Sulfated Hydrogels in Intervertebral Disc and Cartilage Research

Lazarus, Emily; Bermudez-Lekerika, Paola; Farchione, Daniel; Schofield, Taylor; Howard, S; Mambetkadyrov, Iskender; Lamoca, Mikkael; Rivero, Iris V.; Gantenbein, Benjamin; Lewis, Christopher L.; Wuertz‐Kozak, Karin

doi:10.3390/cells10123568

Cited by 5 publications

(4 citation statements)

References 51 publications

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“…Alginate has been extensively employed in IVD research due to its structural similarity to native ECM, low toxicity [29], high biocompatibility [30] and ability to be modified [31]. Nevertheless, although alginate is considered a gold-standard hydrogel in IVD and cartilage fields [32], it lacks a crucial feature which is present in IVD and cartilage ECM: the sulfonic groups of proteoglycans responsible for negatively charged microenvironments [33,34]. Native IVD ECM is mainly composed of proteoglycans, which consist of a core protein modified by linear sulfated glycosaminoglycans (GAGs), responsible for osmotically water attraction conferring mechanical stability and local biological environment modulation.…”

Section: Introductionmentioning

confidence: 99%

Sulfated Hydrogels as Primary Intervertebral Disc Cell Culture Systems

Bermudez-Lekerika,

Crump,

Wuertz-Kozak

et al. 2024

Gels

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The negatively charged extracellular matrix plays a vital role in intervertebral disc tissues, providing specific cues for cell maintenance and tissue hydration. Unfortunately, suitable biomimetics for intervertebral disc regeneration are lacking. Here, sulfated alginate was investigated as a 3D culture material due to its similarity to the charged matrix of the intervertebral disc. Precursor solutions of standard alginate, or alginate with 0.1% or 0.2% degrees of sulfation, were mixed with primary human nucleus pulposus cells, cast, and cultured for 14 days. A 0.2% degree of sulfation resulted in significantly decreased cell density and viability after 7 days of culture. Furthermore, a sulfation-dependent decrease in DNA content and metabolic activity was evident after 14 days. Interestingly, no significant differences in cell density and viability were observed between surface and core regions for sulfated alginate, unlike in standard alginate, where the cell number was significantly higher in the core than in the surface region. Due to low cell numbers, phenotypic evaluation was not achieved in sulfated alginate biomaterial. Overall, standard alginate supported human NP cell growth and viability superior to sulfated alginate; however, future research on phenotypic properties is required to decipher the biological properties of sulfated alginate in intervertebral disc cells.

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Section: Introductionmentioning

confidence: 99%

Sulfated Hydrogels as Primary Intervertebral Disc Cell Culture Systems

Bermudez-Lekerika,

Crump,

Wuertz-Kozak

et al. 2024

Gels

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“…However, utilizing these targets requires more in-depth and extensive trials conducted by experts in the field. Furthermore, an ongoing challenge is achieving effective long-term release of therapeutic cells or factors in the IVD( Lazarus et al., 2021 ). With the advancement of bioengineering scholars have investigated a biomaterial akin to medullary tissue - hydrogel.…”

Section: Discussionmentioning

confidence: 99%

From drugs to biomaterials: a review of emerging therapeutic strategies for intervertebral disc inflammation

Yang,

Jing,

Wang

et al. 2024

Front. Cell. Infect. Microbiol.

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Chronic low back pain (LBP) is an increasingly prevalent issue, especially among aging populations. A major underlying cause of LBP is intervertebral disc degeneration (IDD), often triggered by intervertebral disc (IVD) inflammation. Inflammation of the IVD is divided into Septic and Aseptic inflammation. Conservative therapy and surgical treatment often fail to address the root cause of IDD. Recent advances in the treatment of IVD infection and inflammation range from antibiotics and small-molecule drugs to cellular therapies, biological agents, and innovative biomaterials. This review sheds light on the complex mechanisms of IVD inflammation and physiological and biochemical processes of IDD. Furthermore, it provides an overview of recent research developments in this area, intending to identify novel therapeutic targets and guide future clinical strategies for effectively treating IVD-related conditions.

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“…Moreover, modified alginates have shown novel properties and applications in biomedical research ( Rosiak et al, 2021 ). For example, the sulfation of alginate hydrogel has been reported to preserve the phenotype of chondrocytes ( Öztürk et al, 2016 ; Lazarus et al, 2021 ). Thus, alginate-based hydrogel systems are considered as promising biological constructs for NP cell culture ( Thorpe et al, 2018 ).…”

Section: Research Methods For Exploring the Inflammatory Or Catabolic...mentioning

confidence: 99%

Immuno-Modulatory Effects of Intervertebral Disc Cells

Bermudez-Lekerika

Crump

Tseranidou

et al. 2022

Front. Cell Dev. Biol.

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Low back pain is a highly prevalent, chronic, and costly medical condition predominantly triggered by intervertebral disc degeneration (IDD). IDD is often caused by structural and biochemical changes in intervertebral discs (IVD) that prompt a pathologic shift from an anabolic to catabolic state, affecting extracellular matrix (ECM) production, enzyme generation, cytokine and chemokine production, neurotrophic and angiogenic factor production. The IVD is an immune-privileged organ. However, during degeneration immune cells and inflammatory factors can infiltrate through defects in the cartilage endplate and annulus fibrosus fissures, further accelerating the catabolic environment. Remarkably, though, catabolic ECM disruption also occurs in the absence of immune cell infiltration, largely due to native disc cell production of catabolic enzymes and cytokines. An unbalanced metabolism could be induced by many different factors, including a harsh microenvironment, biomechanical cues, genetics, and infection. The complex, multifactorial nature of IDD brings the challenge of identifying key factors which initiate the degenerative cascade, eventually leading to back pain. These factors are often investigated through methods including animal models, 3D cell culture, bioreactors, and computational models. However, the crosstalk between the IVD, immune system, and shifted metabolism is frequently misconstrued, often with the assumption that the presence of cytokines and chemokines is synonymous to inflammation or an immune response, which is not true for the intact disc. Therefore, this review will tackle immunomodulatory and IVD cell roles in IDD, clarifying the differences between cellular involvements and implications for therapeutic development and assessing models used to explore inflammatory or catabolic IVD environments.

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Sulfated Hydrogels in Intervertebral Disc and Cartilage Research

Cited by 5 publications

References 51 publications

Sulfated Hydrogels as Primary Intervertebral Disc Cell Culture Systems

Sulfated Hydrogels as Primary Intervertebral Disc Cell Culture Systems

From drugs to biomaterials: a review of emerging therapeutic strategies for intervertebral disc inflammation

Immuno-Modulatory Effects of Intervertebral Disc Cells

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