Synthesis and characterization of biodegradable piezoelectric nanoparticles for tissue regeneration

The non-invasive activation of piezoelectric nanomaterials via ultrasound has recently emerged as a promising approach to generate electrical charges promoting tissue regeneration. This paradigm has been investigated in different domains, including skeletal muscle tissue engineering. Inorganic piezoelectric nanomaterials have high piezoelectric coefficients, but they are not biodegradable, limiting their use in the medical context. Biocompatible and biodegradable nanomaterials are thus desirable, as they would facilitate the clinical translation of this approach. In this work, poly-L-lactic acid (PLLA) nanoparticles are proposed as a promising solution. Indeed, PLLA is piezoelectric, but also biocompatible, biodegradable, and is a material already approved by the Food and Drug Administration for clinical use. PLLA nanoparticles were fabricated using a single emulsion method, by studying the effect of different parameters (polymer and stabilizer concentration and sonication intensity) on their properties (morphology, size, zeta-potential and crystallinity). To enhance the crystallinity of PLLA nanoparticles, which is related to piezoelectricity, an annealing treatment was pursued. The stability and biodegradability of the nanoparticles were assessed over time in different buffers, recapitulating realistic physiological conditions. Preliminary in vitro tests assessing muscle cell viability upon contact with the nanoparticles were also performed.