Cell Seeding Process Experiment and Simulation on Three-Dimensional Polyhedron and Cross-Link Design Scaffolds.

Ziyu Liu,Nan Xu,Yingying Gu,Maryam Tamaddon,Chaozong Liu,Fangli Gang,Jianshu Yu,Xiaodan Sun

doi:10.3389/fbioe.2020.00104

Abstract

Cell attachment to a scaffold is a significant step toward successful tissue engineering. Cell seeding is the first stage of cell attachment, and its efficiency and distribution can affect the final biological performance of the scaffold. One of the contributing factors to maximize cell seeding efficiency and consequently cell attachment is the design of the scaffold. In this study, we investigated the optimum scaffold structure using two designs – truncated octahedron (TO) structure and cubic structure – for cell attachment. A simulation approach, by ANSYS Fluent coupling the volume of fluid (VOF) model, discrete phase model (DPM), and cell impingement model (CIM), was developed for cell seeding process in scaffold, and the results were validated with in vitro cell culture assays. Our observations suggest that both designs showed a gradual lateral variation of attached cells, and live cell movements are extremely slow by diffusion only while dead cells cannot move without external force. The simulation approaches supply a more accurate model to simulate cell adhesion for three-dimensional structures. As the initial stages of cell attachment in vivo are hard to observe, this novel method provides an opportunity to predict cell distribution, thereby helping to optimize scaffold structures. As tissue formation is highly related to cell distribution, this model may help researchers predict the effect of applied scaffold and reduce the number of animal testing.

Highlights

IntroductionFinal tissue formation is strongly related to initial cell attachment (Wendt et al, 2006; Santoro et al, 2010)
In regenerative approaches, final tissue formation is strongly related to initial cell attachment (Wendt et al, 2006; Santoro et al, 2010)
The lack of information about the cell attachment is especially pronounced for larger 3D structures such as scaffolds, since examination facilities for cell adhesion and spatial distribution are generally only available for 2D surfaces or thinner 3D structures

Summary

Introduction

Final tissue formation is strongly related to initial cell attachment (Wendt et al, 2006; Santoro et al, 2010). Preceding all other steps of tissue engineering, a better cell adhesion and an even spatial distribution are associated with improved culture results (Olivares and Lacroix, 2012). This is one of the determinants of the final bio-performance of a scaffold, it is difficult to observe the cell seeding process and cell distribution within the scaffold during the seeding process. There are some contradictory parameters in scaffold design including the pore size with surface area, porosity with strength, and fatigue life, which lead to a complex assessment of the scaffold design and an increase in the number of in vivo tests for design optimization

Methods

Findings

Discussion

Conclusion