Modulation of Methacrylated Hyaluronic Acid Hydrogels Enables Their Use as 3D Cultured Model

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Cell Biology

Background:

• Bioengineered hydrogels offer physiologically relevant platforms for studying cell behavior in tissue engineering, regenerative medicine, and in vitro disease models.
• Hyaluronic acid (HA) is a biocompatible natural polymer and a major extracellular matrix (ECM) component, ideal for investigating cellular crosstalk, adhesion, and proliferation.
• Chemically modified HA with photo-crosslinkable methacrylated groups (HA-MA) can be synthesized into hydrogels with tunable properties.

Purpose of the Study:

• To synthesize and characterize HA-MA hydrogels with controlled bulk properties for biocompatible scaffold development.
• To evaluate the morphological evolution and proliferation rates of glioblastoma cells (U251-MG) cultured on HA-MA surfaces in 2D versus 3D environments.
• To assess the impact of hydrogel dimensionality on glioblastoma cell functions, interactions, survival, and invasiveness.

Main Methods:

• Synthesis of HA-MA hydrogels under controlled pH and temperature.
• Characterization using rheological studies, mechanical testing, and scanning electron microscopy (SEM).
• Culturing U251-MG glioblastoma cells on 2D and 3D HA-MA scaffolds, followed by cell viability assays, mitochondrial metabolism evaluation, and morphological studies.

Main Results:

• HA-MA hydrogels exhibited optimal biomechanical and biocompatible properties suitable for scaffold development.
• A change in dimensionality from 2D to 3D significantly impacted glioblastoma cell functions and interactions.
• Cell viability and mitochondrial metabolism assays confirmed that the hydrogels did not impede cell survival.
• Morphological studies revealed cell-matrix interactions that promoted spheroid budding and invasiveness.

Conclusions:

• Chemically modified hyaluronic acid hydrogels provide a tunable and biocompatible scaffold for cell culture.
• The 3D microenvironment significantly influences glioblastoma cell behavior, including proliferation and invasiveness.
• These HA-MA hydrogels represent a valuable tool for in vitro modeling of glioblastoma and for advancing tissue engineering applications.