Elucidating Mechanisms of Gelation, Fiber Assembly, and Stability of Injectable Decellularized Extracellular Matrix...

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Biochemistry

Background:

• Decellularized extracellular matrix (dECM)-based biomaterials are crucial for tissue engineering.
• Pepsin digestion yields injectable forms like ECM hydrogels and intravascularly infusible ECM (iECM).
• Limited characterization hinders understanding of gelation mechanisms and fibril assembly in these materials.

Purpose of the Study:

• To elucidate the fundamental mechanisms driving ECM hydrogel gelation and iECM nanofibril assembly.
• To determine optimal storage conditions for rehydrated dECM formulations to ensure stability.
• To investigate the role of type I collagen in the self-assembly of injectable dECM biomaterials.

Main Methods:

• Second-harmonic generation microscopy to visualize fibril formation and self-assembly.
• Transmission electron microscopy to analyze nanofibril morphology and assembly.
• Bulk material characterization techniques to assess material properties post-rehydration.

Main Results:

• Type I collagen's lateral and longitudinal growth was identified as the primary driver of ECM hydrogel formation.
• Intravascularly infusible ECM (iECM) demonstrated nanofiber assembly without gelation, preserving original mechanisms.
• Decellularized extracellular matrix formulations are best stored at 4°C for up to 24 hours after rehydration to maintain properties.

Conclusions:

• Type I collagen directs the self-assembly of heterogeneous, injectable, decellularized ECM biomaterials.
• Understanding self-assembly mechanisms is key to developing advanced tissue engineering scaffolds.
• Clinically relevant storage conditions (4°C, 24h) are established for maintaining the integrity of injectable dECM biomaterials.