Biomimetic Hydrogels - Tools for Regenerative Medicine, Oncology, and Understanding Medical Gas Plasma Therapy

Abstract

Biomimetic hydrogels enable biochemical, cell biology, and tissue-like studies in the third dimension. Smart hydrogels are also frequently used in tissue engineering and as drug carriers for intra- or extracutaneous regenerative medicine. They have also been studied in bio-sensor development, 3D cell culture, and organoid growth optimization. Yet, many hydrogel types, adjuvant components, and cross-linking methods have emerged over decades, diversifying and complexifying such studies. Here, an evaluative overview is provided, mapping potential applications to the corresponding hydrogel tuning. Strikingly, hydrogels are ideal for studying locoregional therapy modalities, such as cold medical gas plasma technology. These partially ionized gases produce various reactive oxygen species (ROS) types along with other physico-chemical components such as ions and electric fields, and the spatio-temporal effects of these components delivered to diseased tissues remain largely elusive to date. Hence, this work outlines the promising applications of hydrogels in biomedical research in general and cold plasma science in particular and underlines the great potential of these smart scaffolds for current and future research and therapy.

Keywords: CAP; LTP; NTP; non‐thermal plasma; plasma medicine; reactive oxygen species.

Figure 1

Hydrogel classifications by sources, cross‐linking methods, stimuli sensitivities, structures, and applications. Copyright: the authors.

Figure 2

Hydrogels are used for biomedical applications such as drug carriers, regenerative medicine, 3D cell culture, bio‐sensors, wound dressing, and interconnected usages (arrows). Copyright: the authors.

Figure 3

Hydrogels are used as active plasters that enhance hemostasis and have an anti‐microbial effect, control tissue moisture and exchange with the environment, and favor tissue remodeling. Copyright: the authors.

Figure 4

Stimuli classifications for hydrogel activation are categorized as chemical, physical, and biochemical. Copyright: the authors.

Figure 5

Particle embedding in hydrogels allows “smart” shielding for targeted release by external stimuli 1), offers the prolonged release of particles 2), protects the surroundings from potentially harmful compounds, or prevents the compounds from external degradation 3). Copyright: the authors.

Figure 6

Properties of cold physical plasma: plasma is composed of reactive species and charged particles, exudes heat, and radiates electromagnetic fields, UV, and visible light. Copyright: the authors.

Figure 7

Representative images of operating the kINPen plasma device in air and conductive set‐up. Copyright: the authors.

Figure 8

Preparation of plasma‐altered hydrogels by dissolution of hydrogel compound by plasma‐treated solution 1), plasma‐assisted cross‐linking 2), and plasma treatment of polymerized hydrogel 3). Copyright: the authors.

Figure 9

Drug‐release comparison between liquids and hydrogels. Hydrogels offer a prolonged and more steady release (purple), while liquids display a single spike release (blue). Copyright: the authors.

Figure 10

Principle of reactive species generation in the case of an atmospheric pressure argon plasma jet. Reproduced with permission.^{[ 21 ]} Copyright 2021, Elsevier.

Figure 11

Potential symbiosis between cold physical plasma and hydrogels. Benefits offered by plasma technologies for enhanced hydrogel uses (pink top) along with hydrogel intrinsic properties for synergetic outcomes. Copyright: the authors.