Hydrogels

Harrick Plasma → Applications → Life Sciences → Biotechnology → Hydrogels

Hydrogels are hydrophilic, polymerized networks with high biocompatibility. Hydrogels trap water and other fluids, making them ideal for drug delivery, cell seeding, and tissue engineering applications. Hydrogel fabrication relies on plasma treatment to create pristine substrates for good hydrogel adhesion. Plasma treatment also is used for micropatterning hydrogels or bonding microfluidic devices which mix hydrogel precursors.

In this application note, you will learn about the many benefits of plasma treatment for developing robust and versatile hydrogels.

Micropatterning of Hydrogels

Researchers rely on micropatterned hydrogels to produce anatomically accurate morphologies of engineered tissue. A polymer stamp, usually made from polydimethylsiloxane (PDMS), is pressed into the hydrogel surface to form a micropattern. Plasma treating the stamp increases its hydrophilicity and removes contaminants that could adhere to the hydrogel.

Park et. al. used this process in their research of tooth regeneration. Methacrylated hyaluronic acid (MeHA) hydrogel acts as a cell scaffold for dental pulp stem cells (DPSCs), the initial components of tooth growth. To form the hydrogel into the shape of a developing tooth, Park et. al. created a microwell-shaped stamp from polydimethylsiloxane (PDMS) and plasma-treated it. Plasma treatment increased the hydrophilicity of the PDMS and allowed a MeHA solution to wet the stamp for microwell formation (Figure 1).

Figure 1: Microwell formation in a MeHA hydrogel using a plasma-treated PDMS stamp. Adapted from Park et. al.

Rexius-Hall et. al. used micropatterned hydrogel chips assembled using plasma treatment to accurately model skeletal muscle structure in 2D and prolong the lifetime of engineered myotubes. The authors plasma-treated polystyrene substrates to make them hydrophilic and covered them with a gelatin / microbial transglutaminase (MTG) hydrogel solution. Plasma treatment improved the attachment of the hydrogel to the polystyrene substrates. Next, the authors micropatterned the hydrogel using polydimethylsiloxane (PDMS) stamps. These hydrogel chips aligned the myotubes produced from C2C12 murine myoblasts to accurately model skeletal muscle structure in 2D.

Further information about the role of plasma treatment in hydrogel micropatterning can be found in the references below.

Plasma – Bonding PDMS Components for Hydrogel Studies

Hydrogels are often fabricated using microfluidic devices bonded via plasma treatment. These microfluidic devices frequently consist of a micro-channeled polydimethylsiloxane (PDMS) layer bonded to a glass slide. Plasma treatment introduces polar hydroxyl groups (-OH) to increase surface hydrophilicity. When plasma treated glass and PDMS are placed in contact, silanol groups react to form siloxane bridges (Si-O-Si) that provide a water-tight seal. The increased hydrophilicity of the PDMS channels improves the flow of hydrogel precursors during fabrication. For instance, Correa et. al. flowed a mixture of collagen and alginate into a microfluidic device to rapidly a form a dense collagen hydrogel. By adjusting the flow rate and concentration of alginate, the authors could tune the hydrogel thickness.

Lobban et. al. developed a microfluidic device to investigate the gel-to-sol transition of polymer hydrogels. These cooling-triggered reactions were tested by flowing a hydrogel into the plasma-bonded PDMS device and immersing the device in an ice bath.

PDMS plasma-bonding is also useful when preparing samples for confocal microscopy. Sanandiya et. al. bonded a polydimethylsiloxane (PDMS) mold to a glass coverslip using plasma treatment and injected a cellulose nanofiber (CNF) hydrogel into the mold. The molded hydrogel was then imaged using confocal microscopy.

To learn more about plasma bonding of PDMS components in hydrogel research, see the references listed below.

Plasma Cleaning for Microscopy Studies of Hydrogels

Researchers often use plasma treatment to clean microscopy components prior to imaging hydrogels. For example, plasma-cleaned Scanning Electron Microscopy (SEM) mounts provide pristine surfaces for spin-coated hydrogels. Plasma treating glass slides removes fluorescent contaminants that could introduce artifacts during Total Internal Reflection Fluorescence (TIRF) Microscopy. Atomic Force Microscopy (AFM) cantilevers and substrates can be functionalized using plasma treatment to promote accurate measurements of hydrogel adhesion forces. You can learn more about the role of Harrick Plasma’s plasma treatment equipment in these processes using the articles below.

Plasma Cleaning Substrates for Hydrogel Fabrication

Plasma treatment allows hydrogel adhesion to substrates with a variety of morphologies and compositions. For example, Liu et. al. plasma-cleaned substrates made of glass, metals, elastomers, and ceramics before dip-coating them in a polyvinylalcohol (PVA) hydrogel solution. These substrates ranged from tubes to optical fibers and springs. Plasma treatment removed organic contaminants for optimal hydrogel adhesion to the substrate.

Figure 2: Protocol to obtain amino acids from fingerprints. Adapted from Van Helmond et. al.

Plasma treatment of glass coverslips enabled Van Helmond et. al. to collect amino acids from fingerprints without damaging the ridge details of the prints (Figure 2). First, Van Helmond applied a fingerprint to a glass slide and covered it with a dextran-methacrylate (DEX-MA) hydrogel solution. Next, the authors plasma-cleaned a glass coverslip and functionalized it with 3-(trichlorosilyl)-propyl-methacrylate before placing it on top of the glass slide. Plasma cleaning activated the coverslip surface and removed organic contamination. After illumination of the glass slide / coverslip, a DEX-MA hydrogel formed between the two surfaces. Upon removal of the coverslip, the amino acids trapped in the hydrogel were analyzed via Ultra Performance Liquid Chromatography (UPLC).

In a preliminary research study, Parada et. al. relied on Harrick Plasma’s Expanded Plasma Cleaner to study the thrombosis-resistant properties of hydrogel-coated polyvinyl chloride (PVC) tubing. Parada treated the tubing with air plasma before submerging it in a benzophenone solution and then a hydrogel precursor solution (Figure 3). Plasma treatment removed organic contaminants from the inner and outer surfaces of the tube and provided a pristine surface for hydrogel formation. Blood clotting in the hydrogel-coated tubing dropped by a factor of two compared to blood clotting in non-coated tubing.

Figure 3: Hydrogel formation on the inner and outer surfaces of PVC tubing with the help of plasma treatment. Adapted from Parada et. al.

Learn more about the benefits of plasma treatment for cleaning substrates in the articles below.