Large Molecular-Weight Solute (40 kDa) Entangles the Transport of Medium One (4 kDa) within Intervertebral Disc

INTRODUCTION: Solute transport within the intervertebral disc is critical for the disc functions. Small molecular-weight solutes, such as glucose, lactate and oxygen, are the components of the nutrient supply and the metabolic waste removal. Molecular weight of enzymes and chemical drugs for the disc therapy are usually within the order of thousands of Dalton. Larger solutes such as cytokines (10-40 kDa), morphogens and protease (30-90 kDa) are critical to regulate the cellular process and disc biological functions. The solute transport within the disc is affected by the molecular size, interstitial space of extracellular matrix and the driving pressure. It is understood that the small solute transport within the disc is dominated by the diffusion, and the larger solute transport can be helped by the convection. The disc imbibes and expels the fluid during diurnal loading. The dynamic external loading, which is practically the origin of driving pressure of disc fluid, increases fluid flow rate within the disc; hence increase the solute transport. Many emerging researches used large molecules (such as morphogens and proteases) or drug delivery vehicles (such as microsomes or liposomes) for disc therapy. To warrant the delivery of these particles, the confounding effects between molecular size, interstitial space and driving pressure are needed to be cleared. For example, does the larger molecular-weight solute retard the transport of smaller molecular-weight solute? Does the dynamic repetitive loading increase the solute transport than the static creep loading does? The purpose of this study is to answer these questions by evaluating the solute transport of fluorescent reagent of small (0.4 kDa), medium (4.4 kDa), and large molecule (40 kDa) under no load, 1 hr creep and 0.5 hr fatigue loading.