Integration of layered chondrocyte-seeded alginate hydrogel scaffolds

Lee, Christopher S.D.; Gleghorn, Jason P.; Choi, Nakwon; Cabodi, Mario; Stroock, Abraham D.; Bonassar, Lawrence J.

doi:10.1016/j.biomaterials.2007.02.035

Cited by 93 publications

(84 citation statements)

References 28 publications

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“…As a typical soft matter, polymer gels have attracted increasing attention with respect to fundamental research and their applications in the fields of biosensors, [1,2] drug delivery, [3,4] bioseparations, [5,6] tissue engineering [7,8] and smart devices. [9,10] New applications also call for many new requirements concerning their mechanical properties, transparency, environmental sensitivity and biocompatibility.…”

Section: Introductionmentioning

confidence: 99%

High‐Strength Cellulose/Poly(ethylene glycol) Gels

Liang

Tian

et al. 2008

ChemSusChem

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Cellulose gel membranes have been prepared by a pre-gelation method employing cellulose solutions in aqueous NaOH-thiourea obtained at low temperature. The cellulose gels were then swollen by low-molecular-weight polyethylene glycol (PEG; MW<1000 g mol(-1)), and the morphology, structure and mechanical properties of the cellulose/PEG gels were studied by various techniques. The gels exhibit high mechanical performance, and the tensile strength of the gel membranes increases sharply with an increase in the molecular weight of PEG from 200 to 800 g mol(-1). Moreover, their elongation at break remains stable at 100 %. PEG800 efficiently improves the optical transmittance of the gel membranes at ambient temperature, which is about five times greater than that of a normal cellulose hydrogel membrane. A strong hydrogen-bonding interaction occurs between PEG and cellulose leading to a homogeneous structure, high mechanical strength and good transparency of the gel membranes.

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Section: Introductionmentioning

confidence: 99%

High‐Strength Cellulose/Poly(ethylene glycol) Gels

Liang

Tian

et al. 2008

ChemSusChem

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“…Cartilage tissue equivalents derived from hydrogels containing chondrocytes could provide a solution for repairing or replacing damaged cartilage 9–11 . Various hydrogels, such as poly-ethylene glycol 12 , agarose 13 , alginate 9 , hyaluronic acid 14 , and collagen 15 have been used for 3D culture of chondrocytes, and some aspects of cartilage tissue have been replicated in these hydrogels 15 .…”

mentioning

confidence: 99%

“…Various hydrogels, such as poly-ethylene glycol 12 , agarose 13 , alginate 9 , hyaluronic acid 14 , and collagen 15 have been used for 3D culture of chondrocytes, and some aspects of cartilage tissue have been replicated in these hydrogels 15 . However, proliferation of chondrocytes can be limited 16 and cartilage matrix deposition often occurs only immediately adjacent to the cells leading to islands of cartilage matrix within a sea of hydrogel 15,17 .…”

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confidence: 99%

Mechanical confinement regulates cartilage matrix formation by chondrocytes

et al. 2017

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Cartilage tissue equivalents formed from hydrogels containing chondrocytes could provide a solution for replacing damaged cartilage. Previous approaches have often utilized elastic hydrogels. However, elastic stresses may restrict cartilage matrix formation and alter the chondrocyte phenotype. Here we investigated the use of viscoelastic hydrogels, in which stresses are relaxed over time and which exhibit creep, for 3D culture of chondrocytes. We found that faster relaxation promoted a striking increase in the volume of interconnected cartilage matrix formed by chondrocytes. In slower relaxing gels, restriction of cell volume expansion by elastic stresses led to increased secretion of IL-1β, which in turn drove strong up-regulation of genes associated with cartilage degradation and cell death. As no cell adhesion ligands are presented by the hydrogels, these results reveal cell sensing of cell volume confinement as an adhesion-independent mechanism of mechanotransduction in 3D culture, and highlight stress relaxation as a key design parameter for cartilage tissue engineering.

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“…1,17,19,[21][22][23][24] Similar to compressive load, reports of reduced ECM accumulation have been observed as a consequence of perfusion, which appears to move newly synthesized proteins into the medium. 25,26 Few studies examined the combined effects of loading and medium perfusion. Seidel et al 27 used a perfused chamber combined with mechanical loading, which led to increased GAG deposition.…”

Section: Introductionmentioning

confidence: 99%

Effects of Perfusion and Dynamic Loading on Human Neocartilage Formation in Alginate Hydrogels

Grogan

Sovani

Pauli

et al. 2012

Tissue Engineering Part A

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Dynamic loading and perfusion culture environments alone are known to enhance cartilage extracellular matrix (ECM) production in dedifferentiated articular chondrocytes. In this study, we explored whether a combination of these factors would enhance these processes over a free-swelling (FS) condition using adult human articular chondrocytes embedded in 2% alginate. The alginate constructs were placed into a bioreactor for perfusion (P) only (100 mL/per minute) or perfusion and dynamic compressive loading (PL) culture (20% for 1 h, at 0.5 Hz), each day. Control FS alginate gels were maintained in six-well static culture. Gene expression analysis was conducted on days 7 and 14, while cell viability, immunostaining, and mechanical property testing were performed on day 14 only. Total glycosaminoglycan (GAG) content and GAG synthesis were assessed after 14 days. Col2a1 mRNA expression levels were significantly higher (at least threefold; p < 0.05) in both bioreactor conditions compared with FS by days 7 and 14. For all gene studies, no significant differences were seen between P and PL treatments. Aggrecan mRNA levels were not significantly altered in any condition although both GAG/ DNA and 35 S GAG incorporation studies indicated higher GAG retention and synthesis in the FS treatment. Collagen type II protein deposition was low in all samples, link protein distribution was more diffuse in FS condition, and aggrecan deposition was located in the outer regions of the alginate constructs in both bioreactor conditions, yet more uniformly in the FS condition. Catabolic gene expression (matrix metalloproteinase 3 [MMP3] and inducible nitric oxide synthase [iNOS]) was higher in bioreactor conditions compared with FS, although iNOS expression levels decreased to approximately fourfold less than the FS condition by day 14. Our data indicate that conditions created in the bioreactor enhanced both anabolic and catabolic responses, similar to other loading studies. Perfusion was sufficient alone to promote this dual response. PL increased the deposition of aggrecan surrounding cells compared with the other conditions; however, overall low GAG retention in the bioreactor system was likely due to both perfusion and catabolic conditions created. Optimal conditions, which permit appropriate anabolic and catabolic processes for accumulation of ECM and tissue remodeling for neocartilage development, specifically for humans, are needed.

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Integration of layered chondrocyte-seeded alginate hydrogel scaffolds

Cited by 93 publications

References 28 publications

High‐Strength Cellulose/Poly(ethylene glycol) Gels

High‐Strength Cellulose/Poly(ethylene glycol) Gels

Mechanical confinement regulates cartilage matrix formation by chondrocytes

Effects of Perfusion and Dynamic Loading on Human Neocartilage Formation in Alginate Hydrogels

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