Piezoelectric smart biomaterials for bone and cartilage tissue engineering

Abstract

Tissues like bone and cartilage are remodeled dynamically for their functional requirements by signaling pathways. The signals are controlled by the cells and extracellular matrix and transmitted through an electrical and chemical synapse. Scaffold-based tissue engineering therapies largely disturb the natural signaling pathways, due to their rigidity towards signal conduction, despite their therapeutic advantages. Thus, there is a high need of smart biomaterials, which can conveniently generate and transfer the bioelectric signals analogous to native tissues for appropriate physiological functions. Piezoelectric materials can generate electrical signals in response to the applied stress. Furthermore, they can stimulate the signaling pathways and thereby enhance the tissue regeneration at the impaired site. The piezoelectric scaffolds can act as sensitive mechanoelectrical transduction systems. Hence, it is applicable to the regions, where mechanical loads are predominant. The present review is mainly concentrated on the mechanism related to the electrical stimulation in a biological system and the different piezoelectric materials suitable for bone and cartilage tissue engineering.

Keywords: Bone; Cartilage; Electroactive scaffolds; Mechanical stimulation; Piezoelectric materials; Piezoelectricity; Tissue regeneration.

Fig. 1

Illustration shows the highly vascularized ECM of bone (Bone ECM) and avascular ECM of cartilage (cartilage ECM)

Fig. 2

Schematic diagram of ca²⁺ signal transduction pathway and other miscellaneous pathways activate in response to the electrical and mechanical stimulations. The mechanical stimulation on piezoelectric scaffold will result in the electrical signal generation and which will stimulate the voltage-gated ca²⁺ channel. Further increase in the intracellular Ca²⁺ concentration activates the calmodulin (an abbreviation of the calcium-modulated protein) and which will further activate the calcineurin (calcium and calmodulin-dependent serine/threonine protein phosphatase). The activated calcineurin dephosphorylates the NF-AT and it will translocate to the nucleus, where it acts in conjunction with other associated proteins as transcription factors. Also the mechanical stimulation itself can activate the mechanoreceptors present in the membrane and which will lead to the activation of PKC and MAPK signaling cascades. These cascades will result in the synthesis of proteoglycan and inhibition of IL-1, responsible for the breakdown of proteoglycan

Scheme 1

Representing the tissue regeneration in response to the mechanical stimulation on the piezoelectric scaffold. The mechanical force on the piezoelectric scaffold generates the electrical stimulus for enhanced tissue regeneration. At the same time, applied mechanical stress can simultaneously augments the tissue regeneration in predefined signaling pathways

Fig. 3

Electrical stimulation to cells by internalized BNNT nanoparticle as a result of external ultrasound irradiation. The direct piezoelectric effect applied on BNNTs and ultrasonic wave as mechanical stress to convert into electrical stimuli for enhanced cell differentiation