The promise of liquid crystals for biomedicine


July 19, 2023

(Nanowerk Highlights) Liquid crystal (LC) is a different state of matter that exhibits properties between a crystalline solid and an isotropic liquid. Their partially ordered structures give rise to unique characteristics that have recently shown promise for diverse biomedical applications.

LC can be categorized based on the mechanism of its formation. Thermotropic LC forms as temperature changes. They switch from the solid state to the LC state at the melting point as the crystals melt, and from the LC state to the isotropic liquid state at the clearing point because regularity is lost with increasing temperature. LC Lyotropic requires the presence of a solvent to form. They consist of amphiphilic molecules such as lipids that self-assemble into nanostructured phases such as hexagonal, cubic, and lamellar at certain concentrations, driven by hydrophobic and hydrophilic interactions.

The components that make up LC range from biological materials such as DNA, cellulose, collagen, chitin and silk fibers, to synthetic mesogenic molecules, polymer liquid crystals, and nanomaterials such as carbon nanotubes and graphene oxide sheets.

LC can be organized into phases with different degrees of order, such as a nematic phase in which rod-shaped molecules are aligned but not positionally arranged, a smectic phase with a layered structure, and a nematic or chiral cholesteric phase in which molecules are arranged in layers of twisted helices that selectively reflect light. Overview of liquid crystal materials for biomedical applications Overview of liquid crystal materials for biomedical applications. (Reprinted with permission by Wiley-VCH Verlag)

Recent review article on Advanced Materials (“Liquid Crystal Materials for Biomedical Applications”) summarizes the recent advances of LC materials for biomedical applications as shown in the illustration above.

Several key properties of LCs underlie their promise for biomedical use. LC exhibits optical anisotropy and birefringence due to the difference in refractive indices parallel and perpendicular to the director’s axis. This allows control over the transmission and reflection of light.

Cholesteric LC produces brilliant structural colors due to periodic helix twists. This makes LC useful as a bioimaging agent and optical reporter. LC also has a direction-dependent thermal conductivity, with heat transfer inside the plane being higher than outside the plane. This allows precise control over the thermal pathways in LC materials.

Another important feature is their excitability-responsiveness – LCs can change sequences or phase transitions in response to temperature, light, electric, or magnetic fields. This allows reversible transitions between the opaque and translucent states, or the nematic and isotropic phases.

Furthermore, polymeric LCs can exhibit macroscopic actuation and shape changes driven by changes in molecular sequence. This is particularly advantageous for soft robotics applications that mimic biological muscle movements. By rational molecular design, LC can be engineered to be biocompatible and biodegradable for safe interaction with human tissues.

One of the main biomedical application areas for LC is advanced drug delivery systems. Lyotropic LC nanostructures such as hexosomes and cubosomes provide a high loading capacity for hydrophobic, hydrophilic and amphiphilic drugs due to their compartmentalized internal domains. LC delivery vehicles protect sensitive drugs from degradation in transit and enable sustained or triggered release at target sites. By tuning the LC phase transition behavior using temperature or pH, researchers have developed intelligent systems for controlled drug release. LC has also been used to safely package and transport fragile genetic material such as DNA and RNA, which holds great promise for gene therapy.

LC also shows promise as a bioimaging agent and contrast enhancer. Inclusion of magnetic nanoparticles in LC creates an MRI contrast agent with enhanced relaxation compared to free nanoparticles. Lyotropic LC nanoparticles made from food-grade lipids and loaded with nitroxide radicals have been used for T1-weighted MRI in animal models. Fluorescent lyotropic LC nanocarriers have also been developed for cell imaging and tracking applications. The nanostructured domains help limit and stabilize the imaging payload.

In the field of tissue engineering, LC polymer networks and hydrogels have been explored as dynamic scaffolds to support cell adhesion, growth and differentiation. LC orientation and anisotropy sequences can direct cell alignment along a guiding axis, which is useful for engineering highly oriented tissues such as muscles and nerves. By using light-responsive LC, researchers can control the topography and surface mechanics spatiotemporal at the micro-scale, allowing for the regulation of cell migration patterns. This helps replicate key features of the original extracellular matrix environment.

The chemical stability, thermal resistance and adaptable mechanical properties of LC polymers make them useful substrate materials for implantable biomedical devices. LC has been micro-fabricated as a substrate for flexible and lightweight microelectrode arrays capable of high-fidelity recording of nerve signals. LC polymers are also promising for the packaging of retinal and cochlear visual/auditory implants because their moisture resistance exceeds that of conventional polymers. However, optical transparency improvements need to be made to improve device performance.

LC biosensors provide a label-free approach for detecting target biomolecules via optical signals generated when analyte binding changes the orientation of the LC matrix. The LC-dense interface on patterned substrates has enabled the highly sensitive detection of nucleic acids and proteins down to the picomolar level by observing changes in birefringent appearance. Similarly, a recognition element-enabled LC-air interface has been designed to detect disease biomarkers and bacterial contamination based on the reorientation of the LCs at the interface.

Lastly, wearable LC devices offer a versatile platform for visual sensing of a wide range of chemical and physical stimuli. Cholesteric LC films can display reversible and measurable color changes in response to mechanical strain, temperature, humidity and biomarkers by tuning the helix pitch. The research team has developed a customizable patch of LC-based sensors that synchronously monitor human movement and health indicators such as glucose levels in sweat. With further development, wearable LC sensors can provide continuous, non-invasive health monitoring to improve diagnostic and therapeutic interventions.

In short, liquid crystals are an interesting class of functional soft materials that exhibit structural regularity and adaptable fluidity. Interdisciplinary research over the past decades has uncovered their enormous potential for advancing biomedical technologies, from targeted drug delivery systems to high-performance biosensors. While challenges remain in optimizing the biostability and biocompatibility of LCs for prolonged human use, these dynamic materials hold promise for future human health benefits thanks to their characteristic excitability-response and biologically relevant optical and mechanical properties that interact with living systems.

Michael Berger

– Michael is the author of three books by the Royal Society of Chemistry:
Nano-Society: Pushing the Boundaries of Technology,
Nanotechnology: A Small Future And
Nanoengineering: Skills and Tools for Making Technology Invisible
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