Construction of piezoelectric, conductive and injectable hydrogels to promote wound healing through electrical stimulation

Abstract

Piezoelectric, conductive, and injectable hydrogel (SPG hydrogel) is constructed to rapidly close wounds, efficiently harvest biomechanical energy from animal motion, and generate electrical stimulation for electrotherapy of wound healing. 3-amino-4-methoxybenzoic acid (AMB) monomer was polymerized and grafted onto the gelatin, which was further crosslinked using EDC/NHS and embedded with strontium titanate nanoparticles (80.5 wt%), forming SPG hydrogel. This SPG hydrogel had high tissue adhesion ability, and could generate the output voltage (maximum output voltage 1 V) and current (maximum output current 0.5 nA) upon mechanical bending, promoting NIH-3T3 cell migration and proliferation. Upon application to the mice wound model, the SPG hydrogel rapidly closed the skin wound, smoothed the wound's appearance, reduced the remaining wound size, and increased epidermal thickness, demonstrating remarkable wound healing capabilities. This study suggests that the body motion-promoted electrotherapy offers a promising strategy for wound healing. STATEMENT OF SIGNIFICANCE: Piezoelectric nanomaterials are often incorporated into hydrogels to create piezoelectric hydrogels for wound healing. However, piezoelectric nanomaterials tend to agglomerate within the hydrogel matrix, and the hydrogel's low conductivity hinders efficient electron transfer. Together, both factors significantly reduce the piezoelectric effect. In this study, we developed an SPG hydrogel to improve the homogeneity and conductivity of the piezoelectric hydrogel. We first designed a conductive PG hydrogel and then immoblized piezoelectric STO nanoparticles within its matrix through coordination chemistry. Upon mechanical deformation, the uniformly distributed STO nanoparticles can generate electricity, which can efficiently transfer through the conductive matrix to the hydrogel's surface. This design shows great potential for wound healing applications.

Keywords: Bioelectricity; Conductive polymer; Injectable hydrogel; Piezoelectric nanomaterials; Wound healing.