FLEXOELECTRIC SCAFFOLDS FOR BONE TISSUE ENGINEERING

"Bone is the most transplanted tissue with 1.3 million procedures every year in Europe. With an ageing demographic across Europe, bone transplant represents a significant socio-economic burden that necessitates new bone regeneration strategies in line with one of the Horizon 2020 priority: ""Smart Growth: knowledge and innovation based economy"". The field of bone tissue engineering has flourished over the last decades, owing to a solid knowledge on bone biology and increased progress on materials engineering. Recently, Prof. Gustau Catalan and his team at ICN2 have discovered that bone is flexoelectric and suggested that flexoelectric fields inside the bone structure may play a central role in bone repair and bone remodelling. Flexoelectricity is the coupling between strain gradients and polarization, whereby any dielectric can polarize in response to an inhomogeneous deformation. This project had three aims (i) provide experimental evidence of the effect of inhomogeneous deformations on bone cells, (ii) measure the flexoelectric coefficients of different medically-approved synthetic bone replacement/bone graft materials and (iii) In order to biomimic the flexoelectric character of bone, produce new synthetic bone scaffolds texture-engineered to exhibit flexoelectricity."

We have studied the effect of inhomogeneous deformations, generated by bending micro-cracked hydroxyapatite samples, on bone cells. The results confirmed that indeed strain gradients have two strong effects on bone cells: on osteocytes, they cause apoptosis and thus initiate the bone-reforming process. On osteoblasts, they stimulate osteocalcein production. The size range in which these effects was observed was consistent with a flexoelectric origin. These results have been accepted for publication.
Second, we have measured the flexoelectricity of biodegradable and/or biocompatible polymers and bioglass materials that have proven efficacy in bone repair strategies. The polymers chosen were:
- poly(L-lactic acid) (PLLA)
- polycaprolactone (PCL)
- a copolymer of PLLA and PCL: 85PLLA/15PCL
- bioglass
These polymers as stand-alone devices lack in mechanical, osteoconductive and osteogenic properties. In the view of improving their performance as devices for bone repair, nanoparticles of hydroxyapatite were incorporated (from 0 to 50 wt %) and the flexoelectric character of these composites were also determined. It is also remarkable that bioglass is flexoelectric. This, to our knowledge, is the first evidence that a glass (a non-cristalline material) can be flexoelectric. An article compiling the catalogue of flexoelectric and mechanical properties is being drafted.

The development of flexoelectricity-based applications is only starting, following important advances in our fundamental understanding of this phenomenon. In the area of biomedical engineering, it has not yet been exploited at all, as the investigation of bioflexoelectricity is in its infancy. Moreover, flexoelectricity in biocompatible materials, a crucial first step for the development of applications, had been scarcely assessed before the start of our project.
The results obtained in this action provide a bridge from the fundamental science to the applications. At the fundamental side, the measurement of the effect of fracture-generated flexoelectricity on bone cells provides a motivation for adding flexoelectricity to osteogenic therapies. At the materials side, our quantification of the flexoelectric properties of biocompatible polymers and composites (PLLA, PCL, their copolymers and composites based on PLLA, PCL and nanoparticles of hydroxyapatite, bioglass) are likely to be a very useful tool for biomedical engineers aiming to introduce flexoelectricity as a design parameter. This action has identified a few compositions of the above mentioned polymers and composites that have the ability to generate flexoelectric field theoretically large enough to stimulate cells.
One of the most interesting aspect of flexoelectricity is the possibility to design non-piezoelectric materials to exhibit piezoelectric-like properties by clever texture-engineering at the microscale. Our results show that this can be achieved using the right compositions in devices with in-built strain gradients, e.g. polymeric scaffolds with porosity gradients where the texturization generates large strain gradients. While the project has fallen short of producing an actual flexoelectric bone prosthesis, it has laid the foundations (fundamentals, materials, design parameters) for this to be achieved.

Periodic Reporting for period 1 - FLEXOBONEGRAFT (FLEXOELECTRIC SCAFFOLDS FOR BONE TISSUE ENGINEERING)

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