Development of a library of laminin-mimetic peptide hydrogels for control of nucleus pulposus cell behaviors

Abstract

The nucleus pulposus (NP) of the intervertebral disc plays a critical role in distributing mechanical loads to the axial skeleton. Alterations in NP cells and, consequently, NP matrix are some of the earliest changes in the development of disc degeneration. Previous studies demonstrated a role for laminin-presenting biomaterials in promoting a healthy phenotype for human NP cells from degenerated tissue. Here we investigate the use of laminin-mimetic peptides presented individually or in combination on a poly(ethylene) glycol hydrogel as a platform to modulate the behaviors of degenerative human NP cells. Data confirm that NP cells attach to select laminin-mimetic peptides that results in cell signaling downstream of integrin and syndecan binding. Furthermore, the peptide-functionalized hydrogels demonstrate an ability to promote cell behaviors that mimic that of full-length laminins. These results identify a set of peptides that can be used to regulate NP cell behaviors toward a regenerative engineering strategy.

Intervertebral Disc Degeneration: Biomaterials and Tissue Engineering Strategies toward Precision Medicine

“…[ 75 ] Laminins are ECM glycoproteins comprise of β , α , and γ chains that regulate cell survival, adhesion, differentiation, and migration. A study reported that a series of laminin‐mimetic peptide poly(ethylene) glycol (PEG) hydrogels modulated integrin and syndecan binding in NP cells, thus promoting ECM biosynthesis [ 76 ] primarily through integrin α 3 mediated interaction with laminin, which also associated with phosphorylation of signaling molecules of extracellular‐signal‐regulated kinase (ERK1/2) and glycogen synthase kinase (GSK3 β ). [ 77 ]…”

Importance of Matrix Cues on Intervertebral Disc Development, Degeneration, and Regeneration

“…At least six integrin-and syndecan-binding peptide sequences have been developed which successfully drive healthier NP cell phenotypes [132]. The use of such systems provides the clearest indication yet that matrix cues can be used to directly modulate cell behaviours [185] and potentially mimic a combination of cues present in development, health, and degeneration. Peptide-conjugated alginate hydrogels have similarly been exploited, with cell-adhesive and syndecan-binding domains encouraging the production of NP-specific phenotypes within alginate cultures, in some instances regardless of presented cell-adhesive domains [186].…”

“…Nor are there many that combine the use of these matrix molecules with stiffness-tuneable biomaterials for mechanical cue incorporation. This has been achieved in a small number of instances for IVD, using in situ crosslinkable peptide delivery systems [244,245] and laminin-functionalised pegylated hydrogels of varying stiffnesses [185]. Such approaches are generating novel data regarding mechanotransduction, notochord morphogenesis, intracellular signalling, cell differentiation, and matrix synthesis, which are of major relevance to IVD regeneration strategies moving forward [81,132].…”

A Novel Three-Dimensional Follicle Culture System Decreases Oxidative Stress and Promotes the Prolonged Culture of Human Granulosa Cells

“…Bioadhesive ligands such as full-length proteins or short peptides have been shown to functionalize biomaterials to promote cell adhesion and modulate cell behavior. − The utilization of short peptides showed a number of apparent advantages: small peptides are more stable, cheaper, and capable of mass production . Full-length laminin proteins have multiple bioactive amino acid sequences that may lead to uncontrollable intercellular interactions . IKVAV and YIGSR are laminin-mimetic peptides located in the Laminin α1 and β1 chains, respectively.…”