Piezoelectric materials for bone repair application : differentiation mechanisms and approaches

The process of bone repair and regeneration requires multiple physiological cues including biochemical, electrical and mechanical - that act together to ensure functional recovery. Electrical stimulation/electrical microenvironment are known effect the process of bone regeneration by altering the cellular response and are crucial in maintaining tissue functionality. Myriad materials have been explored as bioactive scaffolds to deliver these cues locally to the damage site, amongst these piezoelectric materials have demonstrated significant potential for tissue engineering and regeneration, especially for bone repair. Piezoelectric materials, owing to their capability of generating charges/potentials in response to mechanical deformations, have displayed great potential for fabricating smart stimulatory scaffolds for bone tissue engineering. They have the ability to deform with physiological movements and consequently deliver electrical stimulation to cells or damaged tissue without the need of an external power source. Bone itself is piezoelectric and the charges/potentials it generates in response to mechanical activity are capable of enhancing bone growth. Piezoelectric materials are capable of stimulating the physiological electrical microenvironment, and can play a vital role to stimulate regeneration and repair. In this work, piezoelectric polymer poly(vinylidene fluoride) was utilised and processed into fibres to investigate the role scaffold morphology (films or fibres) and fibre diameter on response of mouse osteoblast cells. Two different techniques of fibre fabrication, solution blow spinning and electrospinning were compared. Osteogenic differentiation (analysed using ALP activity assessment) of MC3T3-E1 cells was found to be significantly higher in cells seeded on PVDF films than on fibres. This preliminary investigation was followed by studying the mechanism of differentiation of cells on PVDF films. It was found that ERK/MAPK pathway was upregulated in cells on piezoelectric PVDF films in comparison to PVDF non-poled films. The expression of osteogenic genes Runx2 and Col1α1 was also significantly upregulated on the piezoelectric substrates. PVDF films were then stimulated using pulsed ultrasound to generate electrical signals which were recorded (~500mV) and simulated, and were found to enhance the alkaline phosphatase activity of cells under co-stimulation. The studies conducted provide useful information about osteogenic differentiation of cells by piezoelectric materials and also hint at huge potential of utilising these materials in combination with ultrasound to stimulate/enhance the process of bone repair.