Controlling hydrogel’s properties with photocrosslinking
During the month of September, we showed some applications involving photostimulation of hydrogels. The use of light to induce reactions in materials is closer to our daily life than we think. A popular one is in the treatment of dental cavities or reparative procedures in which dentists apply a strong light to finalize the curing of resins. Some types of paintings and protective coatings also require ultraviolet (UV) light to increase the adhesion and gain efficiency in the process. Even in beauty salons, lamp nail lights can be applied to cure some types of nail polishes making them more resistant.
In the biomedical research context, biomaterials based on water and specially natural components (hydrogels) have been investigated with great success for improving or developing novel treatments in healthcare. Since the major constituent of hydrogels is water, their processability can be challenging and their final sturdiness delicate to control. In this light, natural components found in animal tissues and organs such as collagen, gelatin, hyaluronic acid and dextran have been extracted and chemically modified to be able to react under light exposure. In addition to this chemical modification where methacrylate or acrylate groups are added into the polymer chain, a photoinitiator is also needed to generate free radicals and start the reactions. These induced reactions make a liquid solution turn into a solid gel (gelation process).
The use of light for inducing these reactions allows the researcher to have a better control over the processability and the final viscoelastic properties of the hydrogel. In the biomedical context, the first relates to our ability to handle liquid-to-solid phase transitions (in vivo injection, 3D bioprinting, 3D cell culture, etc.). The second relates to the need of controlling the viscoelastic properties of the hydrogel that needs to match the mechanical behavior of the intended implantation site.
Photocrosslinking allows a better control over the hydrogel’s processability
Photocrosslinkable hydrogels have been widely used with 3D printing technologies. The activation of light leads to the gelation of the viscous filament that has been extruded within a few minutes allowing the maintenance of its shape. Another example is injectable hydrogels that have been investigated for filling a damaged area of the body. The viscous solution is inserted with a syringe and the light is applied to make it jellify and stay in place. The image below illustrates the application of injectable hydrogel into bone defects.
The use of light offers better control on the initiation and speed of the gelation process (temporal control), and also on the location of gelation (spatial control) when compared with hydrogels that jellify under conventional mechanisms (such as temperature, pH, chemicals). In addition, the photocrosslinking can take place at room temperature or under physiological conditions which is very valuable for in vivo applications.
Photocrosslinking allows a better control over the hydrogel’s viscoelastic properties
There are a number of parameters on the formulation and preparation of a photocrosslinkable hydrogel that can be adjusted and combined to tune its gelation kinetics and final viscoelasticity. Among these parameters, we can list the followings:
The concentration of the main protein (e.g. collagen, gelatin) or polysaccharide (e.g. hyaluronic acid, dextran) is one straightforward parameter to vary to change the final properties of the hydrogel. Higher concentrations mean higher amounts of the polymer compared to water and therefore, higher mechanical properties. Another parameter related to the biomaterial itself is their degree of modification. The manufacturer has a relative control over the amount of photosensitive groups (e.g. methacryloyl groups) that they insert into the natural compounds. Higher levels of this functional group will lead to higher crosslinking density, resulting in stiffer hydrogels .
Photoinitiators are light-sensitive compounds that generate free radicals upon exposure to light which will in turn initiate the crosslinking reaction and finally form crosslinked hydrogel networks. The main differences among the photoinitiators investigated in literature relies on their absorption spectrum of light and radical generation mechanism. In any case, the increase of its concentration will result in more free radicals available for the crosslinking, which can accelerate the reaction and potentially achieve higher mechanical properties upon a specific light intensity and exposure time .
C) Light intensity
The light intensity has a great impact on the onset time (time in which the storage modulus increases above a certain baseline value, or time in which tan(𝛿) decreases below a value of 1) and the rate of crosslinking. Depending on the exposure time, it can also affect the final viscoelastic properties of the hydrogel. A higher light intensity will introduce more energy into the sample generating more free radicals for the crosslinking reaction .
D) Light exposure time
A sample exposed longer to light will contain more free radicals and more crosslinking reactions will take place. In this way, its viscoelastic properties will be higher. Contrary to the light intensity, the onset time and the rate of crosslinking should not be affected by the light duration.
In sum, photocrosslinking technology opens new possibilities in the fields of biomedical research and therapies. By both facilitating the spatiotemporal processability and allowing the precise tuning of their viscoelastic properties, photocrosslinkable hydrogels have the potential to improve biomedical treatments and products making them more accessible to the healthcare system. To help in this goal, new testing tools are needed to study and optimize these hydrogels.
 Pepelanova, I., Kruppa, K., Scheper, T., & Lavrentieva, A. (2018). Gelatin-methacryloyl (GelMA) hydrogels with defined degree of functionalization as a versatile toolkit for 3D cell culture and extrusion bioprinting. Bioengineering, 5(3), 55.
 O’Connell, C. D., Zhang, B., Onofrillo, C., Duchi, S., Blanchard, R., Quigley, A., … & Wallace, G. G. (2018). Tailoring the mechanical properties of gelatin methacryloyl hydrogels through manipulation of the photocrosslinking conditions. Soft matter, 14(11), 2142-2151.