Development of kartogenin-conjugated chitosan–hyaluronic acid hydrogel for nucleus pulposus regeneration

Zhu, Yanxia; Tan, Jie; Zhu, Hongxia; Lin, Gonghua; Yin, Fei; Wang, Liang; Song, Kedong; Wang, Yiwei; Zhou, Guangqian; Yi, Weihong

doi:10.1039/c7bm00001d

Cited by 64 publications

(49 citation statements)

References 33 publications

(37 reference statements)

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“…The inclusion of both KGN and TGF‐β also did not produce a synergistic effect with respect to inducing nucleus pulposus properties. Still, with further refinement, this material may offer a potentially straightforward means of repairing degenerated NP tissue after minimally invasive surgery …”

Section: Kgn and Disc Regenerationmentioning

confidence: 99%

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Application of kartogenin for musculoskeletal regeneration

2017

J Biomedical Materials Res

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Kartogenin (KGN) is a recently characterized small molecule that promotes the selective differentiation of mesenchymal stem cells into chondrocytes, and thus, KGN stimulates cartilage regeneration. KGN also possess chondro-protective effect. Furthermore, because it is a highly stable small molecule, KGN can be stored and transported at room temperature. These obvious superiorities over peptide growth factors make KGN a desirable chondrogenic agent for cartilage regeneration. Since its discovery, KGN has drawn much attention as a new chondrogenic drug for intraarticular (IA) treatment. Although it was originally developed with a focus on OA, it has been used to treat other conditions and to promote disc and bone-tendon junction regeneration. Our group has also developed several formulations for IA delivery of KGN including KGN-conjugated chitosan nano/microparticles, thermo-responsive polymeric nanospheres based on chitosan oligosaccharide conjugated pluronic F127, and hyluronate hydrogels containing polyethylene glycol (PEG/KGN) micelles. This review was undertaken to summarize current research on the action mechanism of KGN and the various formulations described in the literature that induce musculoskeletal regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1141-1148, 2018.

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Section: Kgn and Disc Regenerationmentioning

confidence: 99%

“…Still, with further refinement, this material may offer a potentially straightforward means of repairing degenerated NP tissue after minimally invasive surgery. 23…”

Section: Kgn and Disc Regenerationmentioning

confidence: 99%

Application of kartogenin for musculoskeletal regeneration

2017

J Biomedical Materials Res

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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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“…3 Stem cell-based tissue engineering is widely used in the treatment of IDD. 5 As ADSCs have the potential to differentiate into multiple cell types, the main difficulty that has arisen in utilizing ADSCs for this type of therapy has been in controlling the directional differentiation of ADSCs toward an NP-like phenotype. 5 As ADSCs have the potential to differentiate into multiple cell types, the main difficulty that has arisen in utilizing ADSCs for this type of therapy has been in controlling the directional differentiation of ADSCs toward an NP-like phenotype.…”

Section: Introductionmentioning

confidence: 99%

Genipin‐cross‐linked type II collagen scaffold promotes the differentiation of adipose‐derived stem cells into nucleus pulposus‐like cells

Zhou

Tao

Chen

et al. 2018

J Biomedical Materials Res

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Adipose-derived stem cells (ADSCs)-based tissue engineering was a promising method to treat intervertebral disc degeneration. Type II collagen is a native component in the nucleus pulposus (NP), and has the ability to promote ADSCs to differentiate into NP-like cells. In this article, we aimed to establish a genipin-cross-linked three-dimensional (3D) type II collagen scaffold, and determine the biological effects of the scaffold on ADSCs differentiating into a NP-like phenotype. Different concentrations of genipin were used to cross-link the 3D type II collagen scaffold. Microstructure, surface topography, mechanical strength, porosity, swelling property, and biological stability of the scaffolds were detected to evaluate the scaffold properties. Cell proliferation, gene and protein expression were measured to access the biological effects of the scaffolds on ADSCs, and the related molecular mechanism was investigated. Cross-linking by genipin increased the stability of the type II collagen scaffolds, but deformed the configuration of scaffolds and changed the intrinsic properties of type II collagen. scaffold cross-linked with 0.1% genipin improved the biostability on the basis of maintaining the configuration of scaffold. In addition, the 0.1% genipin-cross-linked scaffold promoted ADSCs proliferation and differentiation into NP-like cells, along with the increasing gene and protein expressions of Sonic Hedgehog (Shh). All these results suggested that 0.1% genipin was the optimal concentration to establish a bio-stable 3D type II collagen scaffold, which inducing ADSC proliferation and differentiation toward a NP-like phenotype through the activation of Shh signaling pathway. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1258-1268, 2018.

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Development of kartogenin-conjugated chitosan–hyaluronic acid hydrogel for nucleus pulposus regeneration

Cited by 64 publications

References 33 publications

Application of kartogenin for musculoskeletal regeneration

Application of kartogenin for musculoskeletal regeneration

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

Genipin‐cross‐linked type II collagen scaffold promotes the differentiation of adipose‐derived stem cells into nucleus pulposus‐like cells

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