Ultrasound-triggered in situ hydrogel formation for spinal disc repair

Abstract

Over 600 million people suffer from lower back pain attributable to spinal disc degeneration. Treatments range from conservative physiotherapy to costly, invasive options like spinal fusion surgery. Injectable engineered materials may allow minimally invasive disc repair, but self-curing lacks process control, and optical in situ curing is depth-limited. We, therefore, propose ultrasound-triggered implant formation, enabling spatiotemporal control at clinically relevant tissue depths. We developed an anionic polysaccharide-based hydrogel, seeded with calcium-loaded thermosensitive liposomes. Focused ultrasound was used to heat this injectable precursor material to just above the lipid phase-transition temperature of 41 °C, inducing calcium release and ionically crosslinked network formation. Controlled heating was achieved by elevating the acoustic attenuation of the precursor solution with purified glass microspheres. The heating and gelation processes were controlled in real-time using thermometry and acoustic cavitation emissions. We optimized the ultrasound frequency and pressure amplitude to provide controlled heating with minimal cavitation. After these parameters were employed for ultrasound-mediated gelation, the rheological properties of the resultant gels were compared to literature values for native spinal disc material. Finally, in situ gel formation was evaluated in ex vivo bovine tail discs, from injection to mechanical assessments, confirming the ability to remotely trigger injectable disc-mimicking materials.