Fibronectin Peptide Modified Hydrogels Activate a Contractile Phenotype in Nucleus Pulposus Cells.

Abstract

Degenerative disc disease is strongly associated with low back pain, making it a leading cause of disability. With injury and age, cellular remodeling of the disc tissue leads to compositional changes, stiffening, and loss of stress relaxation, particularly in the central gelatinous nucleus pulposus (NP) region of the disc. As part of this extracellular matrix (ECM) remodeling, there is an increase in the deposition of fibronectin, a strongly adhesive integrin ligand that is known to regulate inflammatory signaling. However, it is unclear how these pathological changes in cellular adhesion regulate cell phenotype, and which domains of fibronectin are specifically involved. Here, a dextran vinyl sulfone (DexVS) hydrogel system is employed for presentation of specific fibronectin domains. Fibronectin peptides are found to enhance YAP signaling, inflammatory NF-κB signaling, cellular adhesion, and cellular contractility in NP cells, which leads to a decrease in aggrecan gene expression. Covalent modification of these DexVS hydrogels with bioactive peptides allows for targeted interactions with specific integrin receptors that are involved in healthy or degenerative signaling. In doing so, the integrin binding peptides from fibronectin are identified to activate a contractile phenotype in NP cells.