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Innovative process for continuous production of hydroxyapatite: from fundamental aspects to enhanced product and process performance – Innov’HAP

Innov’HAP

Innovative process for continuous production of hydroxyapatite: from fundamental aspects to enhanced product and process performance

From pathologies to raw materials require to heal

Osteoarticular pathologies are, at all ages, the first cause of handicap and raise healthcare and economical concerns. Regarding hip and knee pathologies, metallic prostheses are among the most developed bone substitutes used nowadays to circumvent these handicaps. A hydroxyapatite (HAP) coating is often applied on the prosthetic devices so as to improve the quality of the bone-implant interface, at an early stage after surgery, thus allowing one to expect increased prosthesis stability over time. This consideration appears all the more crucial taking into account population ageing statistics. <br />The HAP powder characteristics used for the coating process play a key role (e.g. in terms of osteo-integration, prosthesis durability…) and a high-quality HAP powder, specially designed for the coating processing steps, is required. To this day, industrial batch processes are chiefly based on semi-empirical parameters and have not been optimized. Similarly, the physicochemical features of the obtained powders have not received specific attention. The low yield of powder production, as well as the broad particle size distribution appear as the two main limiting parameters preventing today the development of a cost-effective process leading to high-quality coating characteristics. <br />HAP powders aimed at biomedical applications have been studied for many years in research laboratories, including CIRIMAT and LGC, and SMEs (Small and Medium companies), but the production process optimization has never been thoroughly investigated. <br />Taking into account the preceding considerations, the objectives of this project are to set up and study an innovative process for the continuous production of hydroxyapatite powder.

The strategy developed in the present project is based on the association of 3 complementary multidisciplinary approaches: (i) a fundamental study of the different steps involved in the powder production process (i.e. crystallization, washing, drying and calcination), (ii) the development of adapted tools for local-scale characterization (including through the use of adequate microfluidic systems), and finally (iii) the exploitation of these data in view of the elaboration and evaluation of an efficient continuous process design.
This project, gathers two renowned academic laboratories (CIRIMAT and LGC) involved in Materials Science, Pharmaceutical Technology, and Chemical Engineering; as well as an industrial partner (Urodelia S.A.) developing activities in the field of bone-related technologies. The quality and complementary expertise of the consortium members is intended to represent one of the strengths of this project. A rather unusual project structure is proposed here in order to take advantage of the complementarity of the consortium. We chose to study simultaneously in each task the material and the process which requires a mixing of each partner’s knowledge and know-how in all the tasks. This particular organization is possible due to the geographical proximity of the partners will in particular allow us to reactively adapt the powder quality and process based on the project outputs in “live” time.

To achieve its goals, Innov’HAP was divided into 6 main Tasks (or work packages):
-Task 0: Project management and organizational aspects
-Task 1: Study of HAP precipitation
-Task 2: Size controlling processes
-Task 3: Materials characterization, and instrumentation
-Task 4: Transfer (to pilot scale, continuous process)
-Task 5: Validations of coating performances (chemical, mechanical, biological)

The project allows to determine the impact on each step of the process of the operating conditions on the agglomeration of stoichiometric hydroxyapatite (eg granulometric distribution, morphology) and on the evolution of the phases involved (ex: Calcium / Phosphate molecular ratio). According to the results obtained, the most critical step is the beginning of the synthesis. Indeed, this is when the pH variations are the most important and where the large agglomerates are formed.
In parallel to this activity, a new innovative approach has been developed. This innovative process exceeds our expectations because it presents conditions that are easily controllable (pH, ambient temperature), a stabilization of the quality of the products linked to the chemistry implemented, a consequent saving of time and a shift in continuously production is facilitated.
The intensification and subsequent scale-up (from the bench to the semi-pilot) of the production of hydroxyapatite powder were thus carried out on the innovative process that we preferred to the classical process. The powder thus obtained was used under industrial conditions for the plasma torch coating of a titanium alloy samples (thus mimicking the prostheses). Biological, mechanical and physico-chemical characterizations and tests have been successfully carried out by recognized external service providers in the field, following the ISO 13779 and ISO 10993 series standards.

The innovative process has many advantages compared to the commonly used process: improvement of the reproducibility of the synthesis, energy savings and improvement of operator safety. The pilot-scale development (1-5 tons / year) of this innovative process is still maturing and will continue beyond the Innov'Hap project in the context of know-how transfer or / and a start-up creation carried out by members of this project.
In parallel with this valorisation action, a reflection is carried out to adapt the parameters of the production processes in order to produce hydroxyapatite powders for the additive manufacturing.

- Declaration of invention (Ref: I-16-1588) giving rise to a valuation of «know-how« by Toulouse Tech Transfert (2016) inventors: P. Gras, C. Rey, N. Abi Chebel, C. Frances, M. Tourbin, F. Brouillet, D. Grossin.
- L. Fontaine, M. Tourbin, F. Brouill

Osteoarticular pathologies are, at all ages, the first cause of handicap and raise healthcare and economical concerns. Regarding hip and knee pathologies, metallic prostheses are among the most developed bone substitutes used nowadays to circumvent these handicaps. A hydroxyapatite (HAP) coating is often applied on the prosthetic devices so as to improve the quality of the bone-implant interface, at an early stage after surgery, thus allowing one to expect increased prosthesis stability over time. This consideration appears all the more crucial taking into account population ageing statistics.
The HAP powder characteristics used for the coating process play a key role (e.g. in terms of osteo-integration, prosthesis durability…) and a high-quality HAP powder, specially designed for the coating processing steps, is required. To this day, industrial batch processes are chiefly based on semi-empirical parameters and have not been optimized. Similarly, the physicochemical features of the obtained powders have not received specific attention. The low yield of powder production, as well as the broad particle size distribution appear as the two main limiting parameters preventing today the development of a cost-effective process leading to high-quality coating characteristics.
HAP powders aimed at biomedical applications have been studied for many years in research laboratories, including CIRIMAT and LGC, and SMEs (Small and Medium companies), but the production process optimization has never been thoroughly investigated.

Taking into account the preceding considerations, the objectives of this project are to set up and study an innovative process for the continuous production of hydroxyapatite powder by implementing a global and multidisciplinary approach, ranging from fundamental aspects to the search of enhanced product and process performances. The strategy that will be developed in the present project will be based on the association of 3 complementary approaches: (i) a fundamental study of the different steps involved in the powder production process (i.e. crystallization, washing, drying and calcination), (ii) the development of adapted tools for local-scale characterization (including through the use of adequate microfluidic systems), and finally (iii) the exploitation of these data in view of the elaboration and evaluation of an efficient continuous process design.
This project, foreseen with a duration of 48 months, gathers two renowned academic laboratories (CIRIMAT Carnot Institute and LGC) involved in Materials Science, Pharmaceutical Technology, and Chemical Engineering; as well as an industrial partner (Biopowders SARL) developing activities in the field of bone-related technologies. The quality and complementary expertise of the consortium members is intended to represent one of the strengths of this project; enabling, in a mid-term perspective, the creation of a local Midi-Pyrénées platform for medically-oriented powder synthesis and processing.

The geographical proximity of the partners will in particular allow us to reactively adapt the powder quality and process based on the project outputs in “live” time. Also, it will enable us to define technical tasks (work packages) involving simultaneously the HAP material and its production process.

Project coordinator

Monsieur David GROSSIN (Centre Interuniversitaire de Recherche Ingénierie Materiaux) – david.grossin@ensiacet.fr

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

CIRIMAT Centre Interuniversitaire de Recherche Ingénierie Materiaux
LGC Laboratoire de Génie Chimique
Biopowders Biopowders SARL
Urodelia Urodelia

Help of the ANR 501,000 euros
Beginning and duration of the scientific project: January 2013 - 48 Months

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