Abstract

A novel multi-axial bioreactor was designed and developed to deliver combinations of the following dynamic mechanical stimulation conditions: hydrostatic pressure, pulsatile perfusion flow and uniaxial compression in order to mimic in vivo conditions. This mechanical arrangement simultaneously allows triaxial stimulation and characterization of mechanical properties of samples, in particular simulating the conditions experienced by the nucleus pulposus in vivo. A series of initial experiments were performed on this prototype system using consistent, commercially-available, three dimensional scaffolds in combination with human dermal fibroblasts. Our results show that while such bioreactors hold much promise in tissue engineering of desired organs, achieving the right combination of mechanical stimuli and other conditions required in order to enhance the final properties of the cell-scaffold systems is challenging.

Highlights

  • The presence of mechanical stimuli has been shown to instigate cell differentiation [1,2,3,4,5,6]

  • This study aimed at the development of a bioreactor that could mimic the in vivo conditions experienced by the human vertebral disc: compression, hydrostatic pressure and pulsatile fluid flow forces

  • We have demonstrated the instruction and operation of a three-dimensional cell culture system

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Summary

Introduction

The presence of mechanical stimuli has been shown to instigate cell differentiation [1,2,3,4,5,6]. Inappropriately applied stimulus may cause cells to differentiate towards an undesirable lineage and even cell apoptosis resulting in tissue degeneration [8]. De and Safran [9] have previously shown that, in a cell-scaffold construct, the resulting stiffness of the matrix is a function of cellular response to the external mechanical stimulus at a particular frequency. While back pain due to intervertebral disc degeneration is a common problem, little is understood about the cells that make up the nucleus pulposus, the gel-like component of the disc. The nucleus pulposus becomes less gelatinous, leading to cracks and fissures [10]

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