400-500nm). Changes in the Ca2+ concentration and pH were evaluated over time using a sensor. 
All samples were centrifuged, and the precipitates were collected, washed, and dried for 
characterization by XRD, SEM, EDS, FTIR, and XPS. Data analysis 
v. Enamel remineralization 
 An enamel block (dimensions: 2 mm × 2 mm) was obtained from first premolars 
extracted for orthodontic purposes, imbibed in epoxy resin and demineralized by acid etching in 
orthophosphoric acid for 15 s. The specimens were rinsed and cleaned by sonication for 5 min in 
distilled water. The specimens were submerged in artificial saliva containing the different 
materials (BG, EL1 and EL2) for 7 days. The mechanical properties of the specimens were 
assessed using a nanoindenter. 
 v 
vi. Statistical analysis 
 The obtained Ca2+ concentrations and enamel mechanical properties (nano-hardness and 
elastic modulus) were analyzed by SPSS software (ver. 26.0; IBM Corp., Armonk, NY, USA) to 
identify significant differences in Ca2+ concentration. The mechanical properties of the enamel 
were assessed by one-way analysis of variance (ANOVA). 
Results and Discussion 
A. Experiment 1:  
1.  Design and synthesis of foldamers 
1H and 13C NMR spectra and FTIR measurements confirmed the structure of five 
foldamers with pyridine in different positions. 
2. Synthesis and characterization of BGNPs 
The BGNPs were analyzed by XRD, in which an amorphous phase was confirmed. The  
average particle size was 40 nm. EDS analysis was used to verify the BG composition 
(SiO2:CaO:NaO2:SrO:P2O5 = 46.1:19.3:27.0:5:2.6 mol%). 
3.  Surface functionalization and foldamer immobilization 
Nitrogen was detected in EDS and XPS analyses, confirming surface functionalization 
through the detection of nitrogen binding energy. The morphological characterization by SEM 
revealed a plate-like structure, indicating foldamer immobilization on the surface. No significant 
changes were found in the XRD spectra of BGF and BG2 materials. 
4.  Changes in Ca2+ concentration, pH, and the in-vitro bioactivity of BG 2 
Bioactivity was evaluated after immersion in artificial saliva. XRD results showed a peak 
at 32º, characteristic of an apatite-like formation. No significant changes in the BG2 or BGNP 
XRD spectra were found. 
5. Enamel remineralization test 
 Foldamer 2 had the highest nano-hardness and elastic modulus values. A statistically 
significant difference was found from the control group. Under microscopic observation, the 
sample treated by foldamer 2 showed a smoother surface. 
B. Experiment 2:  
1.  Design and synthesis of the crown ether-like molecule 
The synthesis of the two ligand types was confirmed by the NMR spectra. The 
interconversion of the ligands was verified by NMR, thus establishing the reversibility of the 
 vi 
compounds. 
2.  Ether ligand immobilization and isomerization of L1 and L2 immobilized on BGNPs 
The immobilization of L1 and L2 was confirmed by XPS, based on the nitrogen binding 
energy. The nitrogen peak intensity increased with the L concentration of the BGNPs. The new 
materials were named as EL1 and EL2. The amount of ether ligand immobilized on the surface of 
bioactive glass was 5mg, 10mg, and 30mg obtaining 6 types of materials (EL1-5, El2-5, EL1-10; 
EL2-10, EL1-30 and EL2-30).   
 The interconversion of EL1 and El2 immobilized on the BGNPs was evaluated by 
UV/Vis spectroscopy, with signals seen at 301 and 324 nm, respectively, similar to those observed 
for the heterogeneous material. No significant changes were observed in the FTIR or XRD 
measurements.  
3. In-vitro bioactivity behavior of the modified nanoparticles 
The Ca2+ concentration was lower for EL1 and EL2 than the BGNPs. XRD showed peaks 
related to the apatite layer in all samples evaluated. 
4. Switch on/off  
 The Ca2+ concentration decreased when EL1-30 and EL2-30 were irradiated with UV 
light, and increased when irradiated with blue LED light, confirming isomerization of the material 
and the capture and release of Ca2+. Thirty-minute activation provided better control over the Ca2+ 
concentration. 
5. Enamel remineralization 
 The BGNPs had higher nano-hardness and elastic modulus values. EL2 showed a 
statistically significant difference from the results obtained for the etching and control groups. 
Conclusions 
A. Experiment 1: 
The size of peptide has been described as one of the major factors to induce a proper 
enamel remineralization. In the current research the peptides were combine with foldamers to be 
able to have a ß-sheet formation but with a short chain of amino acid. 
Surface modification and foldamer immobilization did not affect the bioactivity or 
buffering capacity of the BG. 
Foldamer 2 has potential for enamel remineralization. 
B. Experiment 2: 
 vii 
 Controlling the bioactivity has gain attention in the medical area. The uses of light for 
this purpose has advantages such as reversibility, and the control of the application 
spatio-temporal. In this research the photosensitive materials were successfully synthetized and 
immobilized on the bioactive glass surface. 
EL1 and EL2 can control the availability of Ca2+, depending on its conformation. However, 
EL1 showed better enamel remineralization than EL2. 
The results of the present investigation suggest that surface functionalization of BG is 
promising for the development of BG materials. 
 
 
 


English

Bioactive glass surface functionalization to develop enamel remineralization materials

HASSAN, TUBAYESHA

38667

北海道医療大学学術リポジトリ
The effects of human dentin
phosphophoryn-derived RGD peptides on human
dental pulp stem cells in-vitro
著者 HASSAN TUBAYESHA
学位名 博士（歯学）
学位授与機関 北海道医療大学
学位授与年度 令和3年度
学位授与番号 30110甲第370号 
URL http://id.nii.ac.jp/1145/00065052/





The effects of human dentin phosphophoryn-derived RGD peptides on human dental pulp stem cells in-vitro

内海, 智恵

38677

福井, 純子

38678

Nursing Manager’s Support for Re-employment Nurses in Professional Development

石角, 鈴華

38681

介護保険施設における感染管理の現状と課題に関する文献レビュー：ドナベディアンの質評価モデルを用いた分析

西屋, 成真

38737

本谷, 亮

38738

Examination of the Effects of Self-Compassion on Shame and Guilt in Social Distress Situations

38795

北海道医療大学学術リポジトリ
投稿規程
著者 北海道医療大学歯学会
雑誌名 北海道医療大学歯学雑誌
巻 41
号 1
発行年 2022-06-30
URL http://id.nii.ac.jp/1145/00065102/
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とする．
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52
（52）
第４１巻１号　　　４Ｃ１５０　１Ｃ１３３／本文　※３１‐１から組体裁変更　ＯＴＦ／０５２～０５３　投稿規程  2022.08.03 08.46.10  Page 52 
受理証明を発行する．
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1）掲載頁は，刷り上り一人10頁程度とする．
2）カラー頁は，無料とする．
3）別刷料については，50部まで無料とし，これを超過
する場合（50部単位）には著者の実費負担とする．
11．優秀論文賞
その年の本誌に掲載された原著論文の中から「最優
秀論文賞」（1編），「優秀論文賞」（2編）を選び表彰
する．
選考は編集委員会が行う．
12．著作権の帰属
本誌に掲載された著作物の著作権は北海道医療大学
歯学会に帰属する．本会はこれら著作物の全部また
は一部を，ネットワーク媒体を含む媒体に掲載・出
版することが出来る．ただし，論文の内容について
は，著者がすべての責任を負う．
13．著者のプロフィール（6．投稿論文作成 3）参照）
巻末に著者のプロフィールを記すので，著者のスナ
ップ写真と経歴を提出すること．
14．原稿の送付および本誌に関する問い合わせ
住所：〒061－0293 北海道石狩郡当別町金沢1757番地
北海道医療大学歯学部・口腔生物学系・生理学分野
北海道医療大学歯学雑誌編集委員会（委員長 石井久淑）
Tel：0133－23－1239
e−mail：hisayosh@hoku−iryo−u.ac.jp
患者のプライバシー保護ならびに研究倫理に関する指針（2014年2月26日）
北海道医療大学歯学雑誌に掲載される症例報告等を含
む臨床研究論文では，患者のプライバシーを保護するた
め，以下の指針を遵守しなければならない．また，臨床
研究等においては，患者ならびに被験者の尊厳と人権に
配慮し，世界医師会によるヘルシンキ宣言と我が国が定
めた下記の指針ならびに法的規範を遵守しなければなら
ない．
1．患者のプライバシー保護に関する指針
1）氏名，カルテ番号，入院番号，イニシャル等，患
者個人の特定が可能となる情報は記載しない．
2）患者の住所は記載しない．ただし，疾患の発生場
所が病態等に影響する場合は，区域（県，市など）
までに限定して記載する．
3）診療日等の記載は，年月までとする．
4）診療科名と他の情報を照合することで患者が特定
され得る場合，診療科名は記載しない．
5）他施設でも診断・治療を受けている場合，その施
設名と所在地は記載しない．ただし，救急医療など
で搬送元の記載が不可欠の場合は，この限りではな
い．
6）顔写真には目隠しをする．
7）生検，剖検，画像情報などに含まれる番号等，症
例を特定できる情報は削除する．
8）以上の配慮をしても個人が特定される可能性のあ
る場合は，発表に関する同意を患者本人（または遺
族もしくは代理人，未成年者では保護者）から得
る．
9）前項の手続きが困難な場合は，筆頭著者または責
任著者（corresponding author）の所属する施設の倫
理委員会の承認を受ける．
2．遵守すべき倫理指針等＊
1）「臨床研究に関する倫理指針」（厚生労働省）（平成
20年7月31日改正）
2）「疫学研究に関する倫理指針」（文部科学省・厚生
労働省）（平成25年4月1日改正）
3）「ヒトゲノム・遺伝子解析研究に関する倫理指針」
（文部科学省・厚生労働省・経済産業省）（平成25年
2月8日改正）
4）「遺伝子治療臨床研究に関する指針」（文部科学省
・厚生労働省）（平成20年12月1日改正）
5）「ヒト幹細胞を用いる臨床研究に関する指針」（厚
生労働省）（平成25年10月1日改正）
6）「厚生労働科学研究における利益相反（Conflict of
Interest：COI）の管理に関する指針」（平成20年3月
31日厚生科学課長決定）
＊なお，上記の指針等は，管轄官庁のHPに掲示されてい
る最新版を参照すること．
53
（53）
第４１巻１号　　　４Ｃ１５０　１Ｃ１３３／本文　※３１‐１から組体裁変更　ＯＴＦ／０５２～０５３　投稿規程  2022.08.03 08.46.10  Page 53 


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