Chondrocyte Culture in Three Dimensional Alginate Sulfate Hydrogels Promotes Proliferation While Maintaining Expression of Chondrogenic Markers

Mhanna, Rami; Kashyap, Aditya; Palazzolo, Gemma; Vallmajó-Martín, Queralt; Becher, Jana; Möller, Stephanie; Schnabelrauch, Matthias; Zenobi‐Wong, Marcy

doi:10.1089/ten.tea.2013.0544

Cited by 100 publications

(102 citation statements)

References 49 publications

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“…The formation of filopodia has previously been found to be mediated by integrin beta 1 interaction with sulphated alginate, providing cell attachment points and potentially increasing proliferation through stimulated Cyclin D gene expression (Mhanna et al, 2014). There was, in the present study, no observable relation between cell viability and morphology and the mechanical properties/sulphate content of the gels.…”

Section: ø Arlov Et Al Biomimetic Sulphated Alginate Hydrogelscontrasting

confidence: 56%

“…Proteolytic degradation of the matrix can also release immobilised cytokines such as interleukin (IL)-1β and IL-6 and tumour necrosis factor (TNF) which in turn further induce cytokine expression and secretion of matrix-degrading enzymes from chondrocytes, thus propagating tissue breakdown (David et al, 2007;Martel-Pelletier, 1999). These effects are largely mediated by nuclear transcription factors such as nuclear factor-kappaB (NF-κB), which has been shown to induce expression of inflammatory cytokines, matrix metalloproteinases (MMPs), cyclooxygenase-2 (COX-2), as well as adhesion molecules (ICAM-1, VCAM-1 and E-selectin) implicating NF-κB in the recruitment of leukocytes (Ke et al, 2007;Miagkov et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

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Biomimetic sulphated alginate hydrogels suppress IL-1β-induced inflammatory responses in human chondrocytes

Arlov¹,

Öztürk²,

Steinwachs³

et al. 2017

eCM

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Loss of articular cartilage from ageing, injury or degenerative disease is commonly associated with inflammation, causing pain and accelerating degradation of the cartilage matrix. Sulphated glycosaminoglycans (GAGs) are involved in the regulation of immune responses in vivo, and analogous polysaccharides are currently being evaluated for tissue engineering matrices to form a biomimetic environment promoting tissue growth while suppressing inflammatory and catabolic activities. Here, we characterise physical properties of sulphated alginate (S-Alg) gels for use in cartilage engineering scaffolds, and study their anti-inflammatory effects on encapsulated chondrocytes stimulated with IL-1β. Sulphation resulted in decreased storage modulus and increased swelling of alginate gels, whereas mixing highly sulphated alginate with unmodified alginate resulted in improved mechanical properties compared to gels from pure S-Alg. S-Alg gels showed extensive anti-inflammatory and anti-catabolic effects on encapsulated chondrocytes induced by IL-1β. Cytokine-stimulated gene expression of pro-inflammatory markers IL-6, IL-8, COX-2 and aggrecanase ADAMTS-5 were significantly lower in the sulphated gels compared to unmodified alginate gels. Moreover, sulphation of the microenvironment suppressed the protein expression of COX-2 and NF-κB as well as the activation of NF-κB and p38-MAPK. The sulphated alginate matrices were found to interact with IL-1β, and proposed to inhibit inflammatory induction by sequestering cytokines from their receptors. This study shows promising potential for sulphated alginates in biomimetic tissue engineering scaffolds, by reducing cytokine-mediated inflammation and providing a protective microenvironment for encapsulated cells.

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Section: ø Arlov Et Al Biomimetic Sulphated Alginate Hydrogelscontrasting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Biomimetic sulphated alginate hydrogels suppress IL-1β-induced inflammatory responses in human chondrocytes

Arlov¹,

Öztürk²,

Steinwachs³

et al. 2017

eCM

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“…(30,31) Indeed, structures fabricated from highly hydrophilic polymers do not lend themselves to protein adsorption and are therefore poor substrates for cellular adhesion. (11,30) This characteristic has been largely observed in vitro for osteoblasts, (32,33) skeletal myoblasts, (34) chondrocytes, (35,36) hepatocytes (37) and nucleus pulposus cells, (38,39) where cells exhibited weak adhesion and proliferation after encapsulation in unmodified alginate.…”

Section: Discussionmentioning

confidence: 93%

Enhancing cell migration in shape-memory alginate–collagen composite scaffolds: In vitro and ex vivo assessment for intervertebral disc repair

et al. 2014

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Lower lumbar disc disorders pose a significant problem in an ageing society with substantial socioeconomic consequences. Both inner tissue (nucleus pulposus, NP) and outer tissue (annulus fibrosus, AF) of the intervertebral disc (IVD) are affected by such debilitating disorders and can lead to disc herniation and lower back pain. In this study, we developed an alginate-collagen composite porous scaffold with shape-memory properties to fill defects occurring in AF tissue of degenerated IVDs, which has the potential to be administered using minimal invasive surgery. In the first part of this work we assessed how collagen incorporation on pre-formed alginate scaffolds influences the physical properties of the final composite scaffold. We also evaluated the ability of AF cells to attach, migrate and proliferate on the composite alginate-collagen scaffolds compared to control scaffolds (alginate only). In vitro experiments, performed in IVD-like microenvironmental conditions (low glucose and low oxygen concentrations), revealed that for alginate only scaffolds, AF cells agglomerated in clusters with limited infiltration and migration capacity. In comparison, for alginatecollagen scaffolds, AF cells readily attached and colonized constructs, while preserving their typical fibroblastic-like cell morphology with spreading behavior and intense cytoskeleton expression. In a second part of this study, we investigated the effects of alginate-collagen scaffold when seeded with bone marrow derived mesenchymal stem cells (MSCs). In vitro, we observed that alginate-collagen porous scaffolds supported cell proliferation and extracellular matrix (ECM) deposition (collagen type I); which secretion was amplified by the local release of TGF-ß3. In addition, when cultured in ex vivo organ defect model, alginatecollagen scaffolds maintained viability of transplanted MSCs for up to 5 weeks. Taken together, these findings illustrate the advantages of incorporating collagen as a means to enhance cell migration and proliferation in porous scaffolds which could be used to augment tissue repair strategies.

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“…All the procedures described below were performed in sterile conditions. Cells were resuspended in the alginate solution (0.1-0.4% w/v) at a density of 10 7 cells/mL and the neuron laden hydrogels were produced using disc casters (QGel SA), as described in Mhanna et al 26 with some modifications. Briefly, 30 mL of the neuron hydrogel suspension was placed into the caster with 1.5 mm spacing which, in turn, was dipped into DMEM supplemented with 10% FBS, 2 mM Glutamax, 100 U/mL penicillin, 100 mg/mL streptomycin, and 10 mM CaCl 2 to allow the gelation for 30 min at RT.…”

Section: Alginate Hydrogel Preparationmentioning

confidence: 99%

Ultrasoft Alginate Hydrogels Support Long-Term Three-Dimensional Functional Neuronal Networks

Palazzolo

Broguière

Cenciarelli

et al. 2015

Tissue Engineering Part A

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Neuron development and function are exquisitely sensitive to the mechanical properties of their surroundings. Three-dimensional (3D) cultures are therefore being explored as they better mimic the features of the native extracellular matrix. Limitations of existing 3D culture models include poorly defined composition, rapid degradation, and suboptimal biocompatibility. Here we show that ionically cross-linked ultrasoft hydrogels made from unmodified alginate can potently promote neuritogenesis. Alginate hydrogels were characterized mechanically and a remarkable range of stiffness (10-4000 Pa) could be produced by varying the macromer content (0.1-0.4% w/v) and CaCl2 concentration. Dissociated rat embryonic cortical neurons encapsulated within the softest of the hydrogels (0.1% w/v, 10 mM CaCl2) showed excellent viability, extensive formation of axons and dendrites, and long-term activity as determined by calcium imaging. In conclusion, alginate is an off-the-shelf, easy to handle, and inexpensive material, which can be used to make ultrasoft hydrogels for the formation of stable and functional 3D neuronal networks. This 3D culture system could have important applications in neuropharmacology, toxicology, and regenerative medicine.

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Chondrocyte Culture in Three Dimensional Alginate Sulfate Hydrogels Promotes Proliferation While Maintaining Expression of Chondrogenic Markers

Cited by 100 publications

References 49 publications

Biomimetic sulphated alginate hydrogels suppress IL-1β-induced inflammatory responses in human chondrocytes

Biomimetic sulphated alginate hydrogels suppress IL-1β-induced inflammatory responses in human chondrocytes

Enhancing cell migration in shape-memory alginate–collagen composite scaffolds: In vitro and ex vivo assessment for intervertebral disc repair

Ultrasoft Alginate Hydrogels Support Long-Term Three-Dimensional Functional Neuronal Networks

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