Controlled Degradation of Polycaprolactone Polymers through Ultrasound Stimulation

This study describes the development of an ultrasound-responsive polymer system that provides on-demand degradation when exposed to high-intensity focused ultrasound (HIFU). Diels–Alder cycloadducts were used to crosslink polycaprolactone (PCL) polymers and underwent a retro Diels–Alder reaction when stimulated with HIFU. Two Diels–Alder polymer compositions were explored to evaluate the link between reverse reaction energy barriers and polymer degradation rates. PCL crosslinked with isosorbide was also used as a non-Diels–Alder-based control polymer. An increase of HIFU exposure time and amplitude correlated with an increase of PCL degradation for Diels–Alder-based polymers. Ultrasound imaging during HIFU allowed for real-time visualization of the on-demand degradation through cavitation-based mechanisms. The temperature surrounding the sample was monitored with a thermocouple during HIFU stimulation; a minimal increase in temperature was observed. PCL polymers were characterized using Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), optical profilometry, and mechanical testing. PCL degradation byproducts were identified by mass spectrometry, and their cytocompatibility was evaluated in vitro. Overall, this study demonstrated that HIFU is an effective image-guided, external stimulus to control the degradation of Diels–Alder-based PCL polymers on-demand.