Development of a laser foaming process for high throughput three-dimensional tissue model devices

Ock, JinGyu
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A three-dimensional (3D) porous structure on biodegradable or biocompatible polymers have attracted tremendous attention in numerous bio-related areas including 3D cell culturing and tissue engineering because of their microenvironment similar to ones in vivo. In this study, a novel fabrication process, named selective laser foaming, was developed to create localized 3D porous structure on a polymer chip. The effects of laser power and lasing time on the porous structure were studied both experimentally and through finite element modeling. A high throughput two-chamber tissue model platform was developed using the proposed selective laser foaming process. For comparison, cell culture studies were conducted with both selective laser foamed and unfoamed polylactic acid (PLA) samples using T98G cells. The results show that by laser foaming gas-impregnated polylactic acid it is possible to generate an array of inverse cone-shaped wells with porous walls. The size of the foamed region can be controlled with laser power and exposure time, while the pore size of the scaffold can be manipulated with the saturation pressure. The finite element modeling results showed good agreement with the experimental data; therefore, the model could be used to optimize and control the selective foaming process. T98G cells grew well in the foamed scaffolds, forming clusters that have not been observed in 2D cell cultures. Cells were more viable in the 3D scaffolds than in the 2D cell culture cases, suggesting that the 3D porous microarray could be used for parallel studies of drug toxicity, guided stem cell differentiation, and DNA binding profiles. As an example, a high-throughput two-chamber 3D tissue model platform driven by the centrifugal force was developed for drug screening. The selective laser foaming process was calibrated to fabricate 3D scaffold on a commercially available compact disc (CD) made of polycarbonate (PC). Laser foaming of gas saturated polycarbonate created inverse cone-shaped wells with micro-sized porous structure underneath the surface. The open pores were hundreds of micrometers in diameter and depth. The pore size of the underneath porous structure was several tens of micrometers. The size of the well was dependent on the laser power and laser exposure time. Two laser-foamed scaffolds were fabricated in tandem and two mechanically-machined chambers were placed adjacent to the scaffolds, respectively. All scaffolds and chambers were in line and all of them were connected with micro-channels. The surface was coated with polydopamine (PDA) in order to increase the hydrophilicity and biocompatibility. After sterilization, human glioblastoma multiforme (M059K) and hepatoblastoma (C3A sub28) were seeded in the two 3D scaffolds separately and cultured for up to four weeks. These cells grew well in the scaffolds and cell aggregates were observed, suggesting that the developed two-chamber tissue model array could be useful for high-throughput biochemical assays.