DS0413 - Technologies pour la santé

Architectured substituted phosphate calcium coatings for bioactive bone implants – ArchiCaP

Architectured substituted calcium phosphate coatings for bioactive bone implants

Since the first hydroxyapatite coated HIPs were implanted in the mid-1980s, the clinical use of such implants has aroused many interests over the last decades. The current concern is to provide the clinicians with bioactive, antibacterial, mechanically stable coatings and to process them on any type of substrate whatever its composition or shape with a high degree of accuracy.

Joint development of two spraying processes (rf-SPS and CS) and new calcium phosphate coatings with antibacterial capacities

The project objective is to develop coatings based on multisubstituted nanostructured calcium phosphates with an adjusted morphology, excellent short and long terms biocompatibility, very good adhesion on prosthetic materials and bactericidal properties. The project therefore aims at : i) assessing the potential of two new thermal spray processes (suspension plasma spray and cold spray) to develop these «smart« calcium phosphates phases as coatings; ii) adapting the methods to treat implants of various sizes, of complex shapes, and made of metallic materials, polymeric or ceramic; iii) describing the physical, chemical and structural effects of coatings on osteoinductive properties; iv) developing new experimental and numerical approaches to determine the mechanical properties (adhesion and cohesion).

To achieve the objectives previously described, knowledge and know-how in materials and mechanical sciences, biology related to bone tissues, thermal spray technologies, and process development are required.
• WP 1 / Coatings, products & processes developments
This work package aims at: i) delivering a nanostructured substituted apatite coating mimicking the chemistry and grain size of the non-organic part of the natural bone optimized for its mechanical and biological performances; ii) evaluating the economic interest of the explored processes; iii) assessing their ability to treat parts with various sizes and shapes.
• WP 2 / Physical & mechanical characterizations
This work package aims at describing the surfaces and interfaces (physical and chemical characteristics) and at establishing the mechanical characteristics. To perform the quality assessment of the calcium phosphate coatings, the following physical and mechanical characteristics will be studied: roughness/texture, surface charge/energy, adhesion/cohesion strength, and residual stress. Dedicated experimental and numerical mechanical developments are under development.
• WP 3 / In vitro & in vivo biological characterizations
This work package aims at establishing the biological behavior (including the adhesion, proliferation and differentiation of MSCs, antibacterial activity, and in-vivo tests) of the coated implants with non-substituted and substituted calcium phosphates, and at elucidating some effects of the physical, chemical and structural characteristics of substituted calcium phosphates on the osteoinductive properties.
To find out the relationship between these 3 topics is the key point of our method.

The first phase of M. Chambard's thesis allowed choosing three protocols of synthesis of calcium phosphates. The main parameters that distinguish these syntheses are: pH, synthesis temperature, rate of addition of reagents and maturation time. The washing, drying and dispersion stages also determine the rheological characteristics of the suspensions. Thus, the powders synthesized are hydroxyapatite, either stoichiometric or biomimetic, deficient in calcium and carbonated. The Ca / P ratio is less than 1.5 for two of the powders and 1.66 for the third. The first rheological analyzes show that the three systems are shear thinning but that their state depends on the aging time. In parallel to this study, commercial reference coatings were developed by APS from two batches of different powders (sintered, crushed or agglomerated-dried) and characterized. Particular emphasis was placed on Raman spectroscopy analysis for the identification of phases (presence of ACP and oxyapatite in addition to the major hydroxyapatite) but also for phase mapping. These mappings can be carried out either on surfaces or on polished cross sections and make it possible to demonstrate the regular presence of ACP. In addition to this structural approach of the surface of the coating, a surfometric study has been initiated and also shows a difference between the two types of powder. The work of correlation of the Raman and topographic results has also been started. Mechanical and biological characterizations have begun.

The scientific and technical expected benefits of the ArchiCaP project are:
• Better understand and control the physical and chemical characteristics (composition, phase distribution, surface properties) of calcium phosphate coatings influencing the biological activity
• To improve adhesion and mechanical stability initially and in biological conditions of the coating
• To promote the adhesion, proliferation and differentiation of bone cells and correspondingly limit the proliferation of bacteria (effect of doping on these two biological activities, threshold values)
• To correlate the structural, mechanical and biological behavior in vivo
• To implement the low cost, reliable and versatile process both to treat implants with small size, complex shapes, and made of sensitive materials and to produce powders of the same materials

The technical and economic benefits of the ArchiCaP project are potentially:

In the short term (within the project duration):
To assess the industrial potential of both thermal spray processes to produce multisubstituted hydroxyapatite powders and bioactive coatings
To gain more control and more knowledge about the processes and the products
To protect and disseminate the project results
To exchange staff between the partners (especially Masters and PhD students)

In the medium term (within one year after the end of the project):
To extend the range of products and processes of the companies involved and associated
To improve production cycles and product quality
To increase the activity of partner and associated companies and even recruit staff
To create a network between French and International research groups

In the long term (within five years after the end of the project):
To be able to commercialize new products (patented or developed during the project)
To have new joined supported projects between the French and International partners

No

Because of the aging of the population, the rising incidence of diseases, the needs for replacement or repair of bone tissues are growing steadily. In France, approximately 40,000 artificial knees and 150,000 hip prostheses are implanted each year. 10% required return, causing a second surgery. In this context, the number of implants, which contributes to health expenditure in France, is increasing (5% / year). By replacing a defective joint, the aim is to help the patients to quickly recover its autonomy / mobility and in a long-lasting way. Since the first hydroxyapatite coated HIPs were implanted in the mid-1980s, the clinical use of such implants has aroused many interests over the last decades. The current concerns are the capacity of the clinicians to have bioactive, antibacterial, mechanically stable coatings and to process them on any type of substrate whatever its composition or shape with a high degree of accuracy.

The project objective is to develop coatings based on multisubstituted nanostructured calcium phosphates with an adjusted morphology, excellent short and long terms biocompatibility, very good adhesion on prosthetic materials and bactericidal properties. The project therefore aims at : i)assessing the potential of two new thermal spray processes (suspension plasma spray and cold spray) to develop these "smart" calcium phosphates as coatings; ii) adapting the methods to treat implants of various sizes, of complex shapes, and made of metallic materials, polymeric or ceramic; iii) describing the physical, chemical and structural effects of coatings on osteoinductive properties; iv)developing new experimental and numerical approaches to determine their mechanical properties (adhesion and cohesion).

The proposed PRCE project entitled ArchiCaP « Architectured substituted calcium phosphate coatings for bioactive bone implants »brings together three academic research groups and a small company – CIRIMAT of the Institut National Polytechnique de Toulouse, LGP of Ecole Nationale d’Ingénieurs de Tarbes, and BioTis of the Université de Bordeaux and 2PS, SME dedicated to plasma sprayed coatings for orthopedic implants. The multidisciplinary consortium in materials science and engineering, biology and industrial systems will also rely on CRIOAC-GSO as well as on two international groups from Universities of Sherbrooke and Barcelona that are very well-known in the thermal spray field.

Project coordination

Ghislaine BERTRAND (Centre Interuniversitaire de Recherche et d'Ingénierie des Matériaux)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

UdeS Université de Sherbrooke
PROJECTION PLASMA SYSTEME
INSERM Institut National de la Santé et de la Recherche Médicale
LGP Laboratoire Génie de Production
CIRIMAT Centre Interuniversitaire de Recherche et d'Ingénierie des Matériaux

Help of the ANR 615,983 euros
Beginning and duration of the scientific project: December 2015 - 42 Months

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