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Calcium Phosphate Based Biomaterials for Bone Augmentation
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Basic (apatite-based) calcium phosphate cements (CPCs), and acidic (brushite and monetite-based) CPCs are used as bone replacement materials because of their bioactivity, mouldability and ability to harden in place. However, their application is limited by their inherent brittleness and difficulties related to their handling. The current thesis aimed to provide solutions to these limitations.

To assess the baseline, the mechanical properties of two promising experimental and two commercially available apatite and brushite cements were investigated. The two experimental CPCs exhibited significantly higher mechanical strengths than the two commercially available ones, warranting further advancement of the former towards clinical use.

The setting reaction of brushite cements was, for the first time, quantitatively studied in the first seconds and minutes, using synchrotron X-ray diffraction. The reaction was found to include a fast nucleation induction period (<9 s), nucleation (<18 s), brushite content increase and setting completion. The effect of the commonly used retardant citric acid – which usually also gives stronger brushite cements - was also evaluated, providing important information for further cement development.  

To overcome complicated usage and short shelf life of acidic CPCs, a ready-to-use acidic CPC was developed by mixing a monocalcium phosphate monohydrate (MCPM) paste and a β-tricalcium phosphate (β-TCP) paste with suitable amounts of citric acid. The CPC showed adequate shelf life, good cohesion and mechanical performance.

To mitigate against the brittle behavior of CPCs, i) poly(vinyl alcohol) fibres were used to reinforce apatite cements, significantly improving the apatite matrix’s toughness and resistance to cracking; ii) injectable, ready-to-use organic-inorganic composites with partly elastomeric compression behavior were designed based on silk fibroin hydrogels and acidic calcium phosphates, and their ability for antibiotic drug delivery was assessed. 

In summary, insights into the functional properties of currently available CPCs as well as the setting process of brushite cements were gained and several new calcium phosphate-based formulations were developed to overcome some of the drawbacks of traditional CPCs. Further studies, in particular of the biological response, are needed to verify the potential of the developed materials for future use in the clinical setting. 

 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. , p. 55
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1700
Keywords [en]
bone substitute materials, calcium phosphate cements, apatite, brushite, monetite, setting mechanism, premixed, fibre reinforcement, composite, silk fibroin, mechanical properties
National Category
Ceramics Composite Science and Engineering
Research subject
Engineering Science with specialization in Materials Science
Identifiers
URN: urn:nbn:se:uu:diva-356982ISBN: 978-91-513-0399-4 (print)OAI: oai:DiVA.org:uu-356982DiVA, id: diva2:1237768
Public defence
2018-09-28, Häggsalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2018-09-05 Created: 2018-08-10 Last updated: 2018-09-10
List of papers
1. Compressive, diametral tensile and biaxial flexural strength of cutting-edge calcium phosphate cements
Open this publication in new window or tab >>Compressive, diametral tensile and biaxial flexural strength of cutting-edge calcium phosphate cements
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2016 (English)In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 60, p. 617-627Article in journal (Refereed) Published
Abstract [en]

Calcium phosphate cements (CPCs) are widely used in bone repair. Currently there are two main types of CPCs, brushite and apatite. The aim of this project was to evaluate the mechanical properties of particularly promising experimental brushite and apatite formulations in comparison to commercially available brushite- and apatite-based cements (chronOS Inject and Norian® SRS®, respectively), and in particular evaluate the diametral tensile strength and biaxial flexural strength of these cements in both wet and dry conditions for the first time. The cements׳ porosity and their compressive, diametral tensile and biaxial flexural strength were tested in wet (or moist) and dry conditions. The surface morphology was characterized by scanning electron microscopy. Phase composition was assessed with X-ray diffraction. It was found that the novel experimental cements showed better mechanical properties than the commercially available cements, in all loading scenarios. The highest compressive strength (57.2±6.5 MPa before drying and 69.5±6.0 MPa after drying) was found for the experimental brushite cement. This cement also showed the highest wet diametral tensile strength (10.0±0.8 MPa) and wet biaxial flexural strength (30.7±1.8 MPa). It was also the cement that presented the lowest porosity (approx. 12%). The influence of water content was found to depend on cement type, with some cements showing higher mechanical properties after drying and some no difference after drying.

Keywords
Calcium phosphate cement; Brushite; Apatite; Compressive strength; Tensile strength; Flexural strength
National Category
Ceramics
Identifiers
urn:nbn:se:uu:diva-284218 (URN)10.1016/j.jmbbm.2016.03.028 (DOI)000378969100055 ()27082025 (PubMedID)
Funder
The Swedish Foundation for International Cooperation in Research and Higher Education (STINT), IG2011-2047Swedish Research Council, 621-2011-6258
Available from: 2016-04-15 Created: 2016-04-15 Last updated: 2018-08-10Bibliographically approved
2. In-situ Synchrotron X-ray Diffraction Analysis of the Setting Process of Brushite Cement: Reaction and Crystal Growth
Open this publication in new window or tab >>In-situ Synchrotron X-ray Diffraction Analysis of the Setting Process of Brushite Cement: Reaction and Crystal Growth
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2017 (English)In: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 9, no 41, p. 36392-36399Article in journal (Refereed) Published
Abstract [en]

Brushite cements are fast self-setting materials that can be used as bone substitute materials. Although tracing their fast setting process is a challenge, it is important for the understanding of the same, which in turn is important for the material’s further development and use in the clinics. In this study, the setting rate, phase formation, and crystal growth of brushite cements were quantitatively studied by in situ synchrotron powder X-ray diffraction (SXRD) on a time scale of seconds. The influence of reactant ratios and a retardant (citric acid) on the setting reaction were analyzed. To complement the in situ investigations, scanning electron microscopy was carried out for ex situ morphological evolution of crystals. The initial reaction followed a four-step process, including a fast nucleation induction period, nucleation, crystal growth, and completion of the setting. The brushite crystal size grew up to the micro scale within 1 min, and the brushite content increased linearly after the nucleation until all monocalcium phosphate monohydrate (MCPM; Ca(H2PO4)2·H2O) had dissolved within minutes, followed by a slow increase until the end of the monitoring. By adjusting the MCPM to the β-tricalcium phosphate (β-TCP, β-Ca3(PO4)2) ratio in the starting powders, the brushite/monetite ratio in the cements could be modified. In the presence of citric acid, the formation of brushite nuclei was not significantly retarded, whereas the increase in brushite content and the growth of crystal size were effectively hindered. The amount of monetite also increased by adding citric acid. This is the first time that the brushite setting process has been characterized in the first seconds and minutes of the reaction by SXRD.

Keywords
synchrotron X-ray diffraction, setting reaction process, brushite cement, crystal size, citric acid, MCPM/β-TCP ratio
National Category
Engineering and Technology Medical Materials Biomaterials Science
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-330146 (URN)10.1021/acsami.7b10159 (DOI)000413503700092 ()
Available from: 2017-09-26 Created: 2017-09-26 Last updated: 2018-08-10Bibliographically approved
3. A ready-to-use acidic calcium phosphate cement
Open this publication in new window or tab >>A ready-to-use acidic calcium phosphate cement
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Premixed calcium phosphate cements have been developed to simplify the usage of traditional calcium phosphate cements and reduce the influence of the setting reaction on the delivery process. However, difficulties in achieving a good cohesion, adequate shelf life and sufficient mechanical properties have so far impeded their use in clinical applications, especially for the more degradable acidic calcium phosphate cements.

In this study, a brushite cement was developed from a series of ready-to-use calcium phosphate pastes. The brushite cement paste was formed via mixing of a monocalcium phosphate monohydrate (MCPM) paste and a β-tricalcium phosphate (β-TCP) paste with good injectability and adequate shelf life. The MCPM paste was based on a water-immiscible liquid with two surfactants and the β-TCP paste on a sodium hylauronate aqueous solution. The effect of citric acid as a retardant was assessed. Formulations with suitable amounts of citric acid showed good cohesion and mechanical performance with potential for future clinical applications.

Keywords
Ready-to-use, acidic calcium phosphate cement, brushite, cohesion, injectability, shelf life
National Category
Ceramics
Identifiers
urn:nbn:se:uu:diva-356978 (URN)
Available from: 2018-08-09 Created: 2018-08-09 Last updated: 2018-08-10
4. The addition of poly(vinyl alcohol) fibres to apatitic calcium phosphate cement can improve its toughness
Open this publication in new window or tab >>The addition of poly(vinyl alcohol) fibres to apatitic calcium phosphate cement can improve its toughness
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Calcium phosphate cements, and in particular hydroxyapatite cements, have been widely investigated for use as bone void fillers due to their chemical similarity to bone and related osteoconductivity. However, they are brittle, which limits their use to non-load-bearing applications.

The aim of the current study was to improve the toughness of hydroxyapatite cements through fibre reinforcement. The effect of the addition of hydrophilic, poly(vinyl-alcohol) (PVA) fibres to hydroxyapatite cement was evaluated in terms of mechanical properties, including compressive strength, diametral tensile strength and toughness (work of fracture), as well as setting time, phase composition and cement morphology. The fibre reinforcement enhanced the fracture resistance of the hydroxyapatite cement, but also simultaneously reduced the compressive strength and setting time of the cements. However, cement with 5 wt% of fibres (of powder component) could be considered a good compromise, with a compressive strength of 46.5 ± 4.6 MPa (compared to 62.3 ± 12.8 MPa of that without fibres), i.e. still much greater than that of human trabecular bone (0.1-14 MPa). A significantly higher diametral tensile strength (9.2 ± 0.4 MPa) was found for this cement compared to that without fibres (7.4 ± 1.5 MPa). The work of fracture increased four times to 9.1 ± 1.5 kJ/m2 in comparison to the pristine apatite. In summary, the hydroxyapatite cements could be reinforced by suitable amounts of PVA fibres, which resulted in enhancing the material’s structural integrity and ductility, and increased the material’s resistance to cracking.

Keywords
fibre reinforcement, apatite cement, poly(vinyl alcohol), composite, compressive strength, work of fracture, diametral tensile strength, toughness
National Category
Ceramics
Identifiers
urn:nbn:se:uu:diva-356979 (URN)
Available from: 2018-08-09 Created: 2018-08-09 Last updated: 2018-08-10
5. Silk fibroin hydrogels induced and reinforced by acidic calcium phosphate – A simple way of producing injectable, bioactive and drug-loadable composites for biomedical applications
Open this publication in new window or tab >>Silk fibroin hydrogels induced and reinforced by acidic calcium phosphate – A simple way of producing injectable, bioactive and drug-loadable composites for biomedical applications
(English)Manuscript (preprint) (Other academic)
Keywords
silk fibroin, acidic calcium phosphates, composites, hydrogels, mechanical strength, drug-loadable
National Category
Ceramics Composite Science and Engineering
Identifiers
urn:nbn:se:uu:diva-356991 (URN)
Available from: 2018-08-10 Created: 2018-08-10 Last updated: 2018-08-10

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