Piezoelectric electrospun scaffold incorporating ibuprofen loaded ultrasound-responsive mesoporous silica nanoparticles for tissue regeneration

Abstract

Inflammation plays a pivotal role in tissue repair, and its modulation is crucial to avoid excessive immune activation or suppression. Three-dimensional scaffolds that can control the release of anti-inflammatory agents over time and space offer a promising approach to regulate the immune response while providing structural support during healing. In this study, we developed an electrospun biomimetic scaffold incorporating ibuprofen-loaded mesoporous silica nanoparticles with an ultrasound-responsive alginate coating. Optimal parameters for safe and non-invasive ultrasound stimulation (i.e., frequency, intensity, and duration) were identified to induce weakening of the interaction among the alginate chains, enabling on-demand drug release from the nanoparticles. In vitro studies with human macrophages confirmed the biocompatibility and anti-inflammatory efficacy of the nanoparticles at concentrations up to 1 mg mL⁻¹. The results demonstrated that ultrasound stimulation further amplified the therapeutic effect even at very low concentrations (≥0.05 mg mL⁻¹) of the tested nanoparticle suspensions. The electrospinning process was optimised to produce nanoparticle-containing polyvinylidene fluoride nanofibers that are aligned and piezoelectric, mimicking the architecture and electroactivity of native tissues. The resulting scaffold exhibited excellent biocompatibility and effectively reduced inflammatory markers in vitro. Furthermore, controlled ibuprofen release from the scaffold was successfully triggered on-demand through repeated ultrasound stimulations, applied up to seven days after immersion. By combining structural support, biocompatibility, and the capacity for drug release in response to safe, non-invasive ultrasound stimulations, this scaffold represents a compelling platform for localised modulation of inflammation and the promotion of functional tissue regeneration.