The Effect of Nanomechanical Stimulation Strategies on the Shear Piezoelectric Response of Poly( <scp>l</scp> -lactide) (PLLA)

Electrical stimulation has been shown to enhance tissue regeneration, which is why piezoelectric-polymer-based scaffolds are on the rise for advanced tissue-engineering approaches. Recent studies have shown that electrical cues can modulate cell function in vitro and in vivo and that these cues can be delivered through the application of an external noninvasive ultrasound (US) source to actuate a piezoelectric polymer. However, poly(l-lactide) (PLLA) possesses a shear piezoelectric coefficient and therefore requires different strategies of US stimulation relative to other well-established piezoelectric materials such as poly(vinylidene fluoride-trifluoroethylene) P(VDF-TrFE). Thus, this work compares three different stimulation methods ranging from 1 to 500 kHz (a nanokicking bioreactor, an US transducer, and an US bath) to actuate a PLLA diaphragm with the aim of creating a bioelectrical cell culture device. The US bath stimulated PLLA films (37 kHz) generated an output voltage of 548 ± 16 mV, the highest of all tested systems. The nanokicker stimulated PLLA films (1.3 kHz) were associated with a voltage output of 4.8 ± 0.7 mV, and the US probe (500 kHz) actuated films generated an output voltage of 9.1 ± 0.8 mV, which is still high enough for electrical cell stimulation. Moreover, the influence of the film tension on the voltage output was examined, and reduced tension was observed to increase the piezoelectric response of the PLLA films by 118% and reduce the piezoelectric response of P(VDF-TrFE) films by 24%. This shows that piezoelectric PLLA-based scaffolds can be designed in a manner to take advantage of the shear piezoelectric effect of PLLA, when applying external US stimulation.