Exploring the Formation Kinetics of Octacalcium Phosphate from Alpha-Tricalcium Phosphate: Synthesis Scale-Up, Determination of Transient Phases, Their Morphology and Biocompatibility

Even with decades of research studies behind octacalcium phosphate (OCP), determination of OCP phase formation has proved to be a cumbersome challenge. Even though obtaining a large quantity of OCP is important for potential clinical uses, it still remains a hindrance to obtain high yields of pure O...

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Main Authors: Ilijana Kovrlija, Ksenia Menshikh, Olivier Marsan, Christian Rey, Christèle Combes, Janis Locs, Dagnija Loca
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/13/3/462
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author Ilijana Kovrlija
Ksenia Menshikh
Olivier Marsan
Christian Rey
Christèle Combes
Janis Locs
Dagnija Loca
author_facet Ilijana Kovrlija
Ksenia Menshikh
Olivier Marsan
Christian Rey
Christèle Combes
Janis Locs
Dagnija Loca
author_sort Ilijana Kovrlija
collection DOAJ
description Even with decades of research studies behind octacalcium phosphate (OCP), determination of OCP phase formation has proved to be a cumbersome challenge. Even though obtaining a large quantity of OCP is important for potential clinical uses, it still remains a hindrance to obtain high yields of pure OCP. Taking that into consideration, the purpose of this study was to scale-up OCP synthesis for the first time and to use a multi-technique approach to follow the phase transformation pathway at multiple time points. In the present study, OCP has been synthesized from α-tricalcium phosphate (α-TCP), and subsequently scaled-up tenfold and hundredfold (100 mg → 10 g). The hydrolysis mechanism has been followed and described by using XRD and FTIR spectroscopy, as well as Raman and SEM. Gradual transformation into the OCP phase transpired through dicalcium phosphate dihydrate (brushite, DCPD, up to ~36%) as an intermediary phase. Furthermore, the obtained transitional phases and final OCP phases (across all scale-up levels) were tested with human bone marrow-derived mesenchymal stem cells (hBMSCs), in order to see how different phase mixtures affect the cell viability, and also to corroborate the safety of the scaled-up product. Twelve out of seventeen specimens showed satisfactory percentages of cell viability and confirmed the prospective use of scaled-up OCP in further in vitro studies. The present study, therefore, provides the first scale-up process of OCP synthesis, an in depth understanding of the formation pathway, and investigation of the parameters able to contribute in the OCP phase formation.
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spelling doaj.art-5705220b14a14501949089e4cc5642e82023-11-17T09:51:39ZengMDPI AGBiomolecules2218-273X2023-03-0113346210.3390/biom13030462Exploring the Formation Kinetics of Octacalcium Phosphate from Alpha-Tricalcium Phosphate: Synthesis Scale-Up, Determination of Transient Phases, Their Morphology and BiocompatibilityIlijana Kovrlija0Ksenia Menshikh1Olivier Marsan2Christian Rey3Christèle Combes4Janis Locs5Dagnija Loca6Rudolfs Cimdins Riga Biomaterials Innovation and Development Centre, Faculty of Materials Science and Applied Chemistry, Institute of General Chemical Engineering, Riga Technical University, Pulka 3, LV-1007 Riga, LatviaCenter for Translational Research on Autoimmune and Allergic Disease—CAAD, Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, ItalyCIRIMAT, Université de Toulouse, CNRS, Toulouse INP—ENSIACET, 4 Allée Emile Monso, CEDEX 4, 31030 Toulouse, FranceCIRIMAT, Université de Toulouse, CNRS, Toulouse INP—ENSIACET, 4 Allée Emile Monso, CEDEX 4, 31030 Toulouse, FranceCIRIMAT, Université de Toulouse, CNRS, Toulouse INP—ENSIACET, 4 Allée Emile Monso, CEDEX 4, 31030 Toulouse, FranceRudolfs Cimdins Riga Biomaterials Innovation and Development Centre, Faculty of Materials Science and Applied Chemistry, Institute of General Chemical Engineering, Riga Technical University, Pulka 3, LV-1007 Riga, LatviaRudolfs Cimdins Riga Biomaterials Innovation and Development Centre, Faculty of Materials Science and Applied Chemistry, Institute of General Chemical Engineering, Riga Technical University, Pulka 3, LV-1007 Riga, LatviaEven with decades of research studies behind octacalcium phosphate (OCP), determination of OCP phase formation has proved to be a cumbersome challenge. Even though obtaining a large quantity of OCP is important for potential clinical uses, it still remains a hindrance to obtain high yields of pure OCP. Taking that into consideration, the purpose of this study was to scale-up OCP synthesis for the first time and to use a multi-technique approach to follow the phase transformation pathway at multiple time points. In the present study, OCP has been synthesized from α-tricalcium phosphate (α-TCP), and subsequently scaled-up tenfold and hundredfold (100 mg → 10 g). The hydrolysis mechanism has been followed and described by using XRD and FTIR spectroscopy, as well as Raman and SEM. Gradual transformation into the OCP phase transpired through dicalcium phosphate dihydrate (brushite, DCPD, up to ~36%) as an intermediary phase. Furthermore, the obtained transitional phases and final OCP phases (across all scale-up levels) were tested with human bone marrow-derived mesenchymal stem cells (hBMSCs), in order to see how different phase mixtures affect the cell viability, and also to corroborate the safety of the scaled-up product. Twelve out of seventeen specimens showed satisfactory percentages of cell viability and confirmed the prospective use of scaled-up OCP in further in vitro studies. The present study, therefore, provides the first scale-up process of OCP synthesis, an in depth understanding of the formation pathway, and investigation of the parameters able to contribute in the OCP phase formation.https://www.mdpi.com/2218-273X/13/3/462octacalcium phosphateα-TCPDCPDcalcium phosphatehydrolysisscale-up
spellingShingle Ilijana Kovrlija
Ksenia Menshikh
Olivier Marsan
Christian Rey
Christèle Combes
Janis Locs
Dagnija Loca
Exploring the Formation Kinetics of Octacalcium Phosphate from Alpha-Tricalcium Phosphate: Synthesis Scale-Up, Determination of Transient Phases, Their Morphology and Biocompatibility
Biomolecules
octacalcium phosphate
α-TCP
DCPD
calcium phosphate
hydrolysis
scale-up
title Exploring the Formation Kinetics of Octacalcium Phosphate from Alpha-Tricalcium Phosphate: Synthesis Scale-Up, Determination of Transient Phases, Their Morphology and Biocompatibility
title_full Exploring the Formation Kinetics of Octacalcium Phosphate from Alpha-Tricalcium Phosphate: Synthesis Scale-Up, Determination of Transient Phases, Their Morphology and Biocompatibility
title_fullStr Exploring the Formation Kinetics of Octacalcium Phosphate from Alpha-Tricalcium Phosphate: Synthesis Scale-Up, Determination of Transient Phases, Their Morphology and Biocompatibility
title_full_unstemmed Exploring the Formation Kinetics of Octacalcium Phosphate from Alpha-Tricalcium Phosphate: Synthesis Scale-Up, Determination of Transient Phases, Their Morphology and Biocompatibility
title_short Exploring the Formation Kinetics of Octacalcium Phosphate from Alpha-Tricalcium Phosphate: Synthesis Scale-Up, Determination of Transient Phases, Their Morphology and Biocompatibility
title_sort exploring the formation kinetics of octacalcium phosphate from alpha tricalcium phosphate synthesis scale up determination of transient phases their morphology and biocompatibility
topic octacalcium phosphate
α-TCP
DCPD
calcium phosphate
hydrolysis
scale-up
url https://www.mdpi.com/2218-273X/13/3/462
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