Growth Factor Therapy for Degenerated Intervertebral Disc: Quantitative Analysis of Protocols for Exogenous Administration of IGF-1 Through Intradiscal Injection

INTRODUCTION The homeostasis of the intervertebral disc (IVD) is regulated by a delicate balance between catabolic and anabolic cellular processes. Unbalanced metabolic activity leads to the degeneration of the IVD tissue [1]. Several growth factors are known to up-regulate the anabolic activity of disc cells (e.g., TGF-, IGF, BMPs, etc.) [1]. In particular, it has been reported that IGF-1 stimulates the production of proteoglycans (PG) composing the extracellular matrix (ECM) of IVD [2,3]. Therefore, the exogenous administration of IGF-1 has been proposed as a therapy for disc regeneration [2]. Since cell response to IGF-1 stimulation is dose-dependent [3], knowledge and control of the distribution of this molecule in IVD is crucial for the success of the therapy. However, molecular transport in IVD is very complex and involves a series of coupled mechano-electrochemical events. In particular, transport of IGF1 is characterized reversible binding reactions with binding sites (mainly IGFBP-3) present on the ECM of cartilaginous tissues [4,5]. The complexity of this problem requires the aid of a numerical tool. The objective of this study was to investigate on therapeutic treatments for disc degeneration by quantitatively analyzing protocols of exogenous administration of IGF-1 to IVD via intradiscal injections. This was accomplished by developing a numerical model able to predict the timedependent distribution of IGF-1 in IVD during and after intradiscal infusions.