Evaluation of a thiol-modified hyaluronan and elastin-like polypeptide hydrogel for nucleus pulposus tissue engineering
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Degenerative disc disease (DDD) is a common medical issue among human adults, leading to back pain and potentially, disability, decreasing an individual’s quality of life. In the United States alone, huge economic impacts are apparent with an estimated $50- 100 billion attributed to lost productivity and medical costs related to DDD. Spinal degeneration occurs in the intervertebral disc (IVD) and once damaged, the IVD is incapable of adequate self-repair. A regenerative therapy incorporating nucleus pulposus (NP) tissue engineering may provide an answer to spinal degeneration. The objective of this in vitro study was to evaluate the potential of a thiol-modified hyaluronan (TMHA) and elastin-like polypeptide (ELP) as a hydrogel scaffold for nucleus pulposus tissue engineering. Two materials, one composed of TMHA only and one a 3:1 TMHA/ELP, crosslinked with polyethylene glycol diacrylate (PEGDA), were seeded with cultured human NP cells and cyclic hydrostatic loading was applied at 1MPa for 3 hours a day for 3 consecutive days. Cell viability and gene expression were analyzed. A decreasing trend in cell viability with time and cyclic hydrostatic pressure loading was observed and statistically significant differences were observed between the TMHA unloaded treatment group at day 0 and the TMHA loaded treatment group at day 4 and between the TMHA unloaded treatment group at day 0 and the 3:1 TMHA/ELP loaded group at day 4. Comparisons between TMHA only and 3:1 TMHA/ELP hydrogels for the same treatment indicate similar trends and no statistically significant differences in biological effects were observed. Gene expression analysis indicated low frequency expression of NP extracellular matrix (ECM) molecules regardless of time point or cyclic hydrostatic pressure application. These results are revealing in that the 3:1 TMHA/ELP hydrogel did not support NP cells significantly better than the TMHA hydrogel, though cell source and hydrostatic pressure generation issues may have impacted this finding. Additional studies with alternative cell type and a refined hydrostatic pressure application method may better illuminate the efficacy of a 3:1 TMHA/ELP hydrogel as for NP tissue engineering.