Stem Cell and Mechanobiology Lab, Dept of Biomedical Engineering, University of Miami, Coral Gables, Florida 33146, USA.
J Biomech. 2012 Apr 30;45(7):1149-55. doi: 10.1016/j.jbiomech.2012.02.005. Epub 2012 Feb 25.
Exogenous administration of IGF-1 has been proposed as a therapy for disc degeneration. The objectives of this study were to develop a numerical model for quantitatively analysing exogenous administration of IGF-1 into the intervertebral disc (IVD) via intradiscal injection and to investigate the effects of IGF-1 administration on distribution of glucose and oxygen in the IVD. In this study, the reversible binding reaction between IGF-1 and IGF binding proteins was incorporated into the mechano-electrochemical mixture model. The model was used to numerically analyse transport of IGF-1, glucose, oxygen and lactate in the IVD after IGF-1 administration. The enhancement of IGF-1 on lactate production was also taken into account in the theoretical model. The numerical analyses using finite element method demonstrated that the binding reactions significantly affect the time-dependent distribution of IGF-1 in the IVD. It was found that the region affected by IGF-1 was smaller and the duration of the therapeutic IGF-1 level was longer in the degenerated disc with a higher concentration of IGF binding proteins. It was also found that the IGF-1 injection can reduce glucose concentration and increase lactate accumulation (i.e., lower pH) in the IVD and these influences were regulated by the IGF-1 binding reactions. This study indicated the complexity of intradiscal administration of growth factors, which needs to be fully analysed in order to achieve a successful outcome. The new theoretical model developed in this study can serve as a powerful tool in analysing and designing the optimal treatments of growth factors for disc degeneration.
外源性 IGF-1 的给药被提议作为治疗椎间盘退变的一种方法。本研究的目的是开发一个数值模型，用于定量分析通过椎间盘内注射将 IGF-1 递送到椎间盘（IVD）中的情况，并研究 IGF-1 给药对 IVD 中葡萄糖和氧气分布的影响。在本研究中，将 IGF-1 与 IGF 结合蛋白之间的可逆结合反应纳入到机械电化学混合模型中。该模型用于数值分析 IGF-1 给药后 IGF-1、葡萄糖、氧气和乳酸在 IVD 中的传输。理论模型还考虑了 IGF-1 对乳酸生成的增强作用。使用有限元方法的数值分析表明，结合反应显著影响 IGF-1 在 IVD 中的时变分布。研究发现，在具有更高 IGF 结合蛋白浓度的退变椎间盘中，受 IGF-1 影响的区域更小，治疗性 IGF-1 水平的持续时间更长。还发现 IGF-1 注射可以降低 IVD 中的葡萄糖浓度并增加乳酸积累（即 pH 值降低），而这些影响受 IGF-1 结合反应的调节。本研究表明了生长因子椎间盘内给药的复杂性，需要进行全面分析才能取得成功。本研究中开发的新理论模型可以作为分析和设计椎间盘退变生长因子最佳治疗方法的有力工具。
