Bioengineered three-dimensional diseased intervertebral disc model revealed inflammatory crosstalk

Srivastava, Akshay; Isa, Isma Liza Mohd; Rooney, Peadar; Pandit, Abhay

doi:10.1016/j.biomaterials.2017.01.045

Cited by 32 publications

(31 citation statements)

References 71 publications

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“…We have a long history of using PEG‐NH 2 cross‐linked HA for a wide range of biomedical applications; delivery of plasmid DNA, [ 24,25 ] scaffolding, [ 26,27 ] anti‐inflammatory, [ 28,29 ] and for inhibiting angiogenesis and retinal vascular permeability. [ 30 ]…”

Section: Resultsmentioning

confidence: 99%

“…The cHA reported in this study is a non‐sized, high molecular weight HA, cross‐linked via a 4‐arm polyethylene glycol amine (PEG‐NH 2 ) linker using 4‐(4,6‐dimethoxy‐1,3,5‐triazin‐2‐yl)‐4‐methyl‐morpholinium chloride (DMTMM) chemistry and adapted for GMP production. The proposed methodology for cross‐linking HA using PEG‐NH 2 is an iterative outcome of our previously reported procedures [ 24–30 ] combining the current strategies for amide coupling reported in the literature. [ 31,32 ] Herein, we demonstrate DMTMM as an efficient and optimal reagent for cross‐linking high molecular weight HA with PEG‐NH 2 when compared to 1‐ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide/ N‐ hydroxysuccinimide (EDC/NHS) (Scheme 2).…”

Section: Introductionmentioning

confidence: 99%

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Crossing the hurdles of translation—a robust methodology for synthesis, characterization and GMP production of cross‐linked high molecular weight hyaluronic acid particles (cHA)

et al. 2020

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Hyaluronic acid (HA) is one of the most widely used extracellular matrix substrate in tissue engineering, drug delivery, and other clinical applications, due to its unique physiochemical properties and ubiquitous biological presence. In the past decade, there has been a surge in research paradigms involving HA products to evaluate their commercial feasibility. Numerous papers and reviews have reported procedures for chemical modifications and cross‐linking of HA, but the intricacies of their scale‐up in the production processes are often not discussed. Protected by confidentiality agreements with industry partners, information on these procedures is exclusive and not accessible within an academic setting. Establishing translatable synthetic protocols of HA would address this significant gap in the field and facilitate their use in other applications. The current method details a reproducible and robust method for producing particles that are composed of high molecular weight hyaluronic acid (cHA) and cross‐linked via a 4‐arm polyethylene glycol amine linker using 4‐(4,6‐dimethoxy‐1,3,5‐triazin‐2‐yl)‐4‐methyl‐morpholinium chloride chemistry. A critical analysis of previously reported procedures for their advantages and limitations (reaction parameters, molar equivalents, and reagents used for cross‐linking), forms the basis for this procedure and its subsequent adaptation to good manufacturing practices requirements. As a component of a Class III medical device, the reported cHA is in the form of non‐sized particles.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Crossing the hurdles of translation—a robust methodology for synthesis, characterization and GMP production of cross‐linked high molecular weight hyaluronic acid particles (cHA)

et al. 2020

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“…NP and AF cells were seeded in the respective regions of the constructs at similar concentration to that found in the IVD. [ 108 ] As the previous authors, they have induced a proinflammatory environment by IL‐1β stimulation and investigated the paracrine cytokine release and matrix degradation. Besides the development of this competent model, they were able to identify the role of the suppressor of cytokine proteins (SOCS) family in combating detrimental effects of proinflammatory cytokines in degenerated human NP tissue and have observed an increase expression of neurotrophic factors as NGF and BDNF in both AF and NP cells.…”

Section: Advanced Models Of Inflammation For Ivd Degenerationmentioning

confidence: 99%

“…Both models offer the possibility of being refined with the native features, such as low oxygen and glucose or dynamic loading, thus representing important cost‐effective platforms prior to translation to in vivo models, and being adequate to evaluate the feasibility of new therapies for IVD and associated pain treatment in vitro. [ 108 ] Alginate microspheres are largely applied for 3D cell culture and have been also used as 3D models to evaluate the effects of proinflammatory cytokines on IVD cells, or to evaluate the potential therapies for painful IVDs treatment. [ 109 ] Krupkova et al evaluated the effect of the biologically active polyphenol epigallocatechin 3‐gallate (EGCG) in alginate‐3D cultures of cells from patients with disc degenerative disease, under a proinflammatory stimulus (IL‐1β).…”

Section: Advanced Models Of Inflammation For Ivd Degenerationmentioning

confidence: 99%

Articular Repair/Regeneration in Healthy and Inflammatory Conditions: From Advanced In Vitro to In Vivo Models

Teixeira

Pereira

Almeida

et al. 2020

Adv Funct Materials

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The burden of chronic inflammatory diseases of joints and the spine is increasing with population ageing and unhealthy lifestyles. Articular cartilage and intervertebral discs (IVDs) are avascular and aneural tissues with abundant extracellular matrix, low cell density, and reduced regenerative capacity after damage or degeneration. The most advanced in vitro and ex vivo cell-/tissue-/biomaterial-based models and technologies to improve physiological mimicry are discussed, focusing on the impact of inflammation on articular repair/regeneration. In addition, in vivo models, developed to study cartilage and IVD repair/regeneration are addressed. While animal models continue to provide crucial mechanistic and preclinical data, more advanced and robust in vitro/ex vivo cartilage and IVD models, with appropriate extracellular matrix cues and allowing for cellular crosstalk, have seen an exponential growth in the last decade. Due to the complexity of articular microenvironments, adequate in vitro/ex vivo/in vivo models are essential to study the molecular mechanisms underlying articular diseases and develop new therapies for repair/regeneration.

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“…Recently, the preconditioning of NP cells and autologous NP cell‐mediated therapies have aimed to rejuvenate and replenish the depleted NP tissue following injury or degeneration . However, many of the molecular pathways and signals that allow for successful redifferentiation and therapeutic targeting have yet to be fully elucidated . Wnt (Wingless protein family) signals are one of the well‐conserved pathways which have been extensively studied and implicated in tissue homeostasis, NP apoptosis, and, more specifically, in cell migration and differentiation, with particularly notable roles in chondrogenesis .…”

mentioning

confidence: 99%

Impact of Wnt signals on human intervertebral disc cell regeneration

Pizzute

Zhang

et al. 2018

Journal Orthopaedic Research

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Although preconditioning strategies are growing areas of interest for therapies targeting intervertebral discs (IVDs), it is unknown whether the Wnt signals previously implicated in chondrogenesis, Wnt3A, Wnt5A, and Wnt11, play key roles in the promotion of human nucleus pulposus (NP) cell redifferentiation. In this study, NP cells isolated from herniated disc patients were transduced with lentiviral vectors to overexpress the WNT3A, WNT5A, or WNT11 genes, or CRISPR associated protein 9 (Cas9)/single-guide RNA (sgRNA) vectors to knock out these genes. Following expansion, transduced NP cells were induced for redifferentiation toward the NP phenotype. The overexpression of specific WNT factors led to increases in both glycosaminoglycan (GAG) deposition and expression of redifferentiation genes. These effects were attenuated by knockout of the same WNT genes. These results indicate that specific WNT signals can regulate the expression of redifferentiation genes, unequally impact GAG deposition, and contribute to the redifferentiation of human NP cells. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

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Bioengineered three-dimensional diseased intervertebral disc model revealed inflammatory crosstalk

Cited by 32 publications

References 71 publications

Crossing the hurdles of translation—a robust methodology for synthesis, characterization and GMP production of cross‐linked high molecular weight hyaluronic acid particles (cHA)

Crossing the hurdles of translation—a robust methodology for synthesis, characterization and GMP production of cross‐linked high molecular weight hyaluronic acid particles (cHA)

Articular Repair/Regeneration in Healthy and Inflammatory Conditions: From Advanced In Vitro to In Vivo Models

Impact of Wnt signals on human intervertebral disc cell regeneration

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