Deciphering the Molecular Mechanism of Water Interaction with Gelatin Methacryloyl Hydrogels: Role of Ionic Strength, pH, Drug Loading and Hydrogel Network Characteristics

Abstract

Water plays a primary role in the functionality of biomedical polymers such as hydrogels. The state of water, defined as bound, intermediate, or free, and its molecular organization within hydrogels is an important factor governing biocompatibility and hemocompatibility. Here, we present a systematic study of water states in gelatin methacryloyl (GelMA) hydrogels designed for drug delivery and tissue engineering applications. We demonstrate that increasing ionic strength of the swelling media correlated with the proportion of non-freezable bound water. We attribute this to the capability of ions to create ion–dipole bonds with both the polymer and water, thereby reinforcing the first layer of polymer hydration. Both pH and ionic strength impacted the mesh size, having potential implications for drug delivery applications. The mechanical properties of GelMA hydrogels were largely unaffected by variations in ionic strength or pH. Loading of cefazolin, a small polar antibiotic molecule, led to a dose-dependent increase of non-freezable bound water, attributed to the drug’s capacity to form hydrogen bonds with water, which helped recruit water molecules in the hydrogels’ first hydration layer. This work enables a deeper understanding of water states and molecular arrangement at the hydrogel–polymer interface and how environmental cues influence them.

Sustained released of bioactive mesenchymal stromal cell‐derived extracellular vesicles from 3D‐printed gelatin methacrylate hydrogels

“…35 Other studies have demonstrated that GelMA formulation parameters such as ionic strength and pH can affect cargo loading, GelMA mesh characteristics, and overall net charge. 36 Although EV/GelMA electrostatic interactions were beyond the scope of this study, EVs generally carry a net negative charge and such interactions may be an important factor to consider in future studies.…”

Semi-Synthetic Click-Gelatin Hydrogels as Tunable Platforms for 3D Cancer Cell Culture

“…Additionally, MCF-7 spheroid formation was observed by day 14 of culture (Figure 7E). This was expected based on the Young's moduli of the Gel-SH/PEG-4MAL hydrogels (Figures 4 and 5), where hydrogels possessed Young's moduli similar to that of breast fat and fibroglandular tissue (roughly 2.5-3.5 kPa) [82][83][84][85]. From the conditions tested, it was observed that 5% (w/v) Gel-SH hydrogels provided the most suitable environment for spheroid formation, as spheroids appeared more frequently and greater in size in these hydrogels compared to 10% (w/v) and 2.5% (w/v) Gel-SH hydrogels.…”

“…Regarding the culture of breast cancer cells, through compression testing, Samani et al found that breast fat and fibroglandular tissues exhibited Young’s moduli of 3.25 kPa, whereas breast cancer tumors possessed Young’s moduli ranging from 6.41 kPa to 42.51 kPa, depending on the type of tumor [ 82 ]. Using alternative methods of measurement, other studies have found that breast fibroglandular tissues typically possess Young’s moduli between 2.5 kPa and 3.5 kPa [ 83 , 84 , 85 ]. Therefore, Gel-SH/PEG-4MAL hydrogels would be suited for the culture of breast cancer cells, as the Young’s moduli of breast fat and fibroglandular tissues is similar to that of Gel-SH/PEG-4MAL hydrogels.…”

Cation release from different carboxymethyl cellulose hydrogels

“…In contrast, DG-7 exhibits the lowest electrostatic repulsion between the polymer chains and therefore the tightest structure. The addition of divalent Fe ions increases the ionic strength [63,64] of the external solution resulting in a lower mesh size for Fe-7 and Fe-9 compared to DG-7 and DG-9. As an exception to the expected trend, Fe-12 shows a small increase in mesh size compared to DG-12, indicating another unknown interaction that may play a role here.…”