Injectable carrageenan-based hydrogel with piezoelectric particles for potential regenerative applications.

Abstract

Injectable hydrogels represent a promising strategy for minimally invasive regenerative medicine, enabling the delivery of biomimetic microenvironments directly to irregular tissue defects. Here, we present a multi-responsive, ECM-like injectable hydrogel based on κ/λ-carrageenan, hyaluronic acid, and type I collagen, designed to combine ion-triggered gelation with ultrasound-activated piezoelectric functionality. Gelation occurs rapidly upon exposure to physiological ions, allowing straightforward injection through fine-gauge needles without the need for external crosslinkers or harsh conditions. The incorporation of submicrometric barium titanate particles confers piezoelectric responsiveness, enabling the conversion of ultrasound-induced mechanical stimuli into localised electrical cues. The resulting hydrogels exhibit mechanical properties (Young's modulus 4-9 kPa) and viscoelastic behaviour comparable to native soft tissues, alongside a highly interconnected porous architecture suitable for mass transport and cell infiltration. In vitro studies demonstrate cytocompatibility with fibroblasts, myoblasts, neuronal-like cells, and macrophages, supporting cell viability and proliferation while promoting a pro-regenerative macrophage phenotype. Preliminary ultrasound stimulation experiments confirm that piezoelectric activation does not impair cell viability, establishing a safe basis for future functional investigations. Overall, this work introduces a user-friendly, cost-effective, and multifunctional injectable hydrogel platform with potential for minimally invasive and remotely activated regenerative therapies.