The discovery of piezoelectricity, endogenous electric fields and transmembrane potentials in biological tissues has kindled research and the development of technologies using electrical stimulation for tissue regeneration. Piezoelectric materials generate electrical activity in response to deformations and allow for the delivery of an electrical stimulus without the need for an external power source. As a scaffold for tissue engineering, growing interest exists due to its potential of providing electrical stimulation to cells to promote tissue formation. In this review, we cover the discovery of piezoelectricity in biological tissues, its connection to streaming potentials, biological response to electrical stimulation and commonly used piezoelectric materials for tissue regeneration. This review summarizes their potential as a promising scaffold in the tissue engineering field.

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Polyvinylidine fluoride (PVDF) is being investigated as a potential scaffold for bone tissue engineering because of its proven biocompatibility and piezoelectric property, wherein it can generate electrical activity when mechanically deformed. In this study, PVDF scaffolds were prepared by electrospinning using different voltages (12-30 kV), evaluated for the presence of the piezoelectric β-crystal phase and its effect on biological function. Electrospun PVDF was compared with unprocessed/raw PVDF, films and melt-spun fibers for the presence of the piezoelectric β-phase using differential scanning calorimetry, Fourier transform infrared spectroscopy and x-ray diffraction. The osteogenic differentiation of human mesenchymal stem cells (MSCs) was evaluated on scaffolds electrospun at 12 and 25 kV (PVDF-12 kV and PVDF-25 kV, respectively) and compared to tissue culture polystyrene (TCP). Electrospinning PVDF resulted in the formation of the piezoelectric β-phase with the highest β-phase fraction of 72% for electrospun PVDF at 25 kV. MSCs cultured on both the scaffolds were well attached as indicated by a spread morphology. Cells on PVDF-25 kV scaffolds had the greatest alkaline phosphatase activity and early mineralization by day 10 as compared to TCP and PVDF-12 kV. The results demonstrate the potential for the use of PVDF scaffolds for bone tissue engineering applications.

Biphasic calcium phosphates (BCP) have been sought after as biomaterials for the reconstruction of bone defects in maxillofacial, dental and orthopaedic applications. They have demonstrated proven biocompatibility, osteoconductivity, safety and predictability in in vitro, in vivo and clinical models. More recently, in vitro and in vivo studies have shown that BCP can be osteoinductive. In the field of tissue engineering, they represent promising scaffolds capable of carrying and modulating the behavior of stem cells. This review article will highlight the latest advancements in the use of BCP and the characteristics that create a unique microenvironment that favors bone regeneration.

Human neural stem/progenitor cells (hNSCs/NPCs) are a promising cell source for neural tissue engineering because of their ability to differentiate into various neural lineages. In this study, hNSC/NPC differentiation was evaluated on piezoelectric, fibrous scaffolds. These smart materials have an intrinsic material property where transient electric potential can be generated in the material upon minute mechanical deformation. hNSCs/NPCs cultured on the scaffolds and films differentiated into β-III tubulin-positive cells, a neuronal cell marker, with or without the presence of inductive factors. In contrast, hNSCs/NPCs cultured on laminin-coated plates were predominantly nestin positive, a NSC marker, in the control medium. Gene expression results suggest that the scaffolds may have promoted the formation of mature neural cells exhibiting neuron-like characteristics. hNSCs/NPCs differentiated mostly into β-III tubulin-positive cells and had the greatest average neurite length on micron-sized, annealed (more piezoelectric), aligned scaffolds, demonstrating their potential for neural tissue-engineering applications.