Analysis of Collagen and Glucose Modulated Cell Growth within Tissue Engineered Scaffolds

Abstract

The strategy of tissue engineering includes seeding cells onto porous scaffolds. The cellular construct is cultured in vitro for a period of time before transplantation for the patient. Because of the intrinsic complexity of biological systems, it is valuable to have models of simulation that can assess the culture conditions and optimize experiments. This work presents a mathematical model to account for the effects of glucose and type II collagen on chondrocyte growth under static culture conditions. Dependence of cell growth on collagen was assumed as a biphasic function of collagen quantity, whereby the cell growth rate increases and then decreases with increasing collagen content. Results from simulation were compared with experimental data in literature. The model was then applied to investigate the effects of cell seeding area, demonstrating the spatiotemporal evolution of cell distribution in scaffolds. Results show that the conventional uniform seeding method may not be a good way of gaining uniform and large cell number densities at the final stage of cultivation. A seeding mode that has cells reside initially in the middle area of scaffold was shown to be able to not only reduce the diffusion limitation of nutrients but also weaken the inhibiting impact of aggregated collagen on cell growth. Therefore the middle seeding mode may result in better cell amounts and uniformities for developing tissue engineered constructs.

Synthesis rates and binding kinetics of matrix products in engineered cartilage constructs using chondrocyte-seeded agarose gels

“…The model presented here extends previous models that have examined ECM synthesis and nutrient consumption (Chung and Ho, 2010; Dimicco and Sah, 2003; Nikolaev et al, 2010; Obradovic et al, 2000; Sengers et al, 2004a; Sengers et al, 2004b, 2005; van Donkelaar et al, 2011). In the model employed here, glucose was selected as the limiting nutrient.…”

Prediction of cell growth rate over scaffold strands inside a perfusion bioreactor

“…Figure 6a, b shows the steady-state glucose concentration distribution for a Schmidt number of Sc = 1,000 for s = 4R and s = 3R, respectively. An adequate supply of glucose is also required for the growth of cells, especially for the Chondrocytes growth (Chung and Ho 2010). In general, the distributions of the glucose concentration contours are very similar to those given in Fig.…”

A multiscale modeling approach to scaffold design and property prediction

“…The design of the scaffold has been motivated by results in the literature which indicated that cell growth in scaffolds may be significantly limited by nutrient delivery as the void space inside the scaffolds is gradually occupied by cells, thereby restricting nutrient transport to the interior of the scaffold (Freed et al, 1994). Recent work by Chung and Ho (2010) suggests that internal seeding of cells in the interior of a scaffold may lead to better cell amounts and uniformities within the scaffold. The smaller diameter of the interconnecting channels may be varied to promote cell adhesion (Green et al, 2002;, while the larger pore diameter in the interior region of the scaffold may be optimized to promote cell migration and proliferation .…”