PDMS leaching and its implications for on-chip studies focusing on bone regeneration applications

Carter, Sarah‐Sophia D.; Atif, Abdul-Raouf; Kadekar, Sandeep; Lanekoff, Ingela; Engqvist, Håkan; Varghese, Oommen P.; Tenje, Maria; Mestres, Gemma

doi:10.1016/j.ooc.2020.100004

Cited by 52 publications

(48 citation statements)

References 26 publications

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“…34,37 Particularly, in our recent work it was shown that PDMS oligomers enhanced the differentiation of MC3T3-E1 preosteoblast-like cells. 38 Whereas the Ti-PDMS-chip comes with the advantage of reusing several of the fabricated components (i.e. silicon master mold and additively manufactured fixture), specialized equipment and a cleanroom setting are required.…”

Section: Discussionmentioning

confidence: 99%

Exploring microfluidics as a tool to evaluate the biological properties of a titanium alloy under dynamic conditions

2020

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Section: Discussionmentioning

confidence: 99%

Exploring microfluidics as a tool to evaluate the biological properties of a titanium alloy under dynamic conditions

2020

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“…PDMS (Sylgard 184) membranes are commonly used in cell-stretch devices due to their mechano-elastic properties. However, it has been reported that uncured oligomers of PDMS are released into the culture medium during cell culture, which might be toxic for the cells (Regehr et al, 2009 ; Carter et al, 2020 ). Hence, we assessed the leaching of unwanted components of the PDMS membrane compared to the (optimum) BETA membrane ( Figure 3C ).…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, PDMS membranes have low wettability (WCA ≥ 115°) ( Supplementary Figure 1 ) and therefore require pre-treatment and/or coating with ECM proteins to facilitate sufficient cell adhesion and proliferation (Wang et al, 2010 ). Another disadvantage is that uncured oligomers of PDMS can leach into the cell culture medium resulting in changes and cell physiology (Regehr et al, 2009 ; Carter et al, 2020 ). Our investigation of a PDMS film has confirmed reports from the literature that cells may experience reduced cell viability due to the leaching of toxins into the cultured in a medium (Regehr et al, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

A Bioinspired in vitro Lung Model to Study Particokinetics of Nano-/Microparticles Under Cyclic Stretch and Air-Liquid Interface Conditions

Doryab

Taskin

Stahlhut

et al. 2021

Front. Bioeng. Biotechnol.

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Evolution has endowed the lung with exceptional design providing a large surface area for gas exchange area (ca. 100 m2) in a relatively small tissue volume (ca. 6 L). This is possible due to a complex tissue architecture that has resulted in one of the most challenging organs to be recreated in the lab. The need for realistic and robust in vitro lung models becomes even more evident as causal therapies, especially for chronic respiratory diseases, are lacking. Here, we describe the Cyclic InVItroCell-stretch (CIVIC) “breathing” lung bioreactor for pulmonary epithelial cells at the air-liquid interface (ALI) experiencing cyclic stretch while monitoring stretch-related parameters (amplitude, frequency, and membrane elastic modulus) under real-time conditions. The previously described biomimetic copolymeric BETA membrane (5 μm thick, bioactive, porous, and elastic) was attempted to be improved for even more biomimetic permeability, elasticity (elastic modulus and stretchability), and bioactivity by changing its chemical composition. This biphasic membrane supports both the initial formation of a tight monolayer of pulmonary epithelial cells (A549 and 16HBE14o−) under submerged conditions and the subsequent cell-stretch experiments at the ALI without preconditioning of the membrane. The newly manufactured versions of the BETA membrane did not improve the characteristics of the previously determined optimum BETA membrane (9.35% PCL and 6.34% gelatin [w/v solvent]). Hence, the optimum BETA membrane was used to investigate quantitatively the role of physiologic cyclic mechanical stretch (10% linear stretch; 0.33 Hz: light exercise conditions) on size-dependent cellular uptake and transepithelial transport of nanoparticles (100 nm) and microparticles (1,000 nm) for alveolar epithelial cells (A549) under ALI conditions. Our results show that physiologic stretch enhances cellular uptake of 100 nm nanoparticles across the epithelial cell barrier, but the barrier becomes permeable for both nano- and micron-sized particles (100 and 1,000 nm). This suggests that currently used static in vitro assays may underestimate cellular uptake and transbarrier transport of nanoparticles in the lung.

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“…PDMS has been widely used in the fabrication of microfluidic devices, including MPS. However, PDMS usage has been associated with problems in cell culture and applications in drug development and disease modeling (Berthier et al, 2012;Carter et al, 2020;Toepke and Beebe, 2006;van Meer et al, 2017). Among these problems, absorption of the hydrophobic molecules is critical for drug development and disease modeling.…”

Section: Discussionmentioning

confidence: 99%

“…However, MPS platforms still have some issues to be addressed, particularly those based on polydimethylsiloxane (PDMS), which has often been used in the fabrication of MPS platforms owing to its biocompatibility, gas permeability, and transparency. Since PDMS also exhibits hydrophobicity and porosity, which allows chemical/drug absorption, water evaporation, deformation, and leaching of un-crosslinked reagents (Berthier et al, 2012;Carter et al, 2020;Toepke and Beebe, 2006;van Meer et al, 2017), PDMS-based MPSs have limited applications owing to the undesired influence of the cellular responses (Kamei et al, 2013). In particular, to establish in vitro NAFLD models, the absorption of hydrophobic molecules is considered a critical property because the key molecules for NAFLD modeling, such as free fatty acids (FFAs), are absorbed into the PDMS material to reduce the amount of FFAs in the cell-culture media.…”

Section: Introductionmentioning

confidence: 99%

In vitrononalcoholic fatty liver disease model with cyclo-olefin-polymer-based microphysiological systems

Wen

Yamanaka

Terada

et al. 2020

Preprint

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Nonalcoholic fatty liver disease (NAFLD) is one of the common chronic liver conditions, whose treatment involves curing patients without liver transplantation. Understanding the mechanism of NAFLD initiation and progression would enable development of new diagnostic tools and drugs; however, until now, the underlying mechanisms of this condition remain largely unknown owing to the lack of experimental settings that can simplify the complicated NAFLD process in vitro. Microphysiological systems (MPSs) have long been used to recapture human pathophysiological conditions in vitro for applications in drug discovery. However, polydimethylsiloxane (PDMS) has been used in most of these MPSs as the structural material; it absorbs hydrophobic molecules, such as free fatty acids (FFAs), which are the key components that initiate NAFLD. Therefore, the current PDMS-based MPSs cannot be directly applied to in vitro NALFD modeling. In this work, we present an in vitro NAFLD model with an MPS made of cyclo-olefin polymer (COP), namely COP-MPS, to prevent absorption of FFAs. We demonstrated induction of the NAFLD-like phenotype in HepaRG hepatocyte-like cells cultured in the COP-MPS by introducing FFAs. The FFAs induced lipid accumulation in the HepaRG cells, resulting in inactivation of the apoptotic cells. We believe that the proposed COP-MPS can contribute toward investigations of NAFLD mechanisms and identification of new drugs to prevent the progression of liver disease and avoid liver transplantation.

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PDMS leaching and its implications for on-chip studies focusing on bone regeneration applications

Cited by 52 publications

References 26 publications

Exploring microfluidics as a tool to evaluate the biological properties of a titanium alloy under dynamic conditions

Exploring microfluidics as a tool to evaluate the biological properties of a titanium alloy under dynamic conditions

A Bioinspired in vitro Lung Model to Study Particokinetics of Nano-/Microparticles Under Cyclic Stretch and Air-Liquid Interface Conditions

In vitrononalcoholic fatty liver disease model with cyclo-olefin-polymer-based microphysiological systems

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