Geometric confinement is required for recovery and maintenance of chondrocyte phenotype in alginate.

Megan E Cooke,Christopher J Weston,Simon W Jones,Liam M Grover,Edward T Davis,Mark J Pearson,Richard J A Moakes

doi:10.1063/1.5006752

Megan E Cooke, Christopher J Weston + Show 5 more

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https://doi.org/10.1063/1.5006752

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Abstract

Human articular chondrocytes lose their native phenotype when expanded in traditional monolayer cultures. As a consequence, hydrogel encapsulation has been investigated as a means to maintain the natural phenotype. Alginate has been widely used for cartilage engineering as it has been shown to enable the recovery of a native collagen type II expressing chondrocyte phenotype. This study has evaluated whether the capacity of the materials to maintain/revert the phenotype is due to the composition of the material or the physical entrapment provided by the gel. To achieve this, an alginate “fluid gel” (a shear-thinning structured gel system) was produced of identical chemistry to a traditionally gelled alginate structure. Both were seeded with passaged primary human articular chondrocytes. Chondrocytes in quiescent alginate showed the recovery of the native phenotype and a spherical morphology. Chondrocytes in alginate fluid gel were unable to maintain the recovered phenotype despite having a spherical morphology and were shown to have a lower level of entrapment than those in quiescent alginate. These findings indicate that geometric entrapment is essential for the maintenance of a recovered chondrocyte phenotype in alginate.

Highlights

Osteoarthritis (OA) affects 25% of the over-50 population, which is expected to rise with the increasingly obese world population.[1,2] OA is characterized by the degeneration of articular cartilage, narrowing of the joint space, and pathological changes to subchondral bone; it is a painful and disabling condition.[3]
Alginate has been widely used for cartilage engineering as it has been shown to enable the recovery of a native collagen type II expressing chondrocyte phenotype
Chondrocytes in alginate fluid gel were unable to maintain the recovered phenotype despite having a spherical morphology and were shown to have a lower level of entrapment than those in quiescent alginate. These findings indicate that geometric entrapment is essential for the maintenance of a recovered chondrocyte phenotype in alginate

Summary

Introduction

Osteoarthritis (OA) affects 25% of the over-50 population, which is expected to rise with the increasingly obese world population.[1,2] OA is characterized by the degeneration of articular cartilage, narrowing of the joint space, and pathological changes to subchondral bone; it is a painful and disabling condition.[3] At present, there is no cure for OA, and many patients will eventually require joint replacement surgery. The native cartilage matrix is rich in collagen type II, proteoglycans, and chondrocytes, the cartilage-matrix producing cells.[4]. Articular cartilage is avascular and has a limited capacity for self-regeneration. It is widely believed that in end-stage OA, the cartilage loss is irreversible. As an avascular tissue, the delivery of pharmacological entities to the cells of the cartilage, the chondrocytes, is highly challenging

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