@article{198d9b0e5ad34b15b0ae8e415485dcc4,
title = "Integrin and syndecan binding peptide-conjugated alginate hydrogel for modulation of nucleus pulposus cell phenotype",
abstract = "Biomaterial based strategies have been widely explored to preserve and restore the juvenile phenotype of cells of the nucleus pulposus (NP) in degenerated intervertebral discs (IVD). With aging and maturation, NP cells lose their ability to produce necessary extracellular matrix and proteoglycans, accelerating disc degeneration. Previous studies have shown that integrin or syndecan binding peptide motifs from laminin can induce NP cells from degenerative human discs to re-express juvenile NP-specific cell phenotype and biosynthetic activity. Here, we engineered alginate hydrogels to present integrin- and syndecan-binding peptides alone or in combination (cyclic RGD and AG73, respectively) to introduce bioactive features into the alginate gels. We demonstrated human NP cells cultured upon and within alginate hydrogels presented with cRGD and AG73 peptides exhibited higher cell viability, biosynthetic activity, and NP-specific protein expression over alginate alone. Moreover, the combination of the two peptide motifs elicited markers of the NP-specific cell phenotype, including N-Cadherin, despite differences in cell morphology and multicellular cluster formation between 2D and 3D cultures. These results represent a promising step toward understanding how distinct adhesive peptides can be combined to guide NP cell fate. In the future, these insights may be useful to rationally design hydrogels for NP cell-transplantation based therapies for IVD degeneration.",
keywords = "Cell therapy, Disc degeneration, Intervertebral disc, Laminin-mimetic peptides, Ligand presentation, Microenvironment",
author = "Xiaohong Tan and Era Jain and Barcellona, {Marcos N.} and Evan Morris and Sydney Neal and Gupta, {Munish C.} and Buchowski, {Jacob M.} and Michael Kelly and Setton, {Lori A.} and Nathaniel Huebsch",
note = "Funding Information: This material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. DGE-1745038 and DGE-2139839. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. This work was further supported by the Department of Biomedical Engineering at Washington University in Saint Louis. We thank Dr. Chris Madl (Stanford University) for helpful advice regarding Maleimide-Thiol click chemistry, and Barbara Semar (Washington University in St. Louis, Department of Mechanical Engineering and Materials Science) for help with the TA ElectroForce 3200 instrument for mechanical testing. Funding Information: This material is based upon work supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. DGE-1745038 and DGE-2139839 . Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation . This work was further supported by the Department of Biomedical Engineering at Washington University in Saint Louis . We thank Dr. Chris Madl (Stanford University) for helpful advice regarding Maleimide-Thiol click chemistry, and Barbara Semar (Washington University in St. Louis, Department of Mechanical Engineering and Materials Science) for help with the TA ElectroForce 3200 instrument for mechanical testing. Publisher Copyright: {\textcopyright} 2021",
year = "2021",
month = oct,
doi = "10.1016/j.biomaterials.2021.121113",
language = "English",
volume = "277",
journal = "Biomaterials",
issn = "0142-9612",
}