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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 induce the formation of thicker peptide fibrils. (a) TEM images showing morphology of peptide aggregates, samples with a peptide concentration of 20 mg ml–1, 130 mM NaCl in D2O, images taken at ×20 000 magnification, scale bars = 200 nm; top left – P11-8; top right P11-8 : GAG 1 : 10; bottom left P11-12 and bottom right P11-12 : GAG 1 : 10. (b) Optical micrograph of gel in inverted vial from left to right P11-9, P11-9 : GAG 1 : 0.5, P11-9 : GAG 1 : 10, demonstrating self-supporting nature of gels. (c) Optical micrograph of gel in inverted vial taken through polarised lenses from left to right P11-9, P11-9 : GAG 1 : 0.5, P11-9 : GAG 1 : 10, demonstrating birefringence of gels.
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fig3: Glycosaminoglycans induce the formation of thicker peptide fibrils. (a) TEM images showing morphology of peptide aggregates, samples with a peptide concentration of 20 mg ml–1, 130 mM NaCl in D2O, images taken at ×20 000 magnification, scale bars = 200 nm; top left – P11-8; top right P11-8 : GAG 1 : 10; bottom left P11-12 and bottom right P11-12 : GAG 1 : 10. (b) Optical micrograph of gel in inverted vial from left to right P11-9, P11-9 : GAG 1 : 0.5, P11-9 : GAG 1 : 10, demonstrating self-supporting nature of gels. (c) Optical micrograph of gel in inverted vial taken through polarised lenses from left to right P11-9, P11-9 : GAG 1 : 0.5, P11-9 : GAG 1 : 10, demonstrating birefringence of gels.

Mentions: We observe that incorporation of GAGs into peptide hydrogels also modifies their microscopic properties. Transmission electron microscopy images reveal pronounced differences in the fibril morphologies (Fig. 3a and Fig. S2, S3, ESI‡). Broadly speaking, the changes in gel structure between peptide-only and peptide:GAG gels are very similar. In peptide-only gels, the fibril widths are of the order of 10 nm. This compares to peptide:GAG gels where the fibrils align and cluster together with bundle diameters of the order of 100 nm. These results are quantified and presented in Table S2 (ESI‡) for each of the peptides alone and 1 : 10 peptide : GAG mixtures.


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 induce the formation of thicker peptide fibrils. (a) TEM images showing morphology of peptide aggregates, samples with a peptide concentration of 20 mg ml–1, 130 mM NaCl in D2O, images taken at ×20 000 magnification, scale bars = 200 nm; top left – P11-8; top right P11-8 : GAG 1 : 10; bottom left P11-12 and bottom right P11-12 : GAG 1 : 10. (b) Optical micrograph of gel in inverted vial from left to right P11-9, P11-9 : GAG 1 : 0.5, P11-9 : GAG 1 : 10, demonstrating self-supporting nature of gels. (c) Optical micrograph of gel in inverted vial taken through polarised lenses from left to right P11-9, P11-9 : GAG 1 : 0.5, P11-9 : GAG 1 : 10, demonstrating birefringence of gels.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: Glycosaminoglycans induce the formation of thicker peptide fibrils. (a) TEM images showing morphology of peptide aggregates, samples with a peptide concentration of 20 mg ml–1, 130 mM NaCl in D2O, images taken at ×20 000 magnification, scale bars = 200 nm; top left – P11-8; top right P11-8 : GAG 1 : 10; bottom left P11-12 and bottom right P11-12 : GAG 1 : 10. (b) Optical micrograph of gel in inverted vial from left to right P11-9, P11-9 : GAG 1 : 0.5, P11-9 : GAG 1 : 10, demonstrating self-supporting nature of gels. (c) Optical micrograph of gel in inverted vial taken through polarised lenses from left to right P11-9, P11-9 : GAG 1 : 0.5, P11-9 : GAG 1 : 10, demonstrating birefringence of gels.
Mentions: We observe that incorporation of GAGs into peptide hydrogels also modifies their microscopic properties. Transmission electron microscopy images reveal pronounced differences in the fibril morphologies (Fig. 3a and Fig. S2, S3, ESI‡). Broadly speaking, the changes in gel structure between peptide-only and peptide:GAG gels are very similar. In peptide-only gels, the fibril widths are of the order of 10 nm. This compares to peptide:GAG gels where the fibrils align and cluster together with bundle diameters of the order of 100 nm. These results are quantified and presented in Table S2 (ESI‡) for each of the peptides alone and 1 : 10 peptide : GAG mixtures.

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