Advances in biological therapy for nucleus pulposus regeneration

Priyadarshani, Priyanka; Li, Yongchao; Yao, Li

doi:10.1016/j.joca.2015.08.014

Cited by 103 publications

(75 citation statements)

References 87 publications

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“…It is well established that biological therapies for disc degeneration are better able to restore normal disc function than previous traditional treatments [2]. Importantly, the normal biological function of NP cells (i.e., matrix biosynthesis) is important for the efficacy of the tissue-engineered NP tissue in regenerating disc degeneration [40]. In the present study, we demonstrated that dynamic compression is more beneficial than static compression to increase the matrix synthesis of NP cells and that the N-CDH-PI3K/Akt pathway is involved in this regulatory process.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Compression Promotes the Matrix Synthesis of Nucleus Pulposus Cells Through Up-Regulating N-CDH Expression in a Perfusion Bioreactor Culture

Yao

et al. 2018

Cell Physiol Biochem

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Background/Aims: An adequate matrix production of nucleus pulposus (NP) cells is an important tissue engineering-based strategy to regenerate degenerative discs. Here, we mainly aimed to investigate the effects and mechanism of mechanical compression (i.e., static compression vs. dynamic compression) on the matrix synthesis of three-dimensional (3D) cultured NP cells in vitro. Methods: Rat NP cells seeded on small intestinal submucosa (SIS) cryogel scaffolds were cultured in the chambers of a self-developed, mechanically active bioreactor for 10 days. Meanwhile, the NP cells were subjected to compression (static compression or dynamic compression at a 10% scaffold deformation) for 6 hours once per day. Unloaded NP cells were used as controls. The cellular phenotype and matrix biosynthesis of NP cells were investigated by real-time PCR and Western blotting assays. Lentivirus-mediated N-cadherin (N-CDH) knockdown and an inhibitor, LY294002, were used to further investigate the role of N-CDH and the PI3K/Akt pathway in this process. Results: Dynamic compression better maintained the expression of cell-specific markers (keratin-19, FOXF1 and PAX1) and matrix macromolecules (aggrecan and collagen II), as well as N-CDH expression and the activity of the PI3K/Akt pathway, in the 3D-cultured NP cells compared with those expression levels and activity in the cells grown under static compression. Further analysis showed that the N-CDH knockdown significantly down-regulated the expression of NP cell-specific markers and matrix macromolecules and inhibited the activation of the PI3K/Akt pathway under dynamic compression. However, inhibition of the PI3K/Akt pathway had no effects on N-CDH expression but down-regulated the expression of NP cell-specific markers and matrix macromolecules under dynamic compression. Conclusion: Dynamic compression increases the matrix synthesis of 3D-cultured NP cells compared with that of the cells under static compression, and the N-CDH-PI3K/Akt pathway is involved in this regulatory process. This study provides a promising strategy to promote the matrix deposition of tissue-engineered NP tissue in vitro prior to clinical transplantation.

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Section: Discussionmentioning

confidence: 99%

Dynamic Compression Promotes the Matrix Synthesis of Nucleus Pulposus Cells Through Up-Regulating N-CDH Expression in a Perfusion Bioreactor Culture

Yao

et al. 2018

Cell Physiol Biochem

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“…Natural hydrogels often possess good cytocompatible properties. Hence, these are frequently included in possible tissue engineering treatment approaches (Priyadarshani et al, 2015), e.g. agarose (Awad et al, 2004;Bougault et al, 2012;Iwata et al, 2013;Luo et al, 2015;Mauck et al, 2006), collagen (Borde et al, 2015;Calderon et al, 2010;Mercuri et al, 2014;Omlor et al, 2012;Tsaryk et al, 2015), alginate (Bron et al, 2011;Duggal et al, 2009;Xu et al, 2008;Zeng et al, 2015a), chitosan (Naqvi and Buckley, 2015;Ngoenkam et al, 2010), and combinations of alginate and chitosan have been investigated (Shao , 2007).…”

Section: Reinforced Hydrogels For Intervertebral Disc Tissue Engineeringmentioning

confidence: 99%

A review of the application of reinforced hydrogels and silk as biomaterials for intervertebral disc repair

Frauchiger¹,

Tekari²,

Wöltje³

et al. 2017

eCM

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The degeneration of the intervertebral disc (IVD) within the spinal column represents a major pain source for many patients. Biological restoration or repair of the IVD using "compressive-force-resistant" and at the same time "cytocompatible" materials would be desirable over current purely mechanical solutions, such as spinal fusion or IVD implants. This review provides an overview of recent research on the repair of the inner (nucleus pulposus = NP) and the outer (annulus fibrous = AF) parts of the IVD tissue. Many studies have addressed NP repair using hydrogel-like materials. However, only a few studies have so far focused on AF repair. As the AF possesses an extremely low self-healing capacity and special attention to shear-force resistance is essential, special repair designs are required. In our review, we stated the challenges in IVD repair and highlighted the use of composite materials such as silk biomaterials and fibrin cross-linked reinforced hydrogels. We elaborated on the origin of silk and its many in tissue engineering. Furthermore, techniques such as electrospinning and 3D printing technologies allow the fabrication of versatile and functionalised 3D scaffolds. We summarised the research that has been conducted in the field of regenerative medicine over the recent years, with a special focus on the potential application and the potential of combining silk and reinforced -and thus mechanically tailored -hydrogels for IVD repair.

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“…As progressive degeneration first manifests in the NP, there has been considerable interest in developing hydrogel-base strategies that can synergize with stem cells and bioactive molecules to augment and potentially restore native NP tissue [15]. A candidate hydrogel for NP regeneration would ideally be injectable (to allow for minimally invasive delivery), would rapidly solidify (to prevent extrusion from the disc space with loading), and be able to augment the mechanical function of the degenerative motion segment.…”

Section: Introductionmentioning

confidence: 99%

Translation of an injectable triple-interpenetrating-network hydrogel for intervertebral disc regeneration in a goat model

et al. 2017

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Degeneration of the intervertebral discs is a progressive cascade of cellular, compositional and structural changes that is frequently associated with low back pain. As the first signs of disc degeneration typically arise in the disc's central nucleus pulposus (NP), augmentation of the NP via hydrogel injection represents a promising strategy to treat early to mid-stage degeneration. The purpose of this study was to establish the translational feasibility of a triple interpenetrating network hydrogel composed of dextran, chitosan, and teleostean (DCT) for augmentation of the degenerative NP in a preclinical goat model. Ex vivo injection of the DCT hydrogel into degenerated goat lumbar motion segments restored range of motion and neutral zone modulus towards physiologic values. To facilitate non-invasive assessment of hydrogel delivery and distribution, zirconia nanoparticles were added to the hydrogel to make the hydrogel radiopaque. Importantly, the addition of zirconia did not negatively impact viability or matrix producing capacity of goat mesenchymal stem cells or NP cells seeded within the hydrogel in vitro. In vivo studies demonstrated that the radiopaque DCT hydrogel was successfully delivered to degenerated goat lumbar intervertebral discs, where it distributed throughout both the NP and annulus fibrosus, and that the hydrogel remained contained within the disc space for two weeks without evidence of extrusion. These results demonstrate the translational potential of this hydrogel for functional regeneration of degenerate intervertebral discs.

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Advances in biological therapy for nucleus pulposus regeneration

Abstract: Though recent studies advance the body of knowledge needed to treat degenerated discs, many challenges need to be overcome before the application of these approaches can be successful clinically.

Cited by 103 publications

References 87 publications

Dynamic Compression Promotes the Matrix Synthesis of Nucleus Pulposus Cells Through Up-Regulating N-CDH Expression in a Perfusion Bioreactor Culture

Dynamic Compression Promotes the Matrix Synthesis of Nucleus Pulposus Cells Through Up-Regulating N-CDH Expression in a Perfusion Bioreactor Culture

A review of the application of reinforced hydrogels and silk as biomaterials for intervertebral disc repair

Translation of an injectable triple-interpenetrating-network hydrogel for intervertebral disc regeneration in a goat model

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