Fabricating porous, photo‐crosslinked poly(trimethylene carbonate) membranes using temperature‐induced phase separation

Abstract

The recent development of lungs‐on‐chips is a major advancement in lung disease research. However, the materials used for the membranes in these chips, e.g. poly(dimethyl siloxane) and silicon, are not ideal. This study uses the more biocompatible and mechanically favorable polymer poly(trimethylene carbonate) (PTMC). Porous membranes were made of high molecular weight linear PTMC (250,000 g/mol) via temperature‐induced phase separation with ethylene carbonate, followed by ultraviolet (UV)‐light crosslinking with pentaerythritol triacrylate and Irgacure 2959. Membrane morphology and crosslinking efficacy was investigated. Membranes with micrometer‐sized pores could be made. There was variation between the different membrane sides in terms of pore size and distribution. Cooling during UV‐light crosslinking resulted in more homogeneous membrane pores, both in size and distribution, and raised the gel content from 48% to 73%, which can be further enhanced by adjustment of the UV treatment or the amount of crosslinking agents. All membranes were highly permeable to water suggesting that nutrient transport, when used with cells, is not limited by the membranes. Here, we show the development of thin and porous PTMC membranes for lungs‐on‐chips, Transwell® inserts and other cell culturing applications. Copyright © 2016 John Wiley & Sons, Ltd.

Evolution of Bioengineered Lung Models: Recent Advances and Challenges in Tissue Mimicry for Studying the Role of Mechanical Forces in Cell Biology

“…For in vitro cell cultures, size and topography of the pores in the membrane need to be large enough to achieve desirable gas and nutrient exchange between apical and basal compartment (at least 10 nm diameter for large biomolecules to pass through), but small enough to prevent inadvertent cell migration across the membrane (<3–8 µm depending on cell type). Hence, the most widely used pore size of ≈3 µm facilitates the formation of epithelial‐endothelial cell bilayers mimicking the alveolar‐capillary barrier, while allowing transport of nutrients, growth factors and cell signaling molecules (e.g., cytokines, chemokines, and extracellular vehicles) at physiologic rates . Another major factor in mimicking the properties of the air–blood barrier of the lung is its thickness ≈0.6 µm in the gas exchange region .…”

Development of Porous and Flexible PTMC Membranes for In Vitro Organ Models Fabricated by Evaporation-Induced Phase Separation

“…Moreover, the permeances were high for membranes with a rather low porosity of 21.1-41.5%. The relatively low porosities and pore sizes of our membranes may stimulate cells to grow in proper confluent cell layers and thus create better barriers compared to membranes or scaffolds with much higher porosities and pore sizes [32,43,44], which may discourage cell-cell contact.…”

“…Earlier studies implemented temperature-induced phase separation (TIPS) [43] for the fabrication of porous PTMC membranes and liquid-induced phase separation (LIPS) [31] for porous PTMC scaffolds. However, the fabrication of membranes by TIPS was not reproducible [43]. LIPS resulted in reproducible PTMC scaffolds for cell culture, which could be crosslinked by gamma-irradiation.…”

Photo-crosslinked synthetic biodegradable polymer networks for biomedical applications

“…Conventional techniques used to fabricate tissue engineering scaffolds include solvent casting, particulate porogen leaching, phase separation, membrane lamination, melt molding, injection molding and freeze drying [119,120,124]. Several of these techniques have also been used to prepare photo-crosslinked porous structures [125][126][127]. For example, porous tubular scaffolds for vascular tissue engineering have been prepared by photo-crosslinking a mixture of photo-crosslinkable PTMC macromers and salt particles, followed by leaching of the salt [125].…”

“…For example, porous tubular scaffolds for vascular tissue engineering have been prepared by photo-crosslinking a mixture of photo-crosslinkable PTMC macromers and salt particles, followed by leaching of the salt [125]. Porous photocrosslinked scaffolds have also been prepared by employing temperature-induced phase separation [126,127]. Upon cooling macromer solutions ethylene carbonate (a crystallizable solvent), subsequent photo-crosslinking of the matrix and extraction of the dispersed ethylene carbonate crystals with water, a porous photo-crosslinked structure is obtained.…”