Emergence - Emergence

Autologous white adipose tissue withdrawn extemporaneously and biphasic calcium phosphate particles for bone defect reconstruction – WHATBONE

CONFIDENTIEL Adipose tissue withdrawn extemporaneously for bone reconstruction.

This biomaterial named «WHATBONE« can be prepared extemporaneously. It is composed of calcium phosphate particles, blood or plasma, and adipose tissue. Easy to prepare, moldable, adaptable to large bone defects and cost-effective, it could be an alternative to bone autograft in human.

Bone reconstruction is a major public health concern in the world.

Bone autograft is the gold standard treatment to fill large bone defects but this method leads to frequent complications. To circumvent these side effects the strategy followed by many research groups consists in using mineral scaffolds combined with osteogenic cells obtained from bone marrow or adipose tissue after several weeks of cell culture expansion. This method will hardly become a current surgical practice, which justifies the research and development of new strategies, simpler and less expensive, which constituted a major public health issue all over the world. <br />The main objective of the WHATBONE project was to study the performance of a new biomaterial composed of adipose tissue, plasma or blood, and calcium phosphate particles (BCP) and, in case of success, to propose its industrial transfer.

This program included the following steps: 1) Find a method for the preparation of the adipose tissue, this method being applicable to a human lipoaspirate; 2) Find the best method to prepare a combination of blood or plasma, adipose tissue and BCP particles (WHATBONE composite), this method being applicable in the operating room; 3) Analyze the performance of the WHATBONE composite by implantation in long bone defect models in small and large animals; 4) In case of success, develop a kit for the preparation and the use of WHATBONE in the operating room.

RESULTS IN SMALL ANIMAL MODEL: we observed that the WHATBONE composite, composed of adipose tissue, plasma and BCP particles, after implantation in a large bone defect in rat, does not induce more bone formation than a combination of blood clot and BCP particles. RESULTS IN LARGE ANIMAL MODEL: these analysis are in progress.

Two patents protect the two biomaterials BRB and WHATBONE. The outstanding feature or this program is the licensing (2 exclusive licensing) of these two patents, leading to the industrial transfer of the biomaterial «BRB«. In case of success, we will propose to the industrial and clinical transfer of WHATBONE.

Six international patents, twenty international patents pending, two priority national patents. Signing of two agreements of exclusive licenses for the two patents WO/2010/007229 and WO/2010/007230.

The reconstruction of bone defects is one of the major challenges for orthopedic surgeons. The gold standard treatment is the bone auto graft withdrawn generally from the iliac crest. Nevertheless, this method is associated with numerous drawbacks (infection, hematomas, blood loss, chronic pain), and for some patients there may be insufficient bone. Many natural or synthetic biomaterials have been developed to avoid bone auto graft but none of them is able to reach its efficiency. Most of the cell-based methods proposed in the field of bone tissue engineering propose to associate these biomaterials with mesenchymal stem cells. These cells are withdrawn from bone marrow or from other tissues, selected, grown and differentiated during several weeks ex vivo. This approach is expensive, time consuming, difficult to transfer into clinical practice and, consequently, difficult to compare to bone auto graft.

Our general objective (GéPITOs, coordinator) has been to develop a new approach of bone tissue engineering easy to use in surgical practice (tissue withdrawn extemporaneously, no cell culture, preparation during the operating time, low cost), and having similar therapeutic properties than bone auto graft. Based on recent published data we have developed and patented (2 patents in 2008) a new type of biomaterial constituted of whole blood or white adipose tissue (WHAT) associated to calibrated biphasic calcium phosphate micro particles (BCP). We have shown that these two composites exhibit strong osteogenic properties in vivo in mice.

We have started the clinical and industrial transfer of the blood/BCP composite. This includes 1) the evaluation in bony site in dog; 2) a study of feasibility on human bodies; 3) a pilot study on fifteen patients. Implantation in dogs has provided with the proof of concept of the efficacy of this biomaterial and the first experiment on human bodies has evidenced its easy handling, malleability and adaptation to defects of various sizes. The pilot clinical study should start in the first months of 2011 as soon as we will get the legal authorizations.

The objective of the present project is to carry on the preliminary studies that we have already conducted with le WHAT and which have shown that the association of WHAT/plasma/ BCP particles is more efficient that the blood/BCP composite. Besides its scientific and clinical interests, this work is a supplementary step towards a final application. It should strengthen our patents and facilitate the industrial transfer of this technology.

The present project will be coordinated by GéPITOs and conducted with the National Veterinary School of Nantes (ENVN/ONIRIS) and the Inserm U791 (LIOAD), with the technical support of the GRAFTYS company which will supply the BCP particles used all along this program, and the FIST company for the valorization objectives. The evaluation of this new biomaterial has been planned as follows: 1) Task 1: Coordination; 2) Task 2: Optimization of the protocol setting of the biomaterial, which has to be applicable in the operating room from lipoaspirates; 3) Task 3: Evaluation in bony site in dog, which is an excellent model for bone reconstruction in human. These experiments will be conducted at the ENVN/ONIRIS following two surgical protocols already established at ENVN. The analysis of the grafted bones (scanning electron microscopy and histology) will be carried out at the histological department of the LIOAD partner, specialized in hard tissue analysis and which already collaborates with ENVN/ONIRIS and GéPITOs; 4) Task 4: Development of a commercial kit for the preparation of the biomaterial; 5) Task 5: Valorization strategy and technological transfer by the FIST company.




Project coordinator

Madame Nathalie ROCHET (CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - DELEGATION REGIONALE COTE D'AZUR) – rochet@unice.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

FIST SA France Innovation Scientifique et Transfert
L.I.O.A.D INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE - DELEGATION DE NANTES
ENVN/ONIRIS ECOLE NATIONALE VETERINAIRE AGROALIM DE NANTES (ONIRIS)
GéPITOs CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - DELEGATION REGIONALE COTE D'AZUR

Help of the ANR 268,830 euros
Beginning and duration of the scientific project: March 2011 - 24 Months

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