Rethinking Matrigel: The Complex Journey to Matrix Alternatives in Organoid Culture

Area of Science:

• Cell Biology
• Biomaterials Science
• Tissue Engineering

Background:

• Matrigel provides a basement membrane-like scaffold crucial for 3D cell cultures and organoid research.
• Its undefined, variable, and murine origin presents ethical and scientific challenges, hindering human model translation.
• Despite limitations, Matrigel is widely used in human 3D culture systems.

Purpose of the Study:

• To explore the reasons behind Matrigel's continued use in human 3D culture systems.
• To identify challenges hindering the transition to alternative, xeno-free matrices.
• To propose strategies for developing and selecting suitable matrix alternatives.

Main Methods:

• Literature review and critical analysis of Matrigel's properties and limitations.
• Exploration of current challenges in adopting alternative matrices.
• Development of recommendations for matrix selection and evaluation.

Main Results:

• Matrigel's complex composition and biomimicry contribute to its widespread adoption.
• Significant challenges exist in transitioning to xeno-free alternatives due to performance and standardization issues.
• A one-for-all approach is insufficient; tissue- and model-specific matrix design is necessary.

Conclusions:

• Researchers face hurdles in moving away from Matrigel due to its established performance and lack of suitable alternatives.
• Developing and implementing xeno-free human model systems requires a shift towards tailored matrix solutions.
• A matrix selection checklist, scaffold assessment tool, and quantitative criteria are proposed to aid in adopting alternatives.