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Submicron Calcium Phosphate Spheres for Biomedical Applications: Synthesis and Use
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Calcium phosphate spheres as biomaterials have been attracting attention in recent years. Calcium phosphate occurs naturally in bone, and a hollow structure could be advantageous for drug loading and release. The combination of a calcium phosphate chemistry and a spherical-hollow structure could be an optimal strategy for specific biomaterial applications, e.g., certain dental and drug-delivery applications.

The focus of this thesis is on the synthesis, formation mechanism and applications of hollow, spherical calcium phosphate particles. First, the thesis describes two methods for the synthesis of calcium phosphate (CaP) spherical particles. The first method involves synthesis of hollow calcium phosphate spherical particles via a supersaturated buffer solution based on a previous study. It was utilised to prepare spheres for applications in drug delivery and dentistry. The second method was developed to explain the mechanism of formation of hollow calcium phosphate spheres. It aimed at revealing the particular function of magnesium in the formation of spherical particles. With the use of this modified method, it could be concluded that the only ions active in the formation of CaP spherical particles are calcium ions, phosphate ions and magnesium ions. Compared with the thermodynamics of micellisation, a new model, called three ions virtual micelle effect, was developed to explain the mechanism of the Mg function. Following this mechanism, a series of spherical particles of other compositions were explored. These spherical particles included strontium phosphate, barium phosphate, calcium fluoride, strontium fluoride and barium fluoride.

In this thesis, CaP spheres were studied for the controlled delivery of active ingredients and as active agent for tooth remineralisation. The first investigated application was to control the release of vancomycin from Poly(methyl methacrylate) (PMMA) cement via strontium-doped CaP spheres (SCPS). The results showed that incorporation of CaP spheres into PMMA could enhance antibiotic release while maintaining the mechanical strength. The second application was to control hydrogen peroxide (HP) release from two bleaching gel, in which CP-loaded CaP spheres were the active ingredient. One gel with low HP concentration was developed as an at-home bleaching gel, and one with high HP concentration was developed as an in-office bleaching gel. The results showed that CaP spheres would give a controlled release of peroxide and thus have a potential to increase the efficacy of the bleaching. The third application was to investigate the potential for an anti-sensitivity effect of the spheres, as active agents in toothpaste. We studied the tooth tubules occlusion and the remineralisation effect of CaP spheres. After 7 days of application, the open dentin tubules and surface were fully covered by a newly formed apatite layer, demonstrating the remineralisation potential of the spheres.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. , 67 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1446
Keyword [en]
calcium phosphate, spheres, dentinal hypersensitivity, drug release, tooth bleaching
National Category
Materials Engineering
Identifiers
URN: urn:nbn:se:uu:diva-305820ISBN: 978-91-554-9737-8OAI: oai:DiVA.org:uu-305820DiVA: diva2:1039981
Public defence
2016-12-14, Å4001, Lägerhyddsvägen 1, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2016-11-22 Created: 2016-10-21 Last updated: 2016-11-28
List of papers
1. A general strategy for synthesis of inorganic spheres via magnesium
Open this publication in new window or tab >>A general strategy for synthesis of inorganic spheres via magnesium
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(English)Article in journal (Refereed) Submitted
National Category
Materials Engineering
Identifiers
urn:nbn:se:uu:diva-305819 (URN)
Available from: 2016-10-25 Created: 2016-10-21 Last updated: 2016-10-25
2. Enhanced drug delivery of antibiotic-loaded acrylic bone cements using calcium phosphate spheres
Open this publication in new window or tab >>Enhanced drug delivery of antibiotic-loaded acrylic bone cements using calcium phosphate spheres
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2015 (English)In: Journal of Applied Biomaterials & Functional Materials, ISSN 2280-8000, E-ISSN 2280-8000, Vol. 13, no 3, E241-E247 p.Article in journal (Refereed) Published
Abstract [en]

Background: Local infection near an implant may pose a serious problem for patients. Antibiotic delivery from acrylic (poly(methyl methacrylate)-based) cements is commonly used to prevent and treat infections in the proximity of, e.g., hip joint implants. However, at present, the drug release properties of PMMA cements are not optimal. An initial burst followed by very slow release means that an unnecessarily large amount of antibiotic needs to be added to the cement, increasing the risk of bacterial resistance. The main purpose of this study was to enhance drug delivery from PMMA cements without influencing the mechanical properties. Methods: We incorporated strontium-doped calcium phosphate spheres (SCPS) into PMMA cement to enhance the antibiotic release and potentially improve the bone-cement integration. The release of strontium and vancomycin was investigated using inductively coupled plasma atomic emission spectroscopy and UV spectrophotometry, respectively. Results: It was found that incorporating SCPS into PMMA could enhance the antibiotic release and deliver strontium ions to the surroundings. The incorporation of SCPS also increased the radiopacity as well as the working time of the cement. The compressive strength and Young's modulus were not affected. Conclusions: Our results showed that SCPS/PMMA antibiotic-loaded cement had enhanced antibiotic release, delivered strontium ions and maintained mechanical properties, indicating that the SCPS additive could be a good alternative for controlling the drug-delivery properties of PMMA cement.

Keyword
Calcium phosphate, Drug delivery, Hollow sphere, PMMA cement
National Category
Other Engineering and Technologies
Identifiers
urn:nbn:se:uu:diva-274721 (URN)10.5301/jabfm.5000222 (DOI)000367158000007 ()26108428 (PubMedID)
Funder
Swedish Research Council, 2013-5419VINNOVA, VINNMER 2010-02073
Available from: 2016-02-01 Created: 2016-01-25 Last updated: 2016-10-25
3. A Study for Tooth Bleaching via Carbamide Peroxide Loaded Calcium Phosphate Spheres
Open this publication in new window or tab >>A Study for Tooth Bleaching via Carbamide Peroxide Loaded Calcium Phosphate Spheres
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(English)Article in journal (Refereed) Submitted
National Category
Materials Engineering
Identifiers
urn:nbn:se:uu:diva-306171 (URN)
Available from: 2016-10-25 Created: 2016-10-25 Last updated: 2016-10-25
4. A study on diffusion of hydrogen peroxide through enamel
Open this publication in new window or tab >>A study on diffusion of hydrogen peroxide through enamel
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(English)Article in journal (Refereed) Submitted
National Category
Industrial Biotechnology
Identifiers
urn:nbn:se:uu:diva-305817 (URN)
Available from: 2016-10-22 Created: 2016-10-21 Last updated: 2016-10-25
5. Bioactive spheres: the way of treating dentin hypersensitivity
Open this publication in new window or tab >>Bioactive spheres: the way of treating dentin hypersensitivity
2016 (English)In: ACS biomaterials science and engineering, ISSN 2373-9878, Vol. 2, no 5, 734-740 p.Article in journal (Refereed) Published
Abstract [en]

Sealing exposed dental tubules is the most effective and long-term way to relieve the pain induced by dental sensitivity. A bioactive hollow sphere (strontium substituted calcium phosphate) was synthesized and added in toothpaste to study its effect on dental hypersensitivity via tooth tubules occlusion and mineralization. The size of spheres is perfect for penetrating into dental tubules, reaching to 20 pm into the tubules. The exposed dental tubules were occluded by spheres and new apatite layer after 3 days brushing. The spheres attached to the surface of dentin and the mineralized surface contained two layers, a porous layer followed by a dense apatite layer. The porous layer can be dissolved in an acidic solution, but the following dense layer could be kept even after soaking in an acid solution. In conclusion, Sr-substituted calcium phosphate spheres could be a good candidate for at-home treatment of dental hypersensitivity.

Keyword
calcium phosphate, spheres, occlusion, mineralization, dental sensitivity
National Category
Medical Materials
Identifiers
urn:nbn:se:uu:diva-284233 (URN)10.1021/acsbiomaterials.5b00499 (DOI)000375893600004 ()
Funder
Swedish Research Council, 2013-5419
Available from: 2016-04-15 Created: 2016-04-15 Last updated: 2016-10-26Bibliographically approved

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