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

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>i.e.</i>, frequency, intensity, and duration) were identified to induce weakening of the interaction among the alginate chains, enabling on-demand drug release from the nanoparticles. <i>In vitro</i> 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 <i>in vitro</i>. 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.