Ultrasound-Triggered Gelation for Restoring Biomechanical Properties of Degenerated Functional Spinal Units.

Abstract

Lower back pain is closely associated with intervertebral disc (IVD) degeneration and is a leading cause of global disability. Existing treatment options are unable to provide suitable long-term outcomes, and emerging strategies employing injectable biomaterials are hindered by factors including limited native tissue integration and depth- or time-constrained gelation mechanisms. To overcome these issues, the present research evaluates a new concept employing ultrasound to remotely trigger in situ implant formation. The concept centers around an implant precursor biomaterial consisting of an anionic polysaccharide solution containing thermally sensitive liposomes loaded with ionic crosslinkers. Ultrasound-mediated heating to 4-5 °C above normal body temperature triggers liposomal release of the crosslinking species, thereby initiating hydrogel formation. Optimization studies define the implant precursor material (1.5% wt/v sodium alginate seeded with calcium-loaded liposomes (10-15 mm calcium chloride) and 6% wt/v glass microspheres) and the ultrasound parameters (0.95 MHz, 1.6 MPa amplitude, 87% duty cycle). Proof-of-concept experiments in degenerated ex vivo bovine IVDs indicate partial restoration of biomechanical function, with the implanted biomaterial well-integrated into the disc tissue and without material herniation. These results offer promise for treating intervertebral disc degeneration, with continued refinement of biomaterials and protocols being essential for achieving robust in-disc efficacy.