Chemical and physical modifications to poly(dimethylsiloxane) surfaces affect adhesion of Caco‐2 cells

Abstract

Polydimethylsiloxane (PDMS) silicone elastomer is extensively used in soft lithography processes to fabricate microscale or nano scale systems for microfluidic or cell culture applications. Though PDMS is biocompatible, it is not an ideal material for cell culture due to its poor cell adhesion properties. In this study, PDMS surfaces were modified to promote intestinal cell adhesion, in the interest of testing feasibility of using microfabricated PDMS systems for high throughput drug screening. Modification techniques included changing chemical composition of PDMS (i.e., varying curing to mixing agent ratio, and oxidization of PDMS surface by oxygen plasma), surface treatment of PDMS by coating with charged molecules (i.e., poly-D-lysine, L-alpha-phosphatidylcholine, and a layer bylayer coating), and deposition of extracellular matrix (ECM) proteins (i.e., laminin, fibronectin, and collagen). The influence of these modifications on PDMS properties, including elastic modulus and surface properties (wettability, chemical composition, topography, and protein adsorption) were characterized. Modification techniques were all found to change PDMS properties and influence the attachment and proliferation of Caco-2 cells over three days of culture to varying degrees. Generally, Caco-2 cells preferred to attach on collagen-coated, fibronectin-coated, and fibronectin-coated oxygen-plasma treated PDMS. The results highlight the importance of considering multiple physical and chemical factors that may be influenced by biomaterial modification and result in altered cell attachment to microfabricated systems, including surface hydrophobicity, chemical composition, stiffness, and topography. This study provides a foundation for further miniaturization, utilizing soft lithography techniques, of Caco-2 cell-based system for high-throughput screening of drug intestinal absorption during lead optimization in drug discovery. The understanding of different surface modifications on adjusting cell adhesion on PDMS allows systemic design of Biomicroelectromechanical Systems (BioMEMS) with tunable cell adhesion properties.

Effect of varying mixing ratio of PDMS on the consistency of the soft-contact Stribeck curve for glycerol solutions

“…Although the general trend that smaller ratio leads to lower PDMS modulus is in agreement with [25], it is interesting that 1:10 PDMS shows lower modulus than 1:8 PDMS as 1:10 is the manufacturer's recommended mixing ratio. Other studies show that a disproportionality in the mixing ratios beyond 1:10 also leads to lower values [27] or a plateau in Young's modulus [35].…”

“…Typically, a synthesis is carried out by mixing a curing agent and a base at 1:10 (w/w) and curing either at room temperature or in an oven at elevated temperatures for one hour to a few days. Increasing the concentration of curing agent relative to base can alter the surface properties in a few aspects, namely the rootmean-square (RMS) surface roughness [24,25], Young's modulus [24][25][26], and chemical composition [25], that affect lubrication behavior. In addition to the mixing ratio, curing time and temperature [27] and oxygen plasma treatment [21] also play an important role in determining the final surface properties.…”

Biomimetic modified clinical-grade POSS-PCU nanocomposite polymer for bypass graft applications: A preliminary assessment of endothelial cell adhesion and haemocompatibility

“…Although, hydrophobic substrates with low surface energies, do not promote EC adhesion, extremely hydrophilic substrates do not promote adhesion either. Surfaces with moderate hydrophilicity were found the highest levels cell adhesion [40]. According to the previous observations, θ of 55°showed the highest cell adhesion, meanwhile extremely hydrophobic and hydrophilic surfaces did not show much cell adhesion in comparison [16].…”

Star-shaped polyhedral oligomeric silsesquioxane-polycaprolactone-polyurethane as biomaterials for tissue engineering application

“…Another cell line, Mb231-GFP, was also observed to form a confluent layer on the starshaped POSS-PCL-PU film (Supplementary Figure S3). However, it is the presence of POSS in PCL-PU that improves the cell-substrate affinity because the moderate hydrophilicity provides a good support for the cell adhesion, 30 and the intrinsic roughness at sub-micrometer/ nanometer scales enhances the contact guidance for cell interactions and growth. 31 All these favorable factors (excellent biocompatibility, high porosity, moderate hydrophilicity and rough surface nanotopography) present in the star-shaped POSS-PCL-PU film created a very conducive environment for enhanced cell interactions, adhesion and proliferation.…”