The Effect of Biomolecular Gradients on Mesenchymal Stem Cell Chondrogenesis under Shear Stress

Harihara Baskaran,Alexander Rivera

doi:10.3390/mi6030330

Harihara Baskaran, Alexander Rivera

Open Access

https://doi.org/10.3390/mi6030330

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Journal: Micromachines	Publication Date: Mar 1, 2015
Citations: 8	License type: CC BY 4.0

Affiliation: Case Western Reserve University

Abstract

Tissue engineering is viewed as a promising option for long-term repair of cartilage lesions, but current engineered cartilage constructs fail to match the mechanical properties of native tissue. The extracellular matrix of adult human articular cartilage contains highly organized collagen fibrils that enhance the mechanical properties of the tissue. Unlike articular cartilage, mesenchymal stem cell (MSC) based tissue engineered cartilage constructs lack this oriented microstructure and therefore display much lower mechanical strength. The goal of this study was to investigate the effect of biomolecular gradients and shear stress on MSCs undergoing chondrogenesis within a microfluidic device. Via poly(dimethyl siloxane) soft-lithography, microfluidic devices containing a gradient generator were created. Human MSCs were seeded within these chambers and exposed to flow-based transforming growth factor β1 (TGF-β1) gradients. When the MSCs were both confluent and exposed to shear stress, the cells aligned along the flow direction. Exposure to TGF-β1 gradients led to chondrogenesis of MSCs, indicated by positive type II collagen staining. These results, together with a previous study that showed that aligned MSCs produce aligned collagen, suggest that oriented cartilage tissue structures with superior mechanical properties can be obtained by aligning MSCs along the flow direction and exposing MSCs to chondrogenic gradients.

Highlights

Osteoarthritis, characterized by the degeneration of cartilage that lines the articulating surfaces of bones, is a debilitating condition that affects over 48 million individuals in the United States alone [1,2].Articular cartilage is an avascular tissue with a poor intrinsic healing capability; clinical methods are necessary to relieve the symptoms and repair the damaged tissue
This study investigated the use of a gradient generating microfluidic device to study the effects of fluid flow-induced shear stress on Mesenchymal stem cell (MSC) alignment and biomolecular gradients on MSC chondrogenesis
Since the gradient-generating device used in this study develops gradients via fluid flow, it can be used to study the effects of shear stress on MSC alignment, which may be utilized to control extracellular matrix (ECM) structure

Summary

Introduction

Osteoarthritis, characterized by the degeneration of cartilage that lines the articulating surfaces of bones, is a debilitating condition that affects over 48 million individuals in the United States alone [1,2].Articular cartilage is an avascular tissue with a poor intrinsic healing capability; clinical methods are necessary to relieve the symptoms and repair the damaged tissue. The MSCs are combined with scaffolds and chondrogenic signaling molecules to produce cartilage constructs [5,6,7,8,9,10,11,12] Despite these advances, tissue-engineered cartilage constructs display inferior mechanical strength compared to native cartilage. Microfluidic gradient generators have been useful to study several biological processes such as pro- and eukaryotic cell chemotaxis [16,17] and neural stem cell proliferation and differentiation [18]. These devices can be fabricated by photo- and soft-lithography methods, made of poly(dimethyl siloxane) (PDMS), and are amenable to cell culture. In a previous study, aligned MSCs undergoing chondrogenesis synthesized aligned type II collagen and resulted in tissue constructs with enhanced mechanical properties [19]

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