An interpenetrating network-strengthened and toughened hydrogel that supports cell-based nucleus pulposus regeneration

Ye, Gan; Li, Pei; Wang, Liyuan; Mo, Xiumei; Song, Lei; Xu, Yuan; Zhao, Chen; Ouyang, Bo; Tu, Bing; Luo, Lei; Zhu, Linyong; Dong, Shiwu; Li, Fuyou; Zhou, Qiang

doi:10.1016/j.biomaterials.2017.05.017

Cited by 99 publications

(77 citation statements)

References 68 publications

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“…In the study, we constructed the 3D culture system for MSCs by using an IPN hydrogel as scaffold. Our previous study has shown that the IPN hydrogel is tough enough to resist the extremely high magnitude of compression without structural failure [ 14 ]. Meanwhile, it exhibited as friendly to the encapsulated cell for long-term culture.…”

Section: Discussionmentioning

confidence: 99%

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Low Magnitude of Compression Enhances Biosynthesis of Mesenchymal Stem Cells towards Nucleus Pulposus Cells via the TRPV4-Dependent Pathway

et al. 2018

Stem Cells International

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Mesenchymal stem cell- (MSC-) based therapy is regarded as a promising tissue engineering strategy to achieve nucleus pulposus (NP) regeneration for the treatment of intervertebral disc degeneration (IDD). However, it is still a challenge to promote the biosynthesis of MSC to meet the requirement of NP regeneration. The purpose of this study was to optimize the compressive magnitude to enhance the extracellular matrix (ECM) deposition towards discogenesis of MSCs. Thus, we constructed a 3D culture model for MSCs to bear different magnitudes of compression for 7 days (5%, 10%, and 20% at the frequency of 1.0 Hz for 8 hours/day) using an intelligent and mechanically active bioreactor. Then, the underlying mechanotransduction mechanism of transient receptor potential vanilloid 4 (TRPV4) was further explored. The MSC-encapsulated hybrids were evaluated by Live/Dead staining, biochemical content assay, real-time PCR, Western blot, histological, and immunohistochemical analysis. The results showed that low-magnitude compression promoted anabolic response where high-magnitude compression induced the catabolic response for the 3D-cultured MSCs. The anabolic effect of low-magnitude compression could be inhibited by inhibiting TRPV4. Meanwhile, the activation of TRPV4 enhanced the biosynthesis analogous to low-magnitude compression. These findings demonstrate that low-magnitude compression promoted the anabolic response of ECM deposition towards discogenesis for the 3D-cultured MSCs and the TRPV4 channel plays a key role on mechanical signal transduction for low-magnitude compressive loading. Further understanding of this mechanism may provide insights into the development of new therapies for MSC-based NP regeneration.

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Section: Discussionmentioning

confidence: 99%

“…Finally, the mixture was lyophilized and cryopreserved. The IPN hydrogels were prepared as previously described [ 14 ]. Briefly, dextran, gelatin, and PEG solutions in PBS were mixed as the mass ratio of 5 : 3 : 2 to achieve a final polymer concentration of 10% while I2959 (Sigma-Aldrich, USA) concentration was 0.1%.…”

Section: Methodsmentioning

confidence: 99%

Low Magnitude of Compression Enhances Biosynthesis of Mesenchymal Stem Cells towards Nucleus Pulposus Cells via the TRPV4-Dependent Pathway

et al. 2018

Stem Cells International

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“…However, in the 3D culture system, most of the scaffolds may provide the microenvironment to support cell proliferation and differentiation (Braunger et al, 2017;Hao et al, 2017), and thus benefit NP cell engineering (Gan et al, 2017;Y. Zhu et al, 2017), which is not appropriate to use as a degenerative NP cell models.…”

Section: Discussionmentioning

confidence: 99%

Andrographolide prevents human nucleus pulposus cells against degeneration by inhibiting the NF‐κB pathway

Liu

Jiang

et al. 2018

Journal Cellular Physiology

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Intervertebral disc degeneration (IDD) is among the most common spinal disorders, pathologically characterized by excessive cell apoptosis and production of proinflammatory factors. Pharmacological targeting of nucleus pulposus (NP) degeneration may hold promise in IDD therapy, but it is limited by adverse side effects and nonspecificity of drugs. In this study, we used a natural compound, andrographolide (ANDRO), which has been widely used to intervene inflammatory and apoptotic diseases in the investigation of NP degeneration based on IDD‐patients‐derived NP cells by lipopolysaccharide (LPS) treatment for the preservation of degeneration. The results showed that LPS maintained the degeneration status of NP cells as evidenced by a high apoptosis rate and the expression of degenerative and inflammatory mediators after LPS treatment. ANDRO reversed the effects of LPS‐caused degeneration of NP cells and maintained the phenotype of NP cells, as demonstrated by flow cytometry, degenerative mediators (ADAMTS4 and ADAMTS5), inflammatory factors (COX2, PGE2, MMP‐13, and MMP‐3), biomarkers of NP cells (SOX9, ACAN, and COL2A1) expressions, and glycosaminoglycan secretion. We also found the involvement of the nuclear factor kappa‐light‐chain‐enhancer of the activated B cells (NF‐κB) pathway in ANDRO treatment, indicating that ANDRO prevented the LPS‐preserved degeneration of NP cells by inhibiting the NF‐κB pathway. This study may provide a reference for clinic medication of IDD therapy.

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“…Gan et al [386] studied the interpenetration between a primary network made of dextran and gelatin and a secondary network composed of PEG. The resulted hybrid hydrogels exhibited improved toughness and good proliferation, clustering and adhesion of the incorporated nucleus pulposus cells, when the proportion of the natural network was 4-fold greater than the synthetic one.…”

Section: Bone Tissue Engineeringmentioning

confidence: 99%

New Developments in Medical Applications of Hybrid Hydrogels Containing Natural Polymers

Vasile¹,

Pamfil²,

Stoleru³

et al. 2020

Molecules

210

131

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New trends in biomedical applications of the hybrid polymeric hydrogels, obtained by combining natural polymers with synthetic ones, have been reviewed. Homopolysaccharides, heteropolysaccharides, as well as polypeptides, proteins and nucleic acids, are presented from the point of view of their ability to form hydrogels with synthetic polymers, the preparation procedures for polymeric organic hybrid hydrogels, general physico-chemical properties and main biomedical applications (i.e., tissue engineering, wound dressing, drug delivery, etc.).

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An interpenetrating network-strengthened and toughened hydrogel that supports cell-based nucleus pulposus regeneration

Cited by 99 publications

References 68 publications

Low Magnitude of Compression Enhances Biosynthesis of Mesenchymal Stem Cells towards Nucleus Pulposus Cells via the TRPV4-Dependent Pathway

Low Magnitude of Compression Enhances Biosynthesis of Mesenchymal Stem Cells towards Nucleus Pulposus Cells via the TRPV4-Dependent Pathway

Andrographolide prevents human nucleus pulposus cells against degeneration by inhibiting the NF‐κB pathway

New Developments in Medical Applications of Hybrid Hydrogels Containing Natural Polymers

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