Evaluation Stability the Antibacterial Efficacy and of Strontium Incorporated Hydroxyapatite [Sr-HA] Coated Mini-screws Used for Maxillary Canine Retraction: A Randomized Clinical Trial
Phase: NA
Conditions: Gingival Inflammation and Loss the Orthodontic Mini-screws
Sponsor: Mansoura University


Mansoura University 
Faculty of Dentistry
Department of Orthodontics
“ Evaluation of the Antibacterial Efficacy and 
Stability of Strontium Incorporated 
Hydroxyapatite [Sr-HA] Coated Mini-screws 
Used for Maxillary Canine Retraction:
A Randomized Clinical Trial “
Protocol of Thesis
Submitted To the Faculty of Dentistry, Mansoura University 
in Partial Fulfilment of the Requirements for Obtaining 
Master Degree of Dental Science (Orthodontics)
Submitted By
Hind Hussein Jasim Mohammed Al-Khazraji
BDS [2012]
Faculty of Dentistry University of AlYarmouk,Iraq,Baghdad
[2025]
 Documents Date :2025/4/15

Supervisors
Dr. Ahmad Mohammed Hafez
Professor of Orthodontics Department OF Orthodontics 
Faculty OF Dentistry-Mansoura University
Dr. Nehal Fouad Albelasy
Assistant Professor of Orthodontics Department of 
Orthodontics Faculty of Dentistry, Mansoura University
Dr. Waleed Mahmoud Eldars
Professor of Medical microbiology and Immunology 
Department of Medical microbiology and Immunology 
Faculty of Medicine, Mansoura University

1
Introduction
Orthodontic mini-screws (OMS) play an important role in orthodontic 
treatment as they represent an absolute skeletal anchorage, especially in 
difficult cases that require high orthopedic forces such as expansion, 
distalization, intrusion and even with skeletally anchored fixed functional 
appliances 1. The retention of orthodontic mini screws depends mainly on two 
different mechanisms, namely, primary stability and partial osseointegration 2. 
The former depends on three main factors, which are summarized as follows:
• Mode of insertion.
• Surface texture and configuration of the orthodontic mini screw, and;
• Quality of bone 3.
On the other hand, partial oseointegration relies on direct functional and 
structural connections between the outer surface of the  mini screws and the jaw 
bone 4.    Despite the great success rate of orthodontic mini screws as absolute 
anchorage devices with different cases of malocclusion, there is about a 30% 
failure rate due to bacterial infections and soft tissue and bone inflammation 
surrounding the orthodontic mini screws . So Some problems may occur during 
the use of mini-screws, such as peri–implant mucositis, mobility, and 
postoperative pain. Moreover, with the application of heavy forces, there is a 
weak connection between bone and the surface of the mini-screw 4,5 . Finding a 
solution to the failure of orthodontic mini screw has attracted the attention of 
many researchers, and some studies reported possible solutions, including 
different modalities and techniques for the method and angle of insertion of the 
mini-screw more recently, the application of different surface coatings to 
orthodontic mini screw has been investigated 6,7.
Strontium compounds have demonstrated varying antibacterial effects 
against different bacterial strains making them suitable for enhancing the 
antimicrobial properties of medical devices. These compounds can inhibit

2
bacterial growth, impede the permeability of the cytoplasmic membrane, and 
slow the replication of bacterial chromosomes and cell metabolism 8,9. In recent 
years, Sr has been incorporated into dental and orthopedic biomaterials to 
minimize the risk of secondary caries in dental restorations 10. It has also been 
used in injectable bone cement for minimally invasive delivery of 
Antimicrobials in vertebral compression fractures, aiming to inhibit microbial 
contamination and prevent implant-related infections 11.
Furthermore, Sr- coated implants have been explored for the prevention 
of peri-implantitis 12 As The major components of the bone extracellular matrix 
(ECM) are collagen types I, III, and V, as well as hydroxyapatite (HA). HA, 
also known as calcium apatite, contains Ca minerals within the matrix. Sr is an 
important trace element found in the body and shares similar chemical 
properties and structure to Ca. As a result, Sr can actively incorporate into the 
crystal lattice of HA 13,14.
Divalent cation have captured the interest of researcher’s biomedical and 
dental fields due to their beneficial effects on bone formation. These metallic 
elements are similar to trace elements found in human bone. Strontium is 
divalent cation commonly found in various biomaterials. Since strontium has a 
radius similar to calcium, it has been used to replace calcium in any calcium- 
containing biomaterials. Strontium has the ability to inhibit bone resorption and 
increase bone deposition, making it useful in treatment of osteoporosis. 
Strontium has also been used as a radio pacifier in dentistry and has been 
incorporated into a variety of dental material to improve their radiopacity.
Furthermore, strontium has been shown to improve the antimicrobial and 
mechanical properties of dental materials promote enamel remineralization , 
alleviate dentin hypersensitivity, and enhance dentin regeneration 15.
In vitro study 16 outlines a method for coating temporary orthodontic 
titanium mini-screws with two biocompatible nanoparticles, silver/ 
hydroxyapatite (Ag/HA) and zinc oxide nanoparticles (ZnO NPs), with the aim

3
of reducing inflammation around the mini- screws. Among the two coatings, 
ZnO NPs demonstrated superior antimicrobial activity, better cytocompatibility, 
and lower cytotoxicity on all tested cell types, including oral epithelium, bone 
cells, and fibroblasts, compared to the Ag/HA NPs coating.
In another study 17,fluorohydroxyapatite(FHA)and fluorohydroxyapatite/ 
strontium (FHA–Sr) coatings were synthesized using the sol–gel method and 
applied to Ti6Al4V alloys via dip coating. Anodization by the MAA process 
and subsequent hydrothermal treatment improved coating morphology, creating 
dense, sphere-like particles with the addition of Sr2+ ions .Strontium doping 
enhanced crystallinity, shifted peaks to lower angles, and increased peak 
intensities due to its higher atomic weight compared to calcium. The FHA–Sr 
coatings exhibited higher shear bond strength (43 MPa) compared to FHA 
coatings (38 MPa), attributed to compact morphology, covalent bonding, and 
better diffusion at the coating-Ti interface MTT tests confirmed non-toxicity of 
both coatings to MG63 cells, with consistent cell viability over 3 and 7 days. 
Cell adhesion studies showed more elongated pseudopodia on FHA–Sr 
surfaces, indicating enhanced osteoblast interaction. ALP activity on FHA– Sr 
samples significantly increased by 105% over 14 days, compared to a 43.28% 
increase in FHA samples , suggestion that Sr2+ ions enhance bone 
mineralization and support osteoblast proliferation and differentiation by 
interacting with calcium-sensing receptors.
Also another study18 found that Titanium implants capable of releasing 
strontium and silver ions demonstrated outstanding in vivo bone- bonding 
properties and effective antimicrobial activity against MSSA both in vitro and 
in subcutaneous pockets in vivo. These results highlight the potential of this 
novel material as a promising solution to address challenges related to bone 
fragility and surgical site infections (SSI).

4
There are several studies 19,20,21 discussing the coating of orthodontic 
mini-screws, including The modification of orthodontic mini-screw surfaces 
plays a crucial role in enhancing both their stability and antibacterial properties, 
the bioactive Ti-6Al-4V mini-screws demonstrated improved osseointegration 
and mechanical retention, particularly when coated with Ca-P via cyclic pre- 
calcification after TiO2 nanotube formation , this surface treatment accelerated 
bone integration and enhanced stability19. Similarly, the incorporation of 
antibacterial agents, such as Ti-BP-AgNP and Ti-BP-SeNP, provided strong 
antimicrobial effects, with SeNP offering a promising alternative due to its 
lower cytotoxicity20. Additionally, coating orthodontic micro-implants with 
TiO2 and ZnO NPs proved effective in preventing biofilm formation, reducing 
microbial infections, and minimizing peri-implant inflammation. Collectively, 
these findings emphasize the importance of surface modifications in improving 
the performance, stability, and antibacterial properties of orthodontic implants .

5
Aim of study
The aim of this study is to evaluate the antibacterial efficacy and stability 
of strontium- incorporated hydroxyapatite (Sr-HA) coated orthodontic mini- 
screws used in maxillary canine retraction in comparison to uncoated mini- 
screws.

6
Material and Method
Study Design:
This is a double-blind, split-mouth, randomized controlled clinical study 
with a 1:1 right-to-left allocation. The clinical study aimed at comparing the 
effects of Strontium hydroxyapatite coating and uncoating the orthodontics 
mini-screws and assessment the stability, antimicrobials in addition 
measurement gingival blood flow. The study will include (40) mini-screws, 
divided equally into two groups: one group without coating by Strontium 
Incorporated Hydroxyapatite and the other coating by Strontium Incorporated 
Hydroxyapatite .
Sample Size:
A total sample size (20) patients will be included in this study and (40) mini- 
screws, divided equally in to two groups:
• Group 1 [Control]: (20) uncoated orthodontic  mini screws .
• Group 2 : (20) coated orthodontic mini screws .
Inclusion Criteria
• Adult patients within an age range (16-20) years.
• Orthodontic	 treatment	 plan	 requiring	 the	 extraction	 of	 the	 upper 
first premolars.
• Patients have fully permanent teeth are erupted (third molars are not 
included).
• No previous orthodontic treatment.

7
• No medical problem that could interfere with treatment.
Exclusion Criteria
• Presence of problematic healing such as, compromised immune defense, 
bleeding disorder, pathological bone quality, and xerostomia.
• Inadequate oral hygiene.
• Heavy smoking.
Ethical Consideration:
All selected patients will be informed about the aims and characteristics 
of the study, the potential risks and benefits and the Option of withdrawing 
from it whenever they desire. Then all patients will sign the informed consent 
document. All patients will be informed about the results after finishing. All 
selected patients' personal data and details will be held and handled 
confidentially and privately in the orthodontic department, faculty of dentistry, 
Mansoura University, the study will follow the guidelines of the ethical 
committee of Faculty of dentistry,Mansoura University.
Methods:
•
All patients will be treatment with fixed appliance and Roth type brackets 
where leveling and alignment will be done utilizing nickel titanium.
•
Extraction the upper first premolars and retraction the canine will be done 
using 17 ×25 SS wire.
•
A periapical X-ray will be taken to confirm the orthodontic miniscrew 
position to avoid interference with adjacent root and to ensure that there 
are no periapical lesion.

8
•
Symmetrical orthodontic mini screws will be inserted between the second 
premolar and first molar.
• The orthodontic mini screws that will be used in this study will be self-
drilling, conical in shape, 1.6 mm in diameter, and 8 mm in length, 
constructed of titanium alloy, i well be purchased from Dentaurum 
company [Germany].
• The orthodontic mini screws  were loaded with a 150 g NiTi coil spring.
• On one side, a coated will be inserted, and on the other side, an 
uncoated orthodontic mini screws will be used for the same patient.
•
Coated	
materials	
will	
utilize	
Strontium  
incorporated Hydroxyapatite applied by electrochemical 
deposition and concentration percentage
about 5 % .
• No mucoperiosteal flap will be raised, and no pilot hole will be made 
during the procedure.
• Will be assessed throughout follow-up periods of up to four months.
Outcome Measurement:
Assessment Orthodontic mini-screws stability (coated and uncoated) 
using Periotest device , Evaluate antimicrobial effect of Strontium incorporated 
Hydroxyapatite using Enzyme -Linked Immunosorbent Assay technique  ,  and 
Evaluate the gingival health and blood flow .

9
Statistical analysis
Data will be analyzed using SPSS (statistical package for social sciences) 
version 26. Qualitative data will be presented as number and percent, 
Quantitative data will be tested for normality by Kolmogrov-Smironv test then 
described as mean and standard deviation for normally distributed data and 
median and range for non-normally distributed. The appropriate statistical test 
will be applied according to data type with the following suggested tests: Chi- 
Square for categorical variable Student T test, Mann Whitney U test and 
Spearman correlation is used to assess correlation between continuous 
variables.
Duration of the study:
• This study is suggested to be finished in one year.
Cost:
• 150,000 Egyptian pounds.

10
References
1.
Venugopal A, Muthuchamy N, Tejani H, Gopalan A-I, Lee K-P, Lee H-J, 
et al. Incor- poration of silver nanoparticles on the surface of orthodontic 
microimplants to achieve anti- microbial properties. Korean J Orthod 
2017;47:3–10. http:// dx.doi.org/10.4041/ kjod.2017.47.1.3.
2.
Hammad SM, El-Wassefy NA, Shamaa MS, Fathy A. Evaluation of zinc- 
oxide nanocoating on the characteristics and antibacterial beha- vior of 
nickel-titanium alloy. Dental Press J Orthod 2020 ; 25 : 51 – 8 . http:// 
dx.doi.org/ 10.1590/2177-6709.25.4.051-058.oar.
3.
Redžepagi c-Vražalica L, Meši c E, Pervan N, Hadžiabdi c V, Deli c M, 
Glušac M. Impact of implant design and bone properties on the primary 
stability of orthodontic mini-implants. Appl Sci 2021;11. http:// 
dx.doi.org/ 10.3390/ app11031183.
4.
Zhou WY, Rabie ABM, Wong RWK, Tang B. Nanocoating of 
montmorillonite/Mg- b-trical- cium phosphate on orthodontic titanium 
min- iscrews 2010 3rd Int. Nanoelectron Conf 2010;817–8. http:// 
dx.doi.org/10.1109/ INEC.2010.5425193.
5.
Smeets R, Stadlinger B, Schwarz F, Beck- Broichsitter B, Jung O, Precht 
C, et al. Impact of dental implant surface modifications on 
osseointegration. Biomed Res Int 2016;2016:6285620. http://dx.doi.org/ 
10.1155/2016/6285620.
6.
Syed SS, Kulkarni D, Todkar R, Bagul RS, Parekh K, Bhujbal N. A novel 
method of coating orthodontic archwires with nanopar- ticles. J Int Oral 
Heal JIOH 2015;7:30–3.

11
7.
Zhang Y, Gulati K, Li Z, Di P, Liu Y. Dental Implant Nano-Engineering: 
Advances, Limita- tions and Future Directions. Nanomater. Nanomater 
(Basel Switzerland) 2021;11:2489. http://dx.doi.org/10.3390/ 
nano11102489.
8.
Alkhraisat, M.H.; Rueda, C.; Cabrejos-Azama, J.; Lucas-Aparicio, J.; 
Mariño, F.T.; García-Denche, J.T.; Jerez, L.B.; Gbureck, U.; Cabarcos,
E.L. Loading and release of doxycycline hyclate from strontium- 
substituted calcium phosphate cement. Acta Biomater. 2010, 6, 1522–
1528. [CrossRef] [PubMed]
9.
Guida, A.; Towler, M.; Wall, J.; Hill, R.; Eramo, S. Preliminary work on 
the antibacterial effect of strontium in glass ionomer cements. J. Mater. 
Sci. Lett. 2003, 22, 1401–1403. [CrossRef]
10.
Jayasree, R.; Kumar, T.; Mahalaxmi, S.; Abburi, S.; Rubaiya, Y.; Doble,
M. Dentin remineralizing ability and enhanced antibacterial activity of 
strontium and hydroxyl ion co-releasing radiopaque hydroxyapatite 
cement. J. Mater. Sci. Mater. Med. 2017, 28, 95. [CrossRef] [PubMed]
11.
Brauer, D.S.; Karpukhina, N.; Kedia, G.; Bhat, A.; Law, R.V.; Radecka, 
I.; Hill, R.G. Bactericidal strontium-releasing injectable bone cements 
based on bioactive glasses. J. R. Soc. Interface 2013, 10, 20120647. 
[CrossRef] [PubMed]
12.
Alshammari, H.; Neilands, J.; Svensäter, G.; Stavropoulos, A. 
Antimicrobial potential of strontium hydroxide on bacteria associated 
with peri-implantitis. Antibiotics 2021, 10, 150. [CrossRef]
13.
Wang, L.; Pathak, J.L.; Liang, D.; Zhong, N.; Guan, H.; Wan, M.; Miao, 
G.; Li, Z.; Ge, L. Fabrication and characterization of strontium-

12
14.
hydroxyapatite/silk fibroin biocomposite nanospheres for bone-tissue 
engineering applications. Int. J. Biol. Macromol. 2020, 142, 366–375.
15.
Jiang, S.; Wang, X.; Ma, Y.; Zhou, Y.; Liu, L.; Yu, F.; Fang, B.; Lin, K.; 
Xia, L.; Cai, M. Synergistic Effect of Micro-Nano-Hybrid Surfaces and 
Sr Doping on the Osteogenic and Angiogenic Capacity of Hydroxyapatite 
Bioceramics Scaffolds. Int. J. Nanomed. 2022, 17, 783. [CrossRef]
15.
Abdalla, M.M.; Sayed, O.; Lung, C.Y.K.; Rajasekar, V.; Yiu,
C.K. .Applications of Bioactive Strontium Compounds in Dentistry. J. 
Funct Biomater. 2024, 15, 216. https://
16.
Fathy Abo-Elmahasen MM, Abo Dena AS, Zhran M, Albohy SAH. Do 
silver/ hydroxyapatite and zinc oxide nano-coatings improve 
inflammation around titanium orthodontic mini-screws? In vitro study. 
Int Orthod. 2023 Mar;21(1):100711. doi:.10.1016/j.ortho.2022.100711. 
Epub 2022 Dec 1. PMID: 36463787
17.
Moloodi A, Toraby H, Kahrobaee S, Razavi MK, Salehi A. Evaluation of 
fluorohydroxyapatite/strontium coating on titanium implants fabricated 
by hydrothermal treatment. Prog Biomater. 2021 Sep;10(3):185-194. doi: 
10.1007/s40204-021-00162-7..Epub 2021 Aug 9. PMID: 34370267; 
PMCID: PMC8511198
18.
Masamoto K, Fujibayashi S, Yamaguchi S, Otsuki B, Okuzu Y, Kawata T, 
Goto K, Shimizu T, Shimizu Y, Kawai T, Hayashi M, Morizane K, 
Imamura M, Ikeda N, Takaoka Y, Matsuda S. Bioactivity and 
antibacterial activity of strontium and silver ion releasing titanium. J 
Biomed Mater Res B Appl Biomater. 2021 Feb;109(2):238-245.doi: 
10.1002/jbm.b.34695. Epub 2020 Aug 6. PMID: 32767436.

13
19.
Byeon SM, Kim HJ, Lee MH, Bae TS. Enhancement of bioactivity and 
osseointegration in Ti-6Al-4V orthodontic mini-screws coated with 
calcium phosphate on the TiO2 nanotube layer. Korean J Orthod. 2022 
Nov 25;52(6):412-419. doi: 10.4041/kjod22.118. Epub 2022 Aug 23. 
PMID: 36424809; PMCID: PMC9701629.
20.
Subramanian, S. K., Anbarasu, P., Navin, N., & Iyer, S. R. (2022). 
Comparison of antimicrobial effect of selenium nanoparticles and silver 
nanoparticles coated orthodontic mini-implants – An in vitro study. 
APOS Trends in Orthodontics, 12(1), 20–26. https://dx.doi.org/10.25259/ 
APOS_99_2021.
21.
Othman SS, El-Waseif AA, Hameed MA, Abbas QA. Antimicrobial 
behavior of nanocoated orthodontic micro-implants: An in vitro study. J 
Orthod Sci. 2024 Feb 16;13:2. doi: 10.4103/jos.jos_115_23. PMID: 
38516118; PMCID: PMC10953694.