Hybrid biodegradable 3D scaffolds based on piezoelectric poly(3-hydroxybutyrate) for tissue engineering

Endogenous bioelectrical signals are one of the most relevant cues to determine tissue function in electrosensitive tissues and thus play a vital role in the tissue regeneration process. In this regard, piezoelectricity is considered as one of the key functionalities in biomaterials to electrically stimulate tissue regeneration. However, the integration of biocompatibility, biodegradability and 3D structure with pronounced piezoelectric activity to support tissues repair remains a challenge. Furthermore, the mere presence of a matrix for cell growth is often not sufficient for a good cell adhesion and proliferation; this often requires other components, which would provide additional functionalities, for example, improve cell adhesion and proliferation, provide antibacterial protection, etc (polymers, nano- and micro- particles, biological molecules, such as enzymes, and antibiotics). That stimulates development of hybrid polymer-based materials incorporating both organic and inorganic components. Composite biodegradable and piezoelectric polymer-based materials are emerging as a very potent and promising class of materials due to their diverse properties, which are proved to be a viable tool for tissue engineering applications for the formation of the extracellular matrix (ECM), avoiding a second surgery, and providing electrical stimulation. In this work, novel hybrid 3-D electrospun scaffolds are developed to improve cell adhesion and proliferation, biomimetic mineralization, and antibacterial activity. These scaffolds are based on biodegradable natural poly(3-hydroxybutyrete) polymer, which has piezoelectric properties relevant for a close contact to bone tissue. Specifically in this thesis work: 1) it has been demonstrated, for the first time to the best of our knowledge, that under dynamically applied mechanical stress, piezoelectric PHB-based scaffolds are capable of providing an enhanced biomimetic mineralization and more homogenous growth of the inorganic bone phases, such as calcium carbonate, resulting in an improved cell adhesion and proliferation; 2) design of composite PHB-based scaffolds is pursued by functionalizing it with CaCO3 particles and subsequent drug immobilization, which results in an enhanced osteoblastic cell adhesion/proliferation and 17 pronounced antibacterial effects; 3) surface functionalization of electrospun PHB-based scaffolds is performed close to surface monomolecular level by a non-destructive diazonium approach, leading to preserved piezoresponses and an improved wettability, which are important for cell adhesion for regenerative tissue engineering; 4) design of hybrid biodegradable PHB-based scaffolds are pursued by their functionalization with reduced graphene oxide (rGO) nanoflakes, resulting in an enhanced surface potential and piezoresponses, demonstrating improved cell adhesion and proliferation under static and dynamic mechanical conditions; 5) investigation of the biodegradation process and studies of its impact on the composition, structure, physio-mechanical and electromechanical properties of hybrid PHB-rGO scaffolds with an enhanced piezoresponses are performed. Our results emphasize the added value of hybrid biodegradable and piezoelectric polymer-based materials and approaches, particularly involving functionalization by microparticles, surface chemistry and bioactive molecules. Such new materials are envisioned to find applications in tissue engineering, biomedicine, and biology