Injectable hydrogels with high fixed charge density and swelling pressure for nucleus pulposus repair: biomimetic glycosaminoglycan analogues

S.S. Sivan, S. Roberts, J.P.G. Urban, J. Menage, J. Bramhill, D. Campbell, V.J. Franklin, F. Lydon, Y. Merkher, A. Maroudas, B.J. Tighe

Research output: Contribution to journalArticle

Abstract

The load-bearing biomechanical role of the intervertebral disc is governed by the composition and organization of its major macromolecular components, collagen and aggrecan. The major function of aggrecan is to maintain tissue hydration, and hence disc height, under the high loads imposed by muscle activity and body weight. Key to this role is the high negative fixed charge of its glycosaminoglycan side chains, which impart a high osmotic pressure to the tissue, thus regulating and maintaining tissue hydration and hence disc height under load. In degenerate discs, aggrecan degrades and is lost from the disc, particularly centrally from the nucleus pulposus. This loss of fixed charge results in reduced hydration and loss of disc height; such changes are closely associated with low back pain. The present authors developed biomimetic glycosaminoglycan analogues based on sulphonate-containing polymers. These biomimetics are deliverable via injection into the disc where they polymerize in situ, forming a non-degradable, nuclear "implant" aimed at restoring disc height to degenerate discs, thereby relieving back pain. In vitro, these glycosaminoglycan analogues possess appropriate fixed charge density, hydration and osmotic responsiveness, thereby displaying the capacity to restore disc height and function. Preliminary biomechanical tests using a degenerate explant model showed that the implant adapts to the space into which it is injected and restores stiffness. These hydrogels mimic the role taken by glycosaminoglycans in vivo and, unlike other hydrogels, provide an intrinsic swelling pressure, which can maintain disc hydration and height under the high and variable compressive loads encountered in vivo.
Original languageEnglish
Pages (from-to)1124-1133
Number of pages10
JournalActa Biomaterialia
Volume10
Issue number3
Early online date21 Nov 2013
DOIs
Publication statusPublished - 1 Mar 2014

Fingerprint

Biomimetics
Hydrogels
Glycosaminoglycans
Charge density
Aggrecans
Swelling
Repair
Pressure
Injections
Hydration
Intervertebral Disc
Osmotic Pressure
Weight-Bearing
Back Pain
Low Back Pain
Tissue
Polymers
Collagen
Body Weight
Bearings (structural)

Bibliographical note

Funding: Engineering and Physical Science Research Council [GR/S41197/01]; Marie-Curie Intra European Fellowship (NovoDisc) [MEIF-CT-2005-025147]; Charles W. McCutchen Foundation

Keywords

  • hydrogel
  • intervertebral disc
  • Glycosaminoglycan disc repair
  • swelling pressure
  • minimally invasive

Cite this

Sivan, S.S. ; Roberts, S. ; Urban, J.P.G. ; Menage, J. ; Bramhill, J. ; Campbell, D. ; Franklin, V.J. ; Lydon, F. ; Merkher, Y. ; Maroudas, A. ; Tighe, B.J. / Injectable hydrogels with high fixed charge density and swelling pressure for nucleus pulposus repair : biomimetic glycosaminoglycan analogues. In: Acta Biomaterialia. 2014 ; Vol. 10, No. 3. pp. 1124-1133.
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Injectable hydrogels with high fixed charge density and swelling pressure for nucleus pulposus repair : biomimetic glycosaminoglycan analogues. / Sivan, S.S.; Roberts, S.; Urban, J.P.G.; Menage, J.; Bramhill, J.; Campbell, D.; Franklin, V.J.; Lydon, F.; Merkher, Y.; Maroudas, A.; Tighe, B.J.

In: Acta Biomaterialia, Vol. 10, No. 3, 01.03.2014, p. 1124-1133.

Research output: Contribution to journalArticle

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T1 - Injectable hydrogels with high fixed charge density and swelling pressure for nucleus pulposus repair

T2 - biomimetic glycosaminoglycan analogues

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AU - Roberts, S.

AU - Urban, J.P.G.

AU - Menage, J.

AU - Bramhill, J.

AU - Campbell, D.

AU - Franklin, V.J.

AU - Lydon, F.

AU - Merkher, Y.

AU - Maroudas, A.

AU - Tighe, B.J.

N1 - Funding: Engineering and Physical Science Research Council [GR/S41197/01]; Marie-Curie Intra European Fellowship (NovoDisc) [MEIF-CT-2005-025147]; Charles W. McCutchen Foundation

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N2 - The load-bearing biomechanical role of the intervertebral disc is governed by the composition and organization of its major macromolecular components, collagen and aggrecan. The major function of aggrecan is to maintain tissue hydration, and hence disc height, under the high loads imposed by muscle activity and body weight. Key to this role is the high negative fixed charge of its glycosaminoglycan side chains, which impart a high osmotic pressure to the tissue, thus regulating and maintaining tissue hydration and hence disc height under load. In degenerate discs, aggrecan degrades and is lost from the disc, particularly centrally from the nucleus pulposus. This loss of fixed charge results in reduced hydration and loss of disc height; such changes are closely associated with low back pain. The present authors developed biomimetic glycosaminoglycan analogues based on sulphonate-containing polymers. These biomimetics are deliverable via injection into the disc where they polymerize in situ, forming a non-degradable, nuclear "implant" aimed at restoring disc height to degenerate discs, thereby relieving back pain. In vitro, these glycosaminoglycan analogues possess appropriate fixed charge density, hydration and osmotic responsiveness, thereby displaying the capacity to restore disc height and function. Preliminary biomechanical tests using a degenerate explant model showed that the implant adapts to the space into which it is injected and restores stiffness. These hydrogels mimic the role taken by glycosaminoglycans in vivo and, unlike other hydrogels, provide an intrinsic swelling pressure, which can maintain disc hydration and height under the high and variable compressive loads encountered in vivo.

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