TecSan - TecSan : Technologies pour la santé et l’autonomie

Injectable bioresorbable and antibacterial composite for bone regeneration – BIOSINJECT

Submission summary

Due to the worldwide increase in life expectancy and evolution towards better life quality for patient there is an increasing demand in the development of biomaterials especially for orthopedic applications capable of: 1) injection processing using minimally invasive surgical techniques; 2) rapid and effective bone substitution, repair and even better regeneration at low cost; 3) limiting post-operative infectious risk and 4) rapid transfer to industrial scale. In a view to enhance the overall surgery benefits for the patient, four main characteristics of the biomaterial have to be considered and investigated: injectability, resorbability, biological activity (especially osteogenecity) and antibacterial activity. The strategy that will be developed in this industrial research program integrates this multiconstraints problem and it is based on the association of two innovative systems, i.e. calcium carbonate-based self-setting powders and selectively modified polysaccharides, and bioactive ions to produce an injectable composite bone substitute with biological and antibacterial activity. On one hand, the original compositions and rheological properties of injectable cement compositions entirely consisting of calcium carbonate (CaCO3) or including a high proportion of metastable CaCO3 (> 40% w/w) which have been recently demonstrated at CIRIMAT and which are expected to lead to bone cements with higher resorption rate due to CaCO3 metastability in biological fluids [Partner 1 patent]. On the other hand, new functional derivatives of chitosan and/or hyaluronic acid, leading to physical or chemical networks as a function of environment conditions have been recently synthesized at CERMAV [Partner 2 patent]. We will take advantage of these two inorganic and organic systems to propose new injectable self-setting composite formulations by controlling specific mineral-organic interactions.
The polysaccharides will have different functions: - They will be used as an adjuvant to improve paste cohesiveness while keeping the physico-chemical properties especially injectability suitable for the surgical applications.
- They will constitute the matrix of the microspheres which will be exploited to control the interconnected macroporosity of the cement on one hand, and to encapsulate biologically active agents on the other hand. Considering the drawbacks related to the widespread use of antibiotics to limit post-operative infections we propose an alternative strategy using the known antibacterial activity of silver ions. These cations can interact with tailor-made polysaccharide microspheres to give antibacterial sustained release systems within the composite. We will also investigate similar approach to impart osteogenic activity to the injectable composite through incorporation and control of the release of strontium ions whose positive effect on bone formation balance has been demonstrated. This “all-mineral ions” bioactivity strategy can also offer decisive advantage particularly regarding the costly Bone Morphogenetic Protein (BMP)-loaded biomaterials route which is currently developing. This research program implements an inter- and multidisciplinary research strategy based on the large consortium constituted which gathers 8 national partners (6 academic partners and 2 industrial partners (small companies)). It is combining highly complementary expertises of material scientists for self-setting composite material formulation, chemists to synthesize polysaccharides with tailor-made properties, rheologists for rheological characterization of composite paste, pharmacists for sustained release system formulation, microbiologists for antibacterial evaluation of the composite, biologists for cytocompatibility and biological activity in vitro evaluation of the composite, clinicians and histologists for the animal study and clinical trial, and R&D engineers for production scale-up and technology transfer.

Project coordination

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

Help of the ANR 0 euros
Beginning and duration of the scientific project: - 0 Months

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