Targeted micro-heterogeneity in bioinks allows for 3D printing of complex constructs with improved resolution and...

Area of Science:

• Biomaterials Science
• Biotechnology
• Tissue Engineering

Background:

• Three-dimensional (3D) bioprinting offers versatile biomedical applications.
• Ideal bioinks require a complex micro-environment, good printability, and high cell viability.
• Gelatin-based bioinks are widely used but can be improved for advanced applications.

Purpose of the Study:

• To develop strategies for enhancing gelatin-based bioinks heterogeneity on a 1-100 µm length scale.
• To improve printing quality and cell viability in 3D bioprinted constructs.
• To characterize the impact of micro-heterogeneities on bioink mechanical properties and printability.

Main Methods:

• Utilized multiple particle tracking microrheology for spatial and micro-mechanical characterization of hydrogel heterogeneity.
• Introduced micro-heterogeneities by adding poly(vinyl alcohol) to gelatin gels, inducing micro-phase separation.
• Created gelatin/nanoclay composites to investigate alternative methods for enhancing bioink properties.

Main Results:

• Poly(vinyl alcohol) addition formed viscous inclusions in gelatin, leading to enhanced slip and superior printing quality.
• Both poly(vinyl alcohol) and nanoclay strategies resulted in high viability for human hepatocellular carcinoma (HepG2) and normal human dermal fibroblast (NHDF) cells.
• Gelatin/nanoclay composites showed reduced critical stress of gel fracture, facilitating extrusion and improving printability.

Conclusions:

• Targeted introduction of micro-heterogeneities via micro-phase separation is effective for high-resolution 3D bioprinting.
• Achieving good printing quality requires heterogeneities substantially smaller than the desired feature size.
• These enhanced bioinks show promise for fabricating complex 3D tissue constructs with high cell viability.