Characterization of biomaterials intended for use in the nucleus pulposus of degenerated intervertebral discs

Schmitz, Tara C.; Salzer, Elias; Crispim, João; Fabra, Georgina Targa; Visage, Catherine Le; Pandit, Abhay; Tryfonidou, Marianna A.; Maitre, Christine Le; Ito, Keita

doi:10.1016/j.actbio.2020.08.001

Cited by 44 publications

(61 citation statements)

References 198 publications

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“…7,15,24,25 Biomaterial and tissue engineering strategies for the IVD have been sought as a method to restore characteristics of the native tissues' structure and function. 29,30 A large body of work has demonstrated an ability to functionalize polymers with bio-adhesive ligands which are often either full-length extracellular matrix proteins, or else, small peptide sequences derived from a constituent of the extracellular matrix. [31][32][33][34][35][36][37] These approaches offer the opportunity to engineer bioactive materials that promote cell attachment and modulate cell behaviors.…”

Section: Introductionmentioning

confidence: 99%

“…[31][32][33][34][35][36][37] These approaches offer the opportunity to engineer bioactive materials that promote cell attachment and modulate cell behaviors. 29,38 While fulllength proteins and short peptides have both been utilized for this purpose, the incorporation of peptides in biomaterial design has several advantages over full-length proteins -short peptides possess increased stability and can be more economic. 39,40 Additionally, small peptide sequences offer the ability to provide controlled sites of biomaterialcell interactions.…”

Section: Introductionmentioning

confidence: 99%

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

Speer

Barcellona

et al. 2021

J Tissue Eng

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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.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Speer

Barcellona

et al. 2021

J Tissue Eng

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“…Changes have also been observed in the presence of matrix degrading enzymes such as the MMP and ADAMTS families, which results in an altered cellular microenvironment and a decreased ability for tissue repair and homeostasis 4,[15][16][17] . As the NP has limited ability for self-repair, biomaterials have been investigated as a means to deliver cells to the degenerative disc or to provide stimuli to modulate cell (endogenous or exogenous) behavior and promote IVD regeneration 14,18,19 .…”

Section: Introductionmentioning

confidence: 99%

“…The mechanobiological cues cells encounter in their environment have the ability to regulate cell behaviors (including cell signaling, biosynthesis, and motility), phenotype, and global transcriptomic changes [20][21][22][23] . Biomaterial strategies have utilized natural and/or synthetic materials functionalized with bioactive moieties such as full-length proteins or peptide sequences in order to promote tissue repair or cell differentiation 19,[24][25][26] . In addition to ligand presentation, other biomaterial parameters including substrate stiffness, porosity, topography, and surface chemistry have been tested for their ability to modulate cell behaviors 27-33 .…”

Section: Introductionmentioning

confidence: 99%

“…In addition to ligand presentation, other biomaterial parameters including substrate stiffness, porosity, topography, and surface chemistry have been tested for their ability to modulate cell behaviors 27-33 . 14,20,34-37 Previous studies have shown that culture of NP cells upon soft (~0.5 kPa) hydrogel substrates functionalized with laminin-111 can be used to promote the cell behaviors and gene expression profiles characteristically observed in the juvenile NP, while cells cultured on stiff (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) hydrogel substrates or tissue culture plastic exhibit a fibroblast-like phenotype 9,38,39 . While this work made use of full-length laminin proteins, short peptide sequences offers several advantages in biomaterial design including the opportunity to precisely control sites of biomaterial and cell interactions 24,39 .…”

Section: Introductionmentioning

confidence: 99%

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Engineered Peptide-Functionalized Hydrogels Modulate the RNA Transcriptome of Human Nucleus Pulposus Cells In Vitro

Barcellona

Speer

Jing

et al. 2021

Preprint

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Degeneration and aging of the nucleus pulposus (NP) of the intervertebral disc (IVD) is accompanied by alterations in NP cell phenotype marked by a shift towards a fibroblast-like, catabolic state. We have recently demonstrated an ability to manipulate the phenotype of human adult degenerative NP cells through 2D culture upon poly(ethylene glycol) (PEG) based hydrogels dually functionalized with integrin- and syndecan-binding laminin-mimetic peptides (LMPs). In the present study, we sought to understand the transcriptomic changes elicited through NP cell interactions with the LMP-functionalized hydrogel system (LMP gel) by examining targets of interest a priori and by conducting unbiased analysis to identify novel mechanosensitive targets. The results of gene specific analysis demonstrated that the LMP gel promoted adult degenerative NP cells to upregulate 148 genes including several NP markers (e.g. NOG and ITGA6) and downregulate 277 genes, namely several known fibroblastic markers. Additionally, 13 genes associated with G protein-coupled receptors, many of which are known drug targets, were identified as differentially regulated following culture upon the gel. Furthermore, through gene set enrichment analysis we identified over 700 pathways enriched amongst the up- and downregulated genes including pathways related to cell differentiation, notochord morphogenesis, and intracellular signaling. Together these findings demonstrate the global mechanobiological effects induced by the LMP gel and confirm the ability of this substrate to modulate NP cell phenotype.

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Injectable and Microporous Microgel Assembly with Sequential Bioactive Factor Release for the Endogenous Repair of Nucleus Pulposus

Luo,

Wang,

et al. 2024

Adv Funct Materials

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Harnessing endogenous stem/progenitor cells to enhance extracellular matrix (ECM) deposition in the nucleus pulposus (NP) is considered as a potential treatment for intervertebral disc degeneration (IVDD), but is limited by the lack of suitable scaffolds for cell infiltration and growth, as well as the tailored release of bioactive factors. Herein, an injectable cell‐free microgel assembly (MA‐TNS) with interconnected microporous structure is developed to recruit stem/progenitor cells and induce the differentiation of the recruited cells by releasing stromal cell‐derived factor‐1α (SDF‐1α) and transforming growth factor‐β1 (TGF‐β1) sequentially. TGF‐β1 is initially loaded by the chondroitin sulfate/gelatin nanoparticles. Together with SDF‐1α, these nanoparticles are co‐encapsulated into the photo‐cross‐linked microgels, which are then assembled into a microporous scaffold via dynamic boronate ester bonds. An initial rapid release of SDF‐1α followed by a sustained release of TGF‐β1 lasting over 28 days is achieved. MA‐TNS significantly promotes the recruitment, infiltration, and chondrocyte‐like differentiation of marrow mesenchymal stem cells in vitro. Furthermore, in vivo experiments on rats and cynomolgus monkeys prove that MA‐TNS can inhibit IVDD and recover ECM deposition markedly, thereby enabling long‐term NP reconstruction. The resulting efficacy in rats and nonhuman primates supports that MA‐TNS is a promising scaffold for intervertebral disc repair and regeneration.

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Characterization of biomaterials intended for use in the nucleus pulposus of degenerated intervertebral discs

Cited by 44 publications

References 198 publications

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

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

Engineered Peptide-Functionalized Hydrogels Modulate the RNA Transcriptome of Human Nucleus Pulposus Cells In Vitro

Injectable and Microporous Microgel Assembly with Sequential Bioactive Factor Release for the Endogenous Repair of Nucleus Pulposus

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