Design and optimization of piezoelectric organic nano transducers for biomedical applications

The exploration of piezoelectric organic nano-transducers stands at the forefront of biomedical engineering, offering promising avenues for advanced applications. This endeavor entails a multidisciplinary approach, amalgamating materials science, nanotechnology, and biomedical engineering. Piezoelectricity is a property where certain materials can be polarized when subjected to mechanical stress and undergo minute deformation when small voltages are applied, forming the foundation of these nano transducers. Piezoelectric organic materials, with their inherent flexibility, lightweight nature, and compatibility with biological environments, have emerged as promising candidates for piezoelectric applications in the biomedical domain. Harnessing the power of organic nano transducers opens up new possibilities for non-invasive sensing, imaging, and therapeutic interventions within the human body. They can be implemented in hardly accessible anatomical districts, developing local electrical impulses thanks to simple environmental stimuli (mechanical waves such as sounds or ultrasounds, US) that can be achieved even in a wireless mode. In diagnostic settings, these transducers enable high-resolution imaging with unprecedented sensitivity, facilitating early disease detection at the molecular level. Integration into wearable devices enables continuous monitoring of physiological parameters, offering personalized healthcare solutions. Therapeutically, these transducers hold promise for targeted drug delivery, precise and controlled release of therapeutic agents, neuromodulation, and tissue engineering. However, characterizing soft piezoelectric polymers at the nanoscale poses significant challenges. Traditional methods like piezo response force microscopy (PFM) in contact mode yield inaccurate results due to the softness of polymers. A novel approach utilizing non-contact PFM in constant excitation and frequency modulation mode has been developed to address this challenge, enabling accurate measurement of piezoelectric coefficients at the nanoscale. The present thesis delves into the design and optimization of these organic transducers, focusing on fundamental principles, unique characteristics, and transformative impact on biomedical diagnostics and therapies. Chapter 2 discusses the development and application of a PVDF-TrFE/Barium Titanate nanocomposite film for bone tissue regeneration. A multimodal bioreactor integrating this film was developed, allowing for mechanical stimulation of the cell-seeded piezoelectric film via fluid dynamics and an ultrasonic field. Results indicate enhanced cell differentiation and matrix deposition compared to conventional methods. Chapter 3 explores the application of ultrasound-stimulated PVDF-TrFE nanoparticles for modulating microglia activation against glioblastoma tumours. Significant anti-cancer activity is achieved by inducing a shift from the M2 pro-tumorigenic phenotype to the M1 pro-inflammatory phenotype in microglia through the controlled and localized piezoelectric-transduced electrical stimulus. This approach presents a novel strategy for glioma immunotherapy. Despite their potential, PVDF and its copolymers have environmental and human safety drawbacks due to potential toxic remnants. The emergence of biodegradable piezoelectric polymers, including natural polysaccharides like chitosan, offers safer and “green” renewable alternatives. Chitosan, derived from chitin, exhibits piezoelectric properties, high biocompatibility and biodegradability, making it suitable for various biomedical applications. Chapter 4 discusses the development and characterization of piezoelectric bio-nanomaterials based on chitosan. Preliminary studies reveal macro and nano piezoelectricity in the developed chitosan film. However, achieving stable nanoparticles for direct piezoelectric measurement remains challenging, necessitating further research. In conclusion, this thesis investigates piezoelectric organic bio-nano transducers, presenting exciting prospects for biomedical applications. These transducers promise to revolutionize medical diagnostics and therapies. Continued research is vital to thoroughly exploit their potential for advanced and personalized healthcare solutions.