Abstract
Polymeric membranes are widely applied in biomedical applications, including in vitro organ models. In such models, they are mostly used as supports on which cells are cultured to create functional tissue units of the desired organ. To this end, the membrane properties, e.g., morphology and porosity, should match the tissue properties. Organ models of dynamic (barrier) tissues, e.g., lung, require flexible, elastic and porous membranes. Thus, membranes based on poly (dimethyl siloxane) (PDMS) are often applied, which are flexible and elastic. However, PDMS has low cell adhesive properties and displays small molecule ad- and absorption. Furthermore, the introduction of porosity in these membranes requires elaborate methods. In this work, we aim to develop porous membranes for organ models based on poly(trimethylene carbonate) (PTMC): a flexible polymer with good cell adhesive properties which has been used for tissue engineering scaffolds, but not in in vitro organ models. For developing these membranes, we applied evaporation-induced phase separation (EIPS), a new method in this field based on solvent evaporation initiating phase separation, followed by membrane photo-crosslinking. We optimised various processing variables for obtaining form-stable PTMC membranes with average pore sizes between 5 to 8 µm and water permeance in the microfiltration range (17,000–41,000 L/m2/h/bar). Importantly, the membranes are flexible and are suitable for implementation in in vitro organ models.
Highlights
With increasing costs to develop new medicines and treatments, and ethical and scientific concerns related to the use of animal models, there is an increasing need for developing in vitro organ-mimicking models [1]
We describe the development of membranes for organ-on-chip (OoC) models based on the polymer poly(trimethylene carbonate) (PTMC), which is transparent [23], non-cytotoxic [29,30]
Based on earlier studies on PTMC-based scaffolds [31,37], we added poly(ethylene oxide) (PEO) as pore former and stabiliser in the PTMC dope, which led to porous membranes
Summary
With increasing costs to develop new medicines and treatments, and ethical and scientific concerns related to the use of animal models, there is an increasing need for developing in vitro organ-mimicking models [1] These models should generate more reliable results than traditional models, such as those based on cell cultures in dishes on tissue culture plastic and those in Transwell® inserts under static. Polymeric membranes are a vital part of many organ models [1,2,3,4,5,6,7,8,9,10] They provide a surface for the cells to attach and grow and often (partly) substitute the extracellular matrix (e.g., the basal membrane). The membranes used in organ models of dynamic tissues, such as the lung and heart, need to match the mechanical properties of these organs since these properties affect cellular behaviour [1]
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