title: Peptide:glycosaminoglycan hybrid hydrogels as an injectable intervention for spinal disc degeneration.
abstract: Degeneration of the spinal discs is a major cause of back pain. During the degeneration process, there is a loss of glycosaminoglycans (GAGs) from the proteoglycan-rich gel in the disc's nucleus, which adversely alters biomechanical performance. Current surgical treatments for back pain are highly invasive and have low success rates; there is an urgent need for minimally-invasive approaches that restore the physiological mechanics of the spine. Here we present an injectable peptide:GAG hydrogel that rapidly self-assemblesin situand restores the mechanics of denucleated intervertebral discs. It forms a gel with comparable mechanical properties to the native tissue within seconds to minutes depending on the peptide chosen. Unlike other biomaterials that have been proposed for this purpose, these hybrid hydrogels can be injected through a very narrow 25 G gauge needle, minimising damage to the surrounding soft tissue, and they mimic the ability of the natural tissue to draw in water by incorporating GAGs. Furthermore, the GAGs enhance the gelation kinetics and thermodynamic stability of peptide hydrogels, significantly reducing effusion of injected material from the intervertebral disc (GAG leakage of 8 ± 3% after 24 h when peptide present, compared to 39 ± 3% when no peptide present). In anex vivomodel, we demonstrate that the hydrogels can restore the compressive stiffness of denucleated bovine intervertebral discs. Compellingly, this novel biomaterial has the potential to transform the clinical treatment of back pain by resolving current surgical challenges, thus improving patient quality of life.
authors.affiliation: Institute of Medical and Biological Engineering , University of Leeds , Leeds , LS2 9JT , UK . Email: r.k.wilcox@leeds.ac.uk; School of Chemistry , University of Leeds , Leeds , LS2 9JT , UK . Email: p.a.beales@leeds.ac.uk.
authors.forename: D E
authors.initials: DE
authors.lastname: Miles
authors.affiliation: Institute of Medical and Biological Engineering , University of Leeds , Leeds , LS2 9JT , UK . Email: r.k.wilcox@leeds.ac.uk; School of Biomedical Sciences , University of Leeds , Leeds , LS2 9JT , UK.
authors.forename: E A
authors.initials: EA
authors.lastname: Mitchell
authors.affiliation: School of Mechanical Engineering , University of Leeds , Leeds , LS2 9JT , UK.
authors.forename: N
authors.initials: N
authors.lastname: Kapur
authors.affiliation: School of Chemistry , University of Leeds , Leeds , LS2 9JT , UK . Email: p.a.beales@leeds.ac.uk; Astbury Centre for Structural Molecular Biology , University of Leeds , Leeds , LS2 9JT , UK.
authors.forename: P A
authors.initials: PA
authors.lastname: Beales
authors.affiliation: Institute of Medical and Biological Engineering , University of Leeds , Leeds , LS2 9JT , UK . Email: r.k.wilcox@leeds.ac.uk; School of Mechanical Engineering , University of Leeds , Leeds , LS2 9JT , UK.
authors.forename: R K
authors.initials: RK
authors.lastname: Wilcox