Tissue Engineering Strategies for Intervertebral Disc Treatment Using Functional Polymers

Choi, Youngjoo; Park, Min Hee; Lee, Kangwon

doi:10.3390/polym11050872

Cited by 40 publications

(41 citation statements)

References 224 publications

(281 reference statements)

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“…[26][27][28][29][30][31][32][33] Literature similarly supports that NP cells are mechanosensitive in vitro and in vivo, and as such, many groups have developed biomaterials designed to control the phenotype and behaviors of NP cells. 7,[34][35][36][37][38][39][40][41][42] Much of this work consistently shows that NP cell morphology responds to both ligand and stiffness, where soft, laminin-presenting substrates promote a juvenile, healthy rounded morphology, but stiff and/or non-laminin associated ligands allow a spread, fibroblastic-like shape observed in adult NP. 7,15,37,[42][43][44][45][46][47][48] These reports also support the idea that changes in NP cell shape are associated with concomitant increases in expression of phenotypic markers and matrix biosynthesis.…”

mentioning

confidence: 72%

Verteporfin treatment controls morphology, phenotype, and global gene expression for cells of the human nucleus pulposus

et al. 2020

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Cells of the nucleus pulposus (NP) are essential contributors to extracellular matrix synthesis and function of the intervertebral disc. With age and degeneration, the NP becomes stiffer and more dehydrated, which is associated with a loss of phenotype and biosynthetic function for its resident NP cells. Also, with aging, the NP cell undergoes substantial morphological changes from a rounded shape with pronounced vacuoles in the neonate and juvenile, to one that is more flattened and spread with a loss of vacuoles. Here, we make use of the clinically relevant pharmacological treatment verteporfin (VP), previously identified as a disruptor of yes-associated protein-TEA domain family member-binding domain (TEAD) signaling, to promote morphological changes in adult human NP cells in order to study variations in gene expression related to differences in cell shape. Treatment of adult, degenerative human NP cells with VP caused a shift in morphology from a spread, fibroblastic-like shape to a rounded, clustered morphology with decreased transcriptional activity of TEAD and serum-response factor. These changes were accompanied by an increased expression of vacuoles, NP-specific gene markers, and biosynthetic activity. The contemporaneous observation of VP-induced

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confidence: 72%

Verteporfin treatment controls morphology, phenotype, and global gene expression for cells of the human nucleus pulposus

et al. 2020

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“…Biomaterials serve a fundamental role in tissue engineering (TE) by acting as scaffolds for in situ tissue replenishment as well as being carriers for cells and biological molecules. A number of review articles provide summaries of the numerous and varied biomaterials suitable for the IVD [ 358 , 359 , 360 ]. Often, the biomechanics of the native tissue is replicated as closely as possible with the design of the biomaterial, along with the ability to encourage adherence, growth, and/or differentiation of cells.…”

Section: Ivd Regeneration Strategies: Biological Targets and Biomamentioning

confidence: 99%

Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research

Baumgartner

Wuertz‐Kozak

Maitre

et al. 2021

IJMS

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Intervertebral disc (IVD) degeneration is a major risk factor of low back pain. It is defined by a progressive loss of the IVD structure and functionality, leading to severe impairments with restricted treatment options due to the highly demanding mechanical exposure of the IVD. Degenerative changes in the IVD usually increase with age but at an accelerated rate in some individuals. To understand the initiation and progression of this disease, it is crucial to identify key top-down and bottom-up regulations’ processes, across the cell, tissue, and organ levels, in health and disease. Owing to unremitting investigation of experimental research, the comprehension of detailed cell signaling pathways and their effect on matrix turnover significantly rose. Likewise, in silico research substantially contributed to a holistic understanding of spatiotemporal effects and complex, multifactorial interactions within the IVD. Together with important achievements in the research of biomaterials, manifold promising approaches for regenerative treatment options were presented over the last years. This review provides an integrative analysis of the current knowledge about (1) the multiscale function and regulation of the IVD in health and disease, (2) the possible regenerative strategies, and (3) the in silico models that shall eventually support the development of advanced therapies.

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“…HA is a high molecular weight-nonsulfated GAG which is normally expressed within the healthy IVD matrix. Such molecule is fundamental in multiple biological processes, including cell migration, survival, apoptosis, and morphogenesis as well as tumorigenesis and tissue inflammation [138]. For these reasons, HA is being widely investigated as a bioscaffold in IVD regeneration in various formulations.…”

Section: Under Inflammatory Conditions Adscs Have Beenmentioning

confidence: 99%

Interaction between Mesenchymal Stem Cells and Intervertebral Disc Microenvironment: From Cell Therapy to Tissue Engineering

Vadalà

Ambrosio

Russo

et al. 2019

Stem Cells International

112

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Low back pain (LBP) in one of the most disabling symptoms affecting nearly 80% of the population worldwide. Its primary cause seems to be intervertebral disc degeneration (IDD): a chronic and progressive process characterized by loss of viable cells and extracellular matrix (ECM) breakdown within the intervertebral disc (IVD) especially in its inner region, the nucleus pulposus (NP). Over the last decades, innovative biological treatments have been investigated in order to restore the original healthy IVD environment and achieve disc regeneration. Mesenchymal stem cells (MSCs) have been widely exploited in regenerative medicine for their capacity to be easily harvested and be able to differentiate along the osteogenic, chondrogenic, and adipogenic lineages and to secrete a wide range of trophic factors that promote tissue homeostasis along with immunomodulation and anti-inflammation. Several in vitro and preclinical studies have demonstrated that MSCs are able to acquire a NP cell-like phenotype and to synthesize structural components of the ECM as well as trophic and anti-inflammatory mediators that may support resident cell activity. However, due to its unique anatomical location and function, the IVD presents distinctive features: avascularity, hypoxia, low glucose concentration, low pH, hyperosmolarity, and mechanical loading. Such conditions establish a hostile microenvironment for both resident and exogenously administered cells, which limited the efficacy of intradiscal cell therapy in diverse investigations. This review is aimed at describing the characteristics of the healthy and degenerated IVD microenvironment and how such features influence both resident cells and MSC viability and biological activity. Furthermore, we focused on how recent research has tried to overcome the obstacles coming from the IVD microenvironment by developing innovative cell therapies and functionalized bioscaffolds.

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Tissue Engineering Strategies for Intervertebral Disc Treatment Using Functional Polymers

Cited by 40 publications

References 224 publications

Verteporfin treatment controls morphology, phenotype, and global gene expression for cells of the human nucleus pulposus

Verteporfin treatment controls morphology, phenotype, and global gene expression for cells of the human nucleus pulposus

Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research

Interaction between Mesenchymal Stem Cells and Intervertebral Disc Microenvironment: From Cell Therapy to Tissue Engineering

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