journal article·2018-07-10Open access

Incorporation of Collagen and Hyaluronic Acid to Enhance the Bioactivity of Fibrin-Based Hydrogels for Nucleus Pulposus Regeneration

Jennifer Gansau, Conor Timothy Buckley

Abstract

Hydrogels, such as fibrin, offer a promising delivery vehicle to introduce cells into the intervertebral disc (IVD) to regenerate damaged disc tissue as a potential treatment for low back pain. However, fibrin lacks key extracellular matrix (ECM) components, such as collagen (Col) and hyaluronan (HA), normally found in native nucleus pulposus (NP) tissue. The overall aim of this work was to create a fibrin-based hydrogel, by incorporating Col and HA into the matrix to enhance NP-like matrix accumulation using articular chondrocytes (CC). Firstly, we assessed the effect of fibrin concentrations on hydrogel stability, and the viability and proliferation kinetics of articular chondrocytes. Secondly, we investigated the effect of incorporating Col and HA to enhance NP-like matrix accumulation, and finally, examined the influence of various HA concentrations. Results showed that increasing fibrin concentration enhanced cell viability and proliferation. Interestingly, incorporation of HA promoted sGAG accumulation and tended to suppress collagen formation at higher concentrations. Taken together, these results suggest that incorporation of ECM components can enhance the bioactivity of fibrin-based hydrogels, which may help advance the clinical potential of commercial cell and biomaterial ventures in the treatment of IVD regeneration.
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Research context

OpenAlex topics: Spine and Intervertebral Disc Pathology · Musculoskeletal pain and rehabilitation · Shoulder Injury and Treatment

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, 2 Dublin, Ireland

School of Engineering, Trinity College Dublin, 2 Dublin, Ireland

Advanced Materials and Bioengineering Research (AMBER) Centre, Royal College of Surgeons in Ireland & Trinity College Dublin, 2 Dublin, Ireland

Funding

Irish Research Council for Science, Engineering and Technology · Science Foundation Ireland

References (69)

Show source-provided references
1. The epidemiology of low back pain10.1016/j.berh.2010.10.002 ↗
3. Clinical experience in cell-based therapeutics: Disc chondrocyte transplantation a treatment for degenerated or damaged intervertebral disc10.1016/j.bioeng.2006.07.002 ↗
4. Adequacy of herniated disc tissue as a cell source for nucleus pulposus regeneration10.3171/2010.10.SPINE10223 ↗
5. Biological repair of the degenerated intervertebral disc by the injection of growth factors10.1007/s00586-008-0749-z ↗
6. Prospective randomized study of cervical arthroplasty and anterior cervical discectomy and fusion with long-term follow-up: Results in 74 patients from a single site10.3171/2012.9.SPINE12555 ↗
7. Porcine intervertebral disc repair using allogeneic juvenile articular chondrocytes or mesenchymal stem cells10.1089/ten.tea.2011.0229 ↗
8. Cell transplantation in lumbar spine disc degeneration disease10.1007/s00586-008-0750-6 ↗
9. Structured coculture of mesenchymal stem cells and disc cells enhances differentiation and proliferation10.1159/000332985 ↗
10. Transplantation of mesenchymal stem cells and nucleus pulposus cells in a degenerative disc model in rabbits: A comparison of 2 cell types as potential candidates for disc regeneration10.3171/2010.11.SPINE10285 ↗
11. Methods to monitor distribution and metabolic activity of mesenchymal stem cells following in vivo injection into nucleotomized porcine intervertebral discs10.1007/s00586-009-1255-7 ↗
12. Matrix-assisted cell transfer for intervertebral disc cell therapy10.1016/j.bbrc.2005.04.034 ↗
13. Injectable microcryogels reinforced alginate encapsulation of mesenchymal stromal cells for leak-proof delivery and alleviation of canine disc degeneration10.1016/j.biomaterials.2015.04.029 ↗
14. Cell microencapsulation technology: Towards clinical application10.1016/j.jconrel.2008.08.010 ↗
15. Designing alginate hydrogels to maintain viability of immobilized cells10.1016/S0142-9612(03)00295-3 ↗
16. Differential response of encapsulated nucleus pulposus and bone marrow stem cells in isolation and coculture in alginate and chitosan hydrogels10.1089/ten.tea.2013.0719 ↗
17. Collagen-mimetic peptide-modifiable hydrogels for articular cartilage regeneration10.1016/j.biomaterials.2015.02.079 ↗
18. Composite core-and-skirt collagen hydrogels with differential degradation for corneal therapeutic applications10.1016/j.biomaterials.2016.01.004 ↗
19. Long-term stable fibrin gels for cartilage engineering10.1016/j.biomaterials.2006.08.027 ↗
20. In vitro characterization and in vivo behavior of human nucleus pulposus and annulus fibrosus cells in clinical-grade fibrin and collagen-enriched fibrin gels10.1089/ten.tea.2014.0279 ↗
21. Alginate hydrogels as synthetic extracellular matrix materials10.1016/S0142-9612(98)00107-0 ↗
22. Microstructured dextran hydrogels for burst-free sustained release of pegylated protein drugs10.1016/j.biomaterials.2015.06.008 ↗
23. 3d bioprinting of neural stem cell-laden thermoresponsive biodegradable polyurethane hydrogel and potential in central nervous system repair10.1016/j.biomaterials.2015.08.028 ↗
24. Fibrous protein-based hydrogels for cell encapsulation10.1016/j.biomaterials.2014.04.078 ↗
25. Injectable hydrogels with in situ double network formation enhance retention of transplanted stem cells10.1002/adfm.201403631 ↗
26. Eyrich, D., Göpferich, A., and Blunk, T. (2006). Fibrin in tissue engineering. Tissue Engineering, Springer.
27. Fibrin sealants and glues10.1046/j.0886-0440.2003.02073.x ↗
28. Clinical applications of fibrin sealants10.1016/j.joms.2003.01.005 ↗
29. A biodegradable fibrin scaffold for mesenchymal stem cell transplantation10.1016/S0142-9612(02)00618-X ↗
30. Behavior of human dermal fibroblasts in three-dimensional fibrin clots: Dependence on fibrinogen and thrombin concentration10.1089/1076327041348392 ↗
31. Migration pattern, morphology and viability of cells suspended in or sealed with fibrin glue: A histomorphologic study10.1016/j.tice.2005.05.004 ↗
32. Cell proliferation on fibrin: Modulation by fibrinopeptide cleavage10.1182/blood.V86.5.1802.bloodjournal8651802 ↗
33. Chondrocyte behavior in fibrin glue in vitro10.3109/17453679308993663 ↗
34. Biomimetic fibrin-hyaluronan hydrogels for nucleus pulposus regeneration10.2217/rme.14.5 ↗
35. Human intervertebral disc cell culture for disc disorders10.1097/00003086-200402000-00039 ↗
36. Engineering of polymer-based grafts with cells derived from human nucleus pulposus tissue of the lumbar spine10.1002/term.312 ↗
37. Cultivation of porcine cells from the nucleus pulposus in a fibrin/hyaluronic acid matrix10.1080/000164700317381207 ↗
38. Inflammatory response of intervertebral disc cells is reduced by fibrin sealant scaffold in vitro10.1002/term.1503 ↗
39. Dynamic compression of chondrocyte-seeded fibrin gels: Effects on matrix accumulation and mechanical stiffness10.1016/j.joca.2003.08.009 ↗
40. The behavior of human mesenchymal stem cells in 3d fibrin clots: Dependence on fibrinogen concentration and clot structure10.1089/ten.2006.12.1587 ↗
41. Influence of thrombin concentration on the mechanical and morphological properties of cell-seeded fibrin hydrogels10.1016/j.actbio.2006.08.006 ↗
42. Fibrin microbeads loaded with mesenchymal cells support their long-term survival while sealed at room temperature10.1089/ten.tec.2010.0644 ↗
43. Influence of different commercial scaffolds on the in vitro differentiation of human mesenchymal stem cells to nucleus pulposus-like cells10.1007/s00586-011-1975-3 ↗
44. Hyaluronic acid based scaffolds for tissue engineering—A review10.1016/j.carbpol.2012.10.028 ↗
45. Kotlarchyk, M.A., Shreim, S.G., Alvarez-Elizondo, M.B., Estrada, L.C., Singh, R., Valdevit, L., Kniazeva, E., Gratton, E., Putnam, A.J., and Botvinick, E.L. (2011). Concentration independent modulation of local micromechanics in a fibrin gel. PLoS ONE, 6.10.1364/OTA.2011.OTMC6 ↗
46. Modulation of 3d fibrin matrix stiffness by intrinsic fibrinogen-thrombin compositions and by extrinsic cellular activity10.1089/ten.tea.2008.0319 ↗
47. Permeability of three-dimensional fibrin constructs corresponds to fibrinogen and thrombin concentrations10.1089/biores.2012.0211 ↗
48. Biomolecular characterization of cd44-fibrin(ogen) binding: Distinct molecular requirements mediate binding of standard and variant isoforms of cd44 to immobilized fibrin(ogen)10.1074/jbc.M805144200 ↗
49. The dual role of cd44 as a functional p-selectin ligand and fibrin receptor in colon carcinoma cell adhesion10.1152/ajpcell.00463.2007 ↗
50. Internalization of the hyaluronan receptor cd44 by chondrocytes10.1006/excr.1999.4641 ↗
51. Increased expression of cd44 in bovine articular chondrocytes by catabolic cellular mediators10.1074/jbc.270.46.27734 ↗
52. Msc surface markers (cd44, cd73, and cd90) can identify human msc-derived extracellular vesicles by conventional flow cytometry10.1186/s12964-015-0124-8 ↗
53. Cd44, hyaluronan, the hematopoietic stem cell, and leukemia-initiating cells
54. Hyaluronan and cd44: Modulators of chondrocyte metabolism10.1097/01.blo.0000143804.26638.82 ↗
55. Mechanisms regulating the binding activity of cd44 to hyaluronic acid10.2741/A307 ↗
56. Physical characteristics of hyaluronate binding to the surface of simian virus 40-transformed 3t3 cells10.1016/S0021-9258(19)85527-8 ↗
57. Affinity and distribution of surface and intracellular hyaluronic acid receptors in isolated rat liver endothelial cells10.1016/S0021-9258(18)37441-6 ↗
58. Hyaluronan binding by cell surface cd4410.1016/S0021-9258(19)61467-5 ↗
59. A comparative study on collagen type i and hyaluronic acid dependent cell behavior for osteochondral tissue bioprinting10.1088/1758-5082/6/3/035004 ↗
60. Integrin-mediated adhesion of human articular chondrocytes to cartilage10.1002/art.10704 ↗
61. Fibrin binds to collagen and provides a bridge for alphavbeta3 integrin-dependent contraction of collagen gels10.1042/BJ20140201 ↗
62. Rowe, S.L., and Institute, R.P. (2007). Mechanical Characterization of Collagen-Fibrin Composites for Vascular Tissue Engineering, Rensselaer Polytechnic Institute.
63. Stegemann, J.P., Cummings, C.L., Gawlitta, D., and Nerem, R.M. (2002, January 23–26). Collagen, fibrin and collagen-fibrin mixtures as matrix materials for vascular tissue engineering. Proceedings of the Second Joint 24th Annual Conference and the Annual Fall Meeting of the Biomedical Engineering Society] [Engineering in Medicine and Biology, Houston, TX, USA.
64. Quantitative proteomic analysis of normal and degenerated human intervertebral disc10.1016/j.spinee.2016.03.051 ↗
65. Alginate-hyaluronic acid-collagen composite hydrogel favorable for the culture of chondrocytes and their phenotype maintenance10.1007/s13770-016-0059-1 ↗
66. The effects of hyaluronic acid on articular chondrocytes10.1302/0301-620X.87B8.15083 ↗
67. Retention of hyaluronic acid in alginate beads: Aspects for in vitro cartilage engineering10.1002/(SICI)1097-4636(199902)44:2<149::AID-JBM4>3.0.CO;2-C ↗
68. Biochemical methods for the analysis of tissue-engineered cartilage
69. Determination of hydroxyproline in tissues and the evaluation of the collagen content of the tissues10.1134/S106193480701011X ↗