title: Injectable hydrogels with high fixed charge density and swelling pressure for nucleus pulposus repair: biomimetic glycosaminoglycan analogues.
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.
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK; Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel; Department of Biotechnology Engineering, ORT Braude College of Engineering, Karmiel 21982, Israel. Electronic address: sivan.sarit@gmail.com.
authors.forename: S S
authors.initials: SS
authors.lastname: Sivan
authors.affiliation: Spinal Studies, RJAH Orthopaedic Hospital & ISTM, Keele University, Oswestry, Shropshire SY10 7AG, UK.
authors.forename: S
authors.initials: S
authors.lastname: Roberts
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK.
authors.forename: J P G
authors.initials: JP
authors.lastname: Urban
authors.affiliation: Spinal Studies, RJAH Orthopaedic Hospital & ISTM, Keele University, Oswestry, Shropshire SY10 7AG, UK.
authors.forename: J
authors.initials: J
authors.lastname: Menage
authors.affiliation: Biomaterials Research Unit, School of Engineering and Applied Science, Aston University, Birmingham B4 7ET, UK.
authors.forename: J
authors.initials: J
authors.lastname: Bramhill
authors.affiliation: Biomaterials Research Unit, School of Engineering and Applied Science, Aston University, Birmingham B4 7ET, UK.
authors.forename: D
authors.initials: D
authors.lastname: Campbell
authors.affiliation: Biomaterials Research Unit, School of Engineering and Applied Science, Aston University, Birmingham B4 7ET, UK.
authors.forename: V J
authors.initials: VJ
authors.lastname: Franklin
authors.affiliation: Biomaterials Research Unit, School of Engineering and Applied Science, Aston University, Birmingham B4 7ET, UK.
authors.forename: F
authors.initials: F
authors.lastname: Lydon
authors.affiliation: Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Merkher
authors.affiliation: Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Maroudas
authors.affiliation: Biomaterials Research Unit, School of Engineering and Applied Science, Aston University, Birmingham B4 7ET, UK.
authors.forename: B J
authors.initials: BJ
authors.lastname: Tighe
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000494:pharmacology*; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000494:pharmacology; D055119:Elastic Modulus / Q000187:drug effects; D006025:Glycosaminoglycans / Q000494:pharmacology*; D020100:Hydrogels / Q000737:chemistry* / Q000494:pharmacology*; D007267:Injections; D007403:Intervertebral Disc / Q000187:drug effects / Q000473:pathology*; D009994:Osmolar Concentration; D009997:Osmotic Pressure / Q000187:drug effects*; D055672:Static Electricity; D034421:Sus scrofa; D013997:Time Factors; D014783:Viscosity / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D003432:Cross-Linking Reagents; D006025:Glycosaminoglycans; D020100:Hydrogels
keywords: Glycosaminoglycan Disc repair; Hydrogel; Intervertebral disc; mnimally invasive; swelling pressure