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Experiments on the transport of radiolabeled Insulin-like Growth Factors (IGF-I and -II) into bovine articular cartilage show differential uptake depending on the relative proportion of IGF-I and -II. In this study, we present a mathematical model describing both the transport and competition of IGF-I and -II for binding sites represented by two functional groupings of IGF binding proteins (IGFBPs). The first grouping has approximately similar binding affinity to both IGF-I and -II (i.e. IGFBPs 1–5), whereas the second group has significantly higher binding preference for IGF-II compared to IGF-I (i.e. IGFBP-6). Using nonlinear least squares, it is shown that the experimental equilibrium competitive binding results can be described using a reversible Langmuir sorption isotherm involving two dominant IGFBP functional groups.
After coupling the sorption model with a poromechanical continuum model, parametric studies are carried out to investigate the effect of model changes including IGF boundary conditions and the ratios of the two IGFBP functional groups. The results show that ignoring competitive binding leads to a significant overestimation of total IGF-I uptake, but an underestimation the rate of "free" (physiologically active) IGF-I within the cartilage. An increase of first group of IGFBPs (i.e. IGFBPs 1–5) as has been reported for osteoarthritis, is observed to hinder the bioavailability of free IGF-I in cartilage, even though the total IGF-I uptake is enhanced. Furthermore, the combination of dynamic compression and competitive binding is seen to enhance the IGF-I uptake within cartilage, but this enhancement is overestimated if competitive binding is neglected.
Cartilage injuries may be caused by trauma, biomechanical imbalance, or degenerative changes of joint. Unfortunately, cartilage has limited capability to spontaneous repair once damaged and may lead to progressive damage and degeneration. Cartilage tissue-engineering techniques have emerged as the potential clinical strategies. An ideal tissue-engineering approach to cartilage repair should offer good integration into both the host cartilage and the subchondral bone. Cells, scaffolds, and growth factors make up the tissue engineering triad. One of the major challenges for cartilage tissue engineering is cell source and cell numbers. Due to the limitations of proliferation for mature chondrocytes, current studies have alternated to use stem cells as a potential source. In the recent years, a lot of novel biomaterials has been continuously developed and investigated in various in vitro and in vivo studies for cartilage tissue engineering. Moreover, stimulatory factors such as bioactive molecules have been explored to induce or enhance cartilage formation. Growth factors and other additives could be added into culture media in vitro, transferred into cells, or incorporated into scaffolds for in vivo delivery to promote cellular differentiation and tissue regeneration.
Based on the current development of cartilage tissue engineering, there exist challenges to overcome. How to manipulate the interactions between cells, scaffold, and signals to achieve the moderation of implanted composite differentiate into moderate stem cells to differentiate into hyaline cartilage to perform the optimum physiological and biomechanical functions without negative side effects remains the target to pursue.
Maintenance of differentiated functional phenotype within in vitro chondrocyte culture requires seeding at high densities with large numbers of cells. However, optimal cell seeding numbers and densities remain elusive due to multiple varying parameters and different methodologies utilized in previous studies. In the current study, we tried to investigate the relationship between cell seeding number and differentiated functional phenotype of in vitro cultured chondrocytes. Varying numbers of primary porcine chondrocytes (0.25, 2.5, 25 and 250 K) were seeded in 96 well-plates and cultured for 4 weeks. Cell proliferation, glycosaminoglycan (GAG) production and gene expression levels of Sox9, aggrecan, COL II and COL I were evaluated. The results showed that GAG content was high in the 0.25 and 25 K groups, gene expression of Sox9 was high in the 2.5, 25 and 250 K groups and expression of COL II was high in the 25 K group, whereas expression of COL I was low in the 0.25, 25 and 250 K groups. It is concluded that the seeding number and density of the 25 K (78 K cells/cm2) group achieved the optimal balance between functional phenotype of individual cells and the total ECM production for in vitro cultured chondrocytes.