preprints_ui: jy2e7_v1
Data license: ODbL (database) & original licenses (content) · Data source: Open Science Framework
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| jy2e7_v1 | Ultrasound Triggered Gelation to Treat Discogenic Lower Back Pain | Motivation: Lower back pain (LBP) is one of the leading causes of global disability. LBP and related radicular leg pain are closely linked to intervertebral disc (IVD) degeneration, which accounts for approximately 40% of the estimated 619 million LBP cases worldwide. Currently, there are two diametrically opposed treatment options for this condition: conservative physiotherapy to provide temporary relief, or major surgical intervention. Neither has proven to provide suitable long-term outcomes. Emerging strategies focus on injectable biomaterials to provide structural support and facilitate tissue repair, although they are still largely experimental and face several limitations, including limited integration with native tissue. Moreover, the implant formation mechanism may be depth-limited (light curing) or time-constrained (self-curing). Aim: The objective of this research is to demonstrate a new option to restore spinal function through the use of extracorporeal ultrasound to remotely trigger in situ implant formation on demand, such that the clinician can control the process with the timing and location of their choosing. The system concept centers around an implant precursor material consisting of an anionic polysaccharide matrix seeded with thermally sensitive liposomes. Ultrasound-mediated heating on the order of 3-5 degrees above normal body temperature triggers the release of crosslinking species from the liposomes, thereby initiating hydrogel formation. Methods: Candidate polysaccharide and liposome formulations were evaluated for their injectability, loading efficiency, and post-gelation mechanical properties. Ultrasound parameters (frequency, pressure, duty cycle) were optimized for targeted heating efficiency. Techniques for treatment process monitoring and control were independently investigated using thermometry and acoustic cavitation emissions. The material constructs and ultrasound protocols were used together in a series of proof-of-concept experiments using ex vivo bovine IVD specimens, with biomechanical analysis across three states: intact, degenerated, and after ultrasound-triggered implant formation. Results: Extensive testing revealed an optimized implant precursor material consisting of sodium alginate (1.5 wt/v%) seeded with calcium-loaded liposomes (157±9 nm) to enable hyperthermia-triggered release and glass microspheres (6 wt/v%) to ensure preferential ultrasound absorption for safe heating. No significant difference was found between hydrogels heated with an incubator or ultrasound, suggesting comparable calcium release between both methods. Optimal ultrasound parameters for precursor gel heating were found to be 0.95 MHz, 1.6 MPa (peak negative), and 87% duty cycle. Automated treatment control using temperature or cavitation emission measurements both were successfully implemented, with cavitation being preferable for non-invasive implementation. Proof of concept experiments indicated partial restoration of biomechanical function in ex vivo bovine IVDs, with implant material well-integrated into the disc tissue, and without material herniation. Conclusion: We have demonstrated the feasibility of ultrasound-guided hydrogel gelation in situ. These results offer promise for treating spinal disc degeneration, with continued refinement of materials and protocols essential for achieving robust in-disc efficacy. | 2024-12-14T10:09:56.635128 | 2024-12-14T12:02:43.042689 | 2024-12-14T12:02:22.683465 | focusarchive | 1 | accepted | 1 | 1 | https://doi.org/10.31225/osf.io/jy2e7 | CC-By Attribution 4.0 International | [] | Veerle Brans; Anna Constantinou; Luca Bau; Constantin Coussios; Molly Stevens; Michael Gray; Matthew Kibble; Nicolas Newell | [{"id": "bm2a4", "name": "Veerle Brans", "index": 0, "orcid": null, "bibliographic": true}, {"id": "x6g3m", "name": "Anna Constantinou", "index": 1, "orcid": null, "bibliographic": true}, {"id": "v3amz", "name": "Luca Bau", "index": 2, "orcid": null, "bibliographic": true}, {"id": "grf4k", "name": "Constantin Coussios", "index": 3, "orcid": null, "bibliographic": true}, {"id": "5wmzx", "name": "Molly Stevens", "index": 4, "orcid": null, "bibliographic": true}, {"id": "f7mgc", "name": "Michael Gray", "index": 5, "orcid": "0000-0002-3245-3296", "bibliographic": true}, {"id": "wgczh", "name": "Matthew Kibble", "index": 6, "orcid": null, "bibliographic": true}, {"id": "sc4qe", "name": "Nicolas Newell", "index": 7, "orcid": null, "bibliographic": true}] | Veerle Brans | Engineering; Materials Science and Engineering; Biomedical Engineering and Bioengineering | [{"id": "59bacc5654be81033c4e4a6f", "text": "Engineering"}, {"id": "59bacc5854be81033c4e4ad7", "text": "Materials Science and Engineering"}, {"id": "59bacc5a54be81033c4e4b3c", "text": "Biomedical Engineering and Bioengineering"}] | https://osf.io/download/675d59966cb843fc3ef7c15c | 0 | no | not_applicable | [] | 2025-04-09T21:06:15.356151 |