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Peptide:glycosaminoglycan hybrid hydrogels as an injectable intervention for spinal disc degeneration.

Miles DE, Mitchell EA, Kapur N, Beales PA, Wilcox RK - J Mater Chem B Mater Biol Med (2016)

Bottom Line: 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 an ex vivo model, 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.

View Article: PubMed Central - PubMed

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.

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-assembles in situ and 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 an ex vivo model, 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.

No MeSH data available.


Related in: MedlinePlus

Glycosaminoglycans promote β-sheet peptide fibril formation. (a) Apparent critical concentration for aggregation as determined by 1H NMR for peptide only and peptide : GAG 1 : 10 samples, 130 mM NaCl and 1.25 mM TMSP in D2O. The table (inset) summarises the net charge and amino acid basis of the peptides. (b) Band fitted FTIR amide I′ region of P11-8, P11-8 : GAG 1 : 10, P11-12 and P11-12 : GAG, 1 : 10, red = fitted spectra, black = processed spectra, all other colours = various amide I′ component peaks. (c) Percentage β-sheet as determined by FTIR for peptide only and peptide : GAG 1 : 10 samples in 130 mM NaCl in D2O.
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fig2: Glycosaminoglycans promote β-sheet peptide fibril formation. (a) Apparent critical concentration for aggregation as determined by 1H NMR for peptide only and peptide : GAG 1 : 10 samples, 130 mM NaCl and 1.25 mM TMSP in D2O. The table (inset) summarises the net charge and amino acid basis of the peptides. (b) Band fitted FTIR amide I′ region of P11-8, P11-8 : GAG 1 : 10, P11-12 and P11-12 : GAG, 1 : 10, red = fitted spectra, black = processed spectra, all other colours = various amide I′ component peaks. (c) Percentage β-sheet as determined by FTIR for peptide only and peptide : GAG 1 : 10 samples in 130 mM NaCl in D2O.

Mentions: We find that in physiological-like conditions the glutamine based P11-4 and P11-8 have a lower residual monomer concentration than their serine analogues P11-9 and P11-12 (Fig. 2a). This is in agreement with our previous work that has shown that the thermodynamics and kinetics of peptide self-assembly are strongly dependent upon the peptide's primary structure.26–28 Significant to the work reported here, we showed that the glutamine-based peptides had significantly lower critical aggregation concentrations (c*) than their serine-based analogues. We conclude that our selection of β-fibril forming peptide variants will be an important control parameter for the design of the self-assembling hydrogel.


Peptide:glycosaminoglycan hybrid hydrogels as an injectable intervention for spinal disc degeneration.

Miles DE, Mitchell EA, Kapur N, Beales PA, Wilcox RK - J Mater Chem B Mater Biol Med (2016)

Glycosaminoglycans promote β-sheet peptide fibril formation. (a) Apparent critical concentration for aggregation as determined by 1H NMR for peptide only and peptide : GAG 1 : 10 samples, 130 mM NaCl and 1.25 mM TMSP in D2O. The table (inset) summarises the net charge and amino acid basis of the peptides. (b) Band fitted FTIR amide I′ region of P11-8, P11-8 : GAG 1 : 10, P11-12 and P11-12 : GAG, 1 : 10, red = fitted spectra, black = processed spectra, all other colours = various amide I′ component peaks. (c) Percentage β-sheet as determined by FTIR for peptide only and peptide : GAG 1 : 10 samples in 130 mM NaCl in D2O.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4920072&req=5

fig2: Glycosaminoglycans promote β-sheet peptide fibril formation. (a) Apparent critical concentration for aggregation as determined by 1H NMR for peptide only and peptide : GAG 1 : 10 samples, 130 mM NaCl and 1.25 mM TMSP in D2O. The table (inset) summarises the net charge and amino acid basis of the peptides. (b) Band fitted FTIR amide I′ region of P11-8, P11-8 : GAG 1 : 10, P11-12 and P11-12 : GAG, 1 : 10, red = fitted spectra, black = processed spectra, all other colours = various amide I′ component peaks. (c) Percentage β-sheet as determined by FTIR for peptide only and peptide : GAG 1 : 10 samples in 130 mM NaCl in D2O.
Mentions: We find that in physiological-like conditions the glutamine based P11-4 and P11-8 have a lower residual monomer concentration than their serine analogues P11-9 and P11-12 (Fig. 2a). This is in agreement with our previous work that has shown that the thermodynamics and kinetics of peptide self-assembly are strongly dependent upon the peptide's primary structure.26–28 Significant to the work reported here, we showed that the glutamine-based peptides had significantly lower critical aggregation concentrations (c*) than their serine-based analogues. We conclude that our selection of β-fibril forming peptide variants will be an important control parameter for the design of the self-assembling hydrogel.

Bottom Line: 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 an ex vivo model, 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.

View Article: PubMed Central - PubMed

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.

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-assembles in situ and 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 an ex vivo model, 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.

No MeSH data available.


Related in: MedlinePlus