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

被引:72
作者
Milani, Amir H. [1 ]
Freemont, Anthony J. [2 ]
Hoyland, Judith A. [2 ]
Adlam, Daman J. [2 ]
Saunders, Brian R. [1 ]
机构
[1] Univ Manchester, Sch Mat, Manchester Mat Sci Ctr, Biomat Res Grp, Manchester M13 9PL, Lancs, England
[2] Univ Manchester, Sch Med, Dev Biomed Res Grp, Manchester M13 9PT, Lancs, England
关键词
HUMAN NUCLEUS PULPOSUS; LINKING POLYMER; COMPRESSION; HYDROGELS; REPAIR; REGENERATION;
D O I
10.1021/bm3007727
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2793 / 2801
页数:9
相关论文
共 39 条
[1]  
Anderson D Greg, 2005, Spine J, V5, p297S, DOI 10.1016/j.spinee.2005.02.019
[2]   The correspondence between equilibrium biphasic and triphasic material properties in mixture models of articular cartilage [J].
Ateshian, GA ;
Chahine, NO ;
Basalo, IM ;
Hung, CT .
JOURNAL OF BIOMECHANICS, 2004, 37 (03) :391-400
[3]   Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells [J].
Benoit, Danielle S. W. ;
Schwartz, Michael P. ;
Durney, Andrew R. ;
Anseth, Kristi S. .
NATURE MATERIALS, 2008, 7 (10) :816-823
[4]   Injectable biomaterials and vertebral endplate treatment for repair and regeneration of the intervertebral disc [J].
Boyd, Lawrence M. ;
Carter, Andrew J. .
EUROPEAN SPINE JOURNAL, 2006, 15 (Suppl 3) :S414-S421
[5]   Engineering alginate for intervertebral disc repair [J].
Bron, Johannes L. ;
Vonk, Lucienne A. ;
Smit, Theodoor H. ;
Koenderink, Gijsje H. .
JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS, 2011, 4 (07) :1196-1205
[6]   Synthetically Simple, Highly Resilient Hydrogels [J].
Cui, Jun ;
Lackey, Melissa A. ;
Madkour, Ahmad E. ;
Saffer, Erika M. ;
Griffin, David M. ;
Bhatia, Surita R. ;
Crosby, Alfred J. ;
Tew, Gregory N. .
BIOMACROMOLECULES, 2012, 13 (03) :584-588
[7]  
Debnath S, 2009, J ENG FIBER FABR, V4, P14
[8]  
FRYMOYER JW, 1991, ORTHOP CLIN N AM, V22, P263
[9]   Reversible Inter- and Intra-Microgel Cross-Linking Using Disulfides [J].
Gaulding, Jeffrey C. ;
Smith, Michael H. ;
Hyatt, John S. ;
Fernandez-Nieves, Alberto ;
Lyon, L. Andrew .
MACROMOLECULES, 2012, 45 (01) :39-45
[10]   Viscoelastic and Mechanical Behavior of Hydrophobically Modified Hydrogels [J].
Hao, Jinkun ;
Weiss, R. A. .
MACROMOLECULES, 2011, 44 (23) :9390-9398