Abstract

Tissue engineering is a promising technique for cartilage repair. Toward this goal, a porous collagen–glycosaminoglycan (CG) scaffold was loaded with different concentrations of insulin-like growth factor-1 (IGF-1) and evaluated as a growth factor delivery device. The biological response was assessed by monitoring the amount of type II collagen and proteoglycan synthesised by the chondrocytes seeded within the scaffolds. IGF-1 release was dependent on the IGF-1 loading concentration used to adsorb IGF-1 onto the CG scaffolds and the amount of IGF-1 released into the media was highest at day 4. This initial IGF-1 release could be modelled using linear regression analysis. Osteoarthritic (OA) chondrocytes seeded within scaffolds containing adsorbed IGF-1 deposited decorin and type II collagen in a dose dependent manner and the highest type II collagen deposition was achieved via loading the scaffold with 50 μg/ml IGF-1. Cells seeded within the IGF-1 loaded scaffolds also deposited more extracellular matrix than the no growth factor control group thus the IGF-1 released from the scaffold remained bioactive and exerted an anabolic effect on OA chondrocytes. The effectiveness of adsorbing IGF-1 onto the scaffold may be due to protection of the molecule from proteolytic digestion allowing a more sustained release of IGF-1 over time compared to adding multiple doses of exogenous growth factor. Incorporating IGF-1 into the CG scaffold provided an initial therapeutic burst release of IGF-1 which is beneficial in initiating ECM deposition and repair in this in vitro model and shows potential for developing this delivery device in vivo.

Highlights

  • The unique biomechanical properties of articular cartilage are attributed to the complex zonal arrangement of its constituent macromolecules, collagen and proteoglycan

  • Cells seeded within the insulin-like growth factor-1 (IGF-1) loaded scaffolds deposited more extracellular matrix than the no growth factor control group the IGF-1 released from the scaffold remained bioactive and exerted an anabolic effect on OA chondrocytes

  • Incorporating IGF-1 into the CG scaffold provided an initial therapeutic burst release of IGF-1 which is beneficial in initiating extracellular matrix (ECM) deposition and repair in this in vitro model and shows potential for developing this delivery device in vivo

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Summary

Introduction

The unique biomechanical properties of articular cartilage are attributed to the complex zonal arrangement of its constituent macromolecules, collagen and proteoglycan. Surgical treatment of cartilage defects mainly yields suboptimal fibrous repair tissue. Inadequate cartilage repair tissue fails to withstand the biomechanical forces acting on the joint and degrades over time much research has focused on utilising tissue engineering strategies to yield a fully functional, long lasting repair tissue [46]. Tissue engineering is the persuasion of the body to heal itself through the delivery of cells, biomolecules and scaffolds [55]. Towards this goal, this research describes loading a collagen–glycosaminoglycan (CG) scaffold with bioactive molecules and cells to enhance articular cartilage regeneration within an in vitro model

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