Design of calcium phosphate-based cement for bone regeneration and drug delivery
front of the jury composed of:
– Christèle COMBES, Pr. des Universités, INP-ENSIACET, Toulouse – Rapporteur,
– Nathalie ROCHET, Research Officer, iBV, Nice – Rapporteur,
– Xavier GARRIC, Pr. des Universités, IBMM, Montpellier – Examiner,
– Sébastien GENESTA, COO, Biologics4Life, Aix en Provence – Examiner,
– Mikhael BECHELANY, CNRS Research Director, IEM, Montpellier – Thesis Director,
– Vincent CAVAILLÈS, CNRS Research Director, IRCM, Montpellier – Co-thesis supervisor
In addition to keep the bone regeneration throughout the life, bone remodeling process makes it possible to eliminate damaged pieces of bone, repair defects and heal fractures. However, in certain critical and more comple x cases (bone pathologies, critical injuries, etc.) bone remodeling alone is not sufficient and requires the implantation of a bone substitute materials to fill the defect. In this case, autograft has long been presented as the “gold standard”, but in real ity, the quality and especially the quantity of graft available are limited. For several decades, synthetic biomaterials have taken a main role in addressing clinical iss ues. In this
context, a recent interest has been raised concerning magnesium ions, thanks to its involvement in the bone microenvironment functions.
The objective of this thesis was the study of the physicochemical and biological properties of injectable cements based on magnesium phosphate and calcium phosphates (MgCPC), in order to give solutions for clinical indications in traumatology and orthopaedics.
The first part of the thesis was dedicated to the characterization of the physicochemical properties of MgCPC cements and the influence of solid and liquid phases modifications on the final cement properties. The addition of calcium in a magnesium phosphate-based cement allowed to control the setting time, the rheology of the cement and the temperature during the setting time. The results obtained led to the creation of a satisfactory formulation from a physicochemical and biological point of view, to propose a clinical use of MgCPC for traumatological indications.
In a second part of the thesis work, prototypes of MgCPC cement combined with active principles were proposed. The physicochemical studies allowed the incorporation of two bisphosphonates (sodium alendronate and sodium risedronate) or strontium carbonate in the cement by i) direct method by mixing the compounds directly in the powder phase, ii) by indirect m ethod by encapsulating the compounds in polymer microspheres, which are then mixed in the cement. The addition of the bisphosphonate or strontium carbonate could be achieved by limiting the impacts of the cement characteristics compared to the MgCPC control cement. The results showed that in both cases, it was possible to control the release kinetics of these active ingredients to ensure continuous release over time locally at the bone site. In vitro and in vivo experiments are being finalized to demonstrate wh ich technology is the most effective for the use of MgCPC cement in orthopaedics in osteoporotic indications.