title: Quantitative analysis of exogenous IGF-1 administration of intervertebral disc through intradiscal injection.
abstract: 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.
authors.affiliation: Stem Cell and Mechanobiology Lab, Dept of Biomedical Engineering, University of Miami, Coral Gables, Florida 33146, USA.
authors.forename: C-Y
authors.initials: CY
authors.lastname: Huang
authors.forename: F
authors.initials: F
authors.lastname: Travascio
authors.forename: W Y
authors.initials: WY
authors.lastname: Gu
mesh_terms: D001696:Biomechanical Phenomena; D020342:Finite Element Analysis; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007267:Injections; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D007403:Intervertebral Disc / Q000187:drug effects* / Q000378:metabolism; D055959:Intervertebral Disc Degeneration / Q000188:drug therapy* / Q000378:metabolism; D019344:Lactic Acid / Q000096:biosynthesis; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D011485:Protein Binding; D014018:Tissue Distribution
chemical_list: D019344:Lactic Acid; D007334:Insulin-Like Growth Factor I; D005947:Glucose