Controlled Degradation of Polycaprolactone Polymers through Ultrasound Stimulation

This study describes the development of an ultrasound-responsivepolymer system that provides on-demand degradation when exposed tohigh-intensity focused ultrasound (HIFU). Diels-Alder cycloadductswere used to crosslink polycaprolactone (PCL) polymers and underwenta retro Diels-Alder reaction when stimulated with HIFU. TwoDiels-Alder polymer compositions were explored to evaluatethe link between reverse reaction energy barriers and polymer degradationrates. PCL crosslinked with isosorbide was also used as a non-Diels-Alder-basedcontrol polymer. An increase of HIFU exposure time and amplitude correlatedwith an increase of PCL degradation for Diels-Alder-based polymers.Ultrasound imaging during HIFU allowed for real-time visualizationof the on-demand degradation through cavitation-based mechanisms.The temperature surrounding the sample was monitored with a thermocoupleduring HIFU stimulation; a minimal increase in temperature was observed.PCL polymers were characterized using Fourier transform infrared (FTIR)spectroscopy, nuclear magnetic resonance (NMR), differential scanningcalorimetry (DSC), optical profilometry, and mechanical testing. PCLdegradation byproducts were identified by mass spectrometry, and theircytocompatibility was evaluated in vitro. Overall,this study demonstrated that HIFU is an effective image-guided, externalstimulus to control the degradation of Diels-Alder-based PCLpolymers on-demand.