The Intersecting Physical Mechanisms That Regulate Cell Viability in 3D Synthetic Hydrogels

Area of Science:

• Biomaterials Science
• Cell Biology
• Tissue Engineering

Background:

• Hydrogels are widely used in 3D cell culture, but their varying protein transport properties can impact cell viability.
• Synthetic polymer networks often exhibit lower protein permeability than biopolymer networks, potentially affecting encapsulated cells.

Purpose of the Study:

• To investigate whether reduced protein transport in synthetic hydrogels contributes to decreased cell viability.
• To compare cell viability in poly(ethylene glycol) vinyl sulfone (PEG-VS) hydrogels versus Matrigel.
• To quantify the effects of modulus, transport, and confinement on encapsulated cells within different hydrogel environments.

Main Methods:

• Utilized 2D and 3D hydrogel cultures using PEG-VS and Matrigel.
• Employed transwell experiments to decouple serum restriction from cell-gel adhesion.
• Quantified cell viability in response to varying hydrogel properties and serum availability.

Main Results:

• Significantly reduced cell viability was observed in PEG-VS hydrogels compared to Matrigel.
• Serum restriction in transwell experiments mimicked the reduced cell viability seen in 3D cultures.
• Hydrogel-restricted protein transport was identified as a key factor influencing cell viability.

Conclusions:

• Biomaterial-designed protein transport is a critical factor for synthetic 3D cell culture systems.
• Reduced protein and nutrient diffusion in synthetic hydrogels negatively impacts cell viability.
• This study provides a framework for understanding microenvironmental influences on cell viability in engineered tissues.