Physical stimuli-emitting scaffolds: The role of piezoelectricity in tissue regeneration

The imbalance between life expectancy and quality of life is increasing due to the raising prevalence of chronic diseases. Musculoskeletal disorders and chronic wounds affect a growing percentage of people and demand more efficient tools for regenerative medicine. Scaffolds that can better mimic the natural physical stimuli that tissues receive under healthy conditions and during healing may significantly aid the regeneration process. Shape, mechanical properties, pore size and interconnectivity have already been demonstrated to be relevant scaffold features that can determine cell adhesion and differentiation. Much less attention has been paid to scaffolds that can deliver more dynamic physical stimuli, such as electrical signals. Recent developments in the precise measurement of electrical fields in vivo have revealed their key role in cell movement (galvanotaxis), growth, activation of secondary cascades, and differentiation to different lineages in a variety of tissues, not just neural. Piezoelectric scaffolds can mimic the natural bioelectric potentials and gradients in an autonomous way by generating the electric stimuli themselves when subjected to mechanical loads or, if the patient or the tissue lacks mobility, ultrasound irradiation. This review provides an analysis on endogenous bioelectrical signals, recent developments on piezoelectric scaffolds for bone, cartilage, tendon and nerve regeneration, and their main outcomes in vivo. Wound healing with piezoelectric dressings is addressed in the last section with relevant examples of performance in animal models. Results evidence that a fine adjustment of material composition and processing (electrospinning, corona poling, 3D printing, annealing) provides scaffolds that act as true emitters of electrical stimuli that activate endogenous signaling pathways for more efficient and long-term tissue repair.