Injectable Doubly Cross-Linked Microgels for Improving the Mechanical Properties of Degenerated Intervertebral Discs

• Published in: Biomacromolecules 2012-09, Vol.13 (9), p.2793-2801
• Main Authors: Milani, Amir H, Freemont, Anthony J, Hoyland, Judith A, Adlam, Daman J, Saunders, Brian R
• Format: Article
• Language: English
• Subjects: Animals; Applied sciences; Biocompatible Materials - chemical synthesis; Biocompatible Materials - pharmacology; Biological and medical sciences; Cattle; Collagenases - chemistry; Cross-Linking Reagents - chemistry; Elastic Modulus; Epoxy Compounds - chemistry; Exact sciences and technology; Gels; Hydrogen-Ion Concentration; Injections; Intervertebral Disc - drug effects; Intervertebral Disc - pathology; Intervertebral Disc Degeneration - drug therapy; Intervertebral Disc Degeneration - pathology; Medical sciences; Methacrylates - chemistry; Molecular Structure; Organic polymers; Physicochemistry of polymers; Properties and characterization; Shear Strength; Solution and gel properties; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Technology. Biomaterials. Equipments; Weight-Bearing
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm3007727

The use of injectable pH-responsive doubly cross-linked microgels (DX microgels) to improve the mechanical properties of degenerated intervertebral discs is demonstrated for the first time. The microgel comprised methyl methacrylate (MMA), methacrylic acid (MAA), ethyleneglycol dimethacrylate (EGD) and glycidyl methacrylate (GM) and was poly(MMA/MAA/EGD)-GM. The GM facilitated covalent interparticle cross-linking. The DX microgels are shown to have tunable mechanical properties. Degeneration of model bovine intervertebral discs (IVDs) was induced using collagenase. When injected into degenerated IVDs the DX microgels were shown to improve the strain, modulus, toughness and resilience. The extent of mechanical property improvement was an increasing function of DX microgel concentration, suggesting tunability. Cytotoxicity studies showed that the DX microgel was biocompatible under the conditions investigated. The results of this study imply that injectable DX microgels have good potential as a future regenerative medicine strategy for restoring the mechanical properties of degenerated load-bearing soft tissue, such as IVDs.