Matrimeres are systemic nanoscale mediators of tissue integrity and function

Area of Science:

• Biomaterials Science
• Cell Biology
• Regenerative Medicine

Background:

• Restoring tissue barriers after injury is vital for regeneration, but mechanisms remain unclear, especially with compromised extracellular matrix.
• The role of nanoscale mediators in maintaining tissue integrity and function during repair processes is not well understood.

Approach:

• Discovered matrimeres: non-vesicular nanoparticles composed of matrix proteins (e.g., fibronectin) and DNA scaffolds, secreted by cells.
• Reconstituted matrimeres *in vitro* using purified fibronectin, vitronectin, and DNA under acidic conditions, mimicking cellular assembly.
• Investigated the *in vivo* behavior of plasma fibronectin matrimeres, noting a significant decrease during systemic inflammatory injury.

Key Points:

• Matrimeres are assembled by mesenchymal stromal cells from fibronectin and DNA within acidic intracellular compartments.
• Synthesized cell-free matrimeres using purified matrix proteins and DNA, guided by specific molecular interactions.
• Plasma fibronectin matrimere levels decrease during inflammatory injury, suggesting a role in disease pathology.

Conclusions:

• Exogenously administered matrimeres rapidly restore vascular integrity by promoting endothelial cell reannealing post-injury.
• Synthesized matrimeres are persistent in host tissue matrix, indicating potential for sustained therapeutic effects.
• Scalable production of matrimeres presents a promising, biologically inspired platform for regenerative nanomedicine applications.