Construction Strategy and Progress of Whole Intervertebral Disc Tissue Engineering

Yang, Qiang; Xu, Haiwei; Hurday, Sookesh; Xu, Bei

doi:10.1111/os.12218

Cited by 17 publications

(12 citation statements)

References 63 publications

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“…16–20 These scaffolds often contain a hydrogel core and circumferentially-constraining casing, which attempt to mimic the NP and AF, respectively and support cellular viability and extracellular matrix (ECM) production. 18 However, these implants often fail to match the geometry and size, biochemistry, micro-architecture and mechanical characteristics of native human IVD tissue. This suggests a need for a revised approach for creating whole-IVD scaffolds.…”

Section: Introductionmentioning

confidence: 99%

“…Alternatively, researchers have begun to develop whole-IVD scaffolds with the long-term goal of tissue engineering and replacing the entire IVD. [16][17][18][19][20] These scaffolds often contain a hydrogel core and circumferentially constraining casing, which attempt to mimic the NP and AF, respectively, and support cellular viability and extracellular matrix (ECM) production. 18 However, these implants often fail to match the geometry and size, biochemistry, microarchitecture and mechanical characteristics of native human IVD tissue.…”

Section: Introductionmentioning

confidence: 99%

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Decellularization and characterization of a whole intervertebral disk xenograft scaffold

Hensley

Rames

Casler

et al. 2018

J Biomedical Materials Res

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Intervertebral disk (IVD) degeneration is a multifactor process that results in the physical destruction of the nucleus pulposus (NP) and annulus fibrosus (AF). This compromises IVD function and causes significant disability and economic burden. Strategies to replace the entire composite structure of the IVD are limited and most approaches do not recapitulate the heterogenous biochemical composition, microarchitecture or mechanical properties of the native tissue. Our central hypothesis was that donor IVDs which resemble the size and biochemistry of human lumbar IVDs could be successfully decellularized while retaining the tissue's structure and function with the long-term goal of creating a composite scaffold for tissue engineering the human IVD. Accordingly, we optimized a procedure to decellularize bovine tail IVDs using a combination of detergents, ultrasonication, freeze-thaw cycles, and nucleases. The resultant decellularized whole IVD xenografts retained distinct AF and NP regions which contained no visible intact cell nuclei and minimal residual bovine deoxyribose nucleic acid (DNA; 65.98 ± 4.07 and 47.12 ± 13.22 ng/mg, respectively). Moreover, the NP region of decellularized IVDs contained 313.40 ± 50.67 µg/mg glycosaminoglycan. The presence of collagen type II was confirmed via immunohistochemistry. Additionally, histological analysis of the AF region of decellularized IVDs demonstrated retention of the native angle-ply collagen microarchitecture. Unconfined compression testing demonstrated no significant differences in swelling pressure and toe-region modulus between fresh and decellularized IVDs. However, linear region moduli, peak stress and equilibrium moduli were all significantly reduced. Together, this research demonstrates a successful initial step in developing a biomimetic acellular whole IVD xenograft scaffold for use in IVD tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2412-2423, 2018.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Decellularization and characterization of a whole intervertebral disk xenograft scaffold

Hensley

Rames

Casler

et al. 2018

J Biomedical Materials Res

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“…Existing therapies including spinal fusion and discectomy are mainly aimed to alleviate pain symptoms but not to biologically regenerate disc function. Currently, considerable efforts have been made toward biologically regenerating degenerative discs using tissue engineering approaches [5-9]. …”

Section: Introductionmentioning

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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“…Synthetic polyesters that are extensively used in AF tissue regeneration include poly(ε-caprolactone) [PCL], polylactide (PLA), polyglycolide (PGA), and copolymers produced from the respective monomers [26,59]. In addition, many other natural and synthetic materials are being investigated as scaffolds for AF, NP and IVD tissue engineering [60].…”

Section: Scaffolds and Appropriate Source Materialsmentioning

confidence: 99%

Intervertebral disc tissue engineering: A brief review

Stergar

Gradišnik

Velnar

et al. 2019

Bosn J of Basic Med Sci

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Intervertebral disc (IVD) degeneration (IDD) is associated with low back pain and significantly affects the patient’s quality of life. Degeneration of the IVD alters disk height and the mechanics of the spine, leading to chronic segmental spinal instability. The pathophysiology of IVD disease is still not well understood. Current therapies for IDD include conservative and invasive approaches, but none of those treatments are able to restore the disc structure and function. Recently, tissue engineering techniques emerged as a possible approach to treat IDD, by replacing a damaged IVD with scaffolds and appropriate cells. Advances in manufacturing techniques, material processing and development, surface functionalization, drug delivery systems and cell incorporation furthered the development of tissue engineering therapies. In this review, biomaterial scaffolds and cell-based therapies for IVD regeneration are briefly discussed.

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Construction Strategy and Progress of Whole Intervertebral Disc Tissue Engineering

Cited by 17 publications

References 63 publications

Decellularization and characterization of a whole intervertebral disk xenograft scaffold

Decellularization and characterization of a whole intervertebral disk xenograft scaffold

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

Intervertebral disc tissue engineering: A brief review

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