Tissue Architecture Modulates Compositional and Structural Properties of Corneal Myofibroblast-Derived Matrix

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Ophthalmology Research

Background:

• Corneal scarring significantly impacts vision, necessitating better understanding of healing mechanisms.
• Current in vitro models often fail to replicate the complex in vivo corneal microenvironment.
• Identifying key regulators of extracellular matrix deposition is vital for preventing pathological scarring.

Purpose of the Study:

• To create a novel 3D in vitro model simulating human corneal healing.
• To investigate the role of microenvironmental alignment in corneal myofibroblast behavior and extracellular matrix production.
• To uncover mechanisms underlying corneal healing and scarring processes.

Main Methods:

• Cultured corneal myofibroblasts in fibrin hydrogels with aligned (healthy) and random (wounded) configurations.
• Utilized TGF-β1 induction to mimic fibrotic responses.
• Assessed cellular (α-SMA) and matrix (collagen, fibronectin, decorin, tenascin C) components and structural properties.

Main Results:

• Aligned constructs showed increased synthesis of total soluble proteins and collagen type V, but reduced collagen type I.
• Larger collagen fibril diameters were observed in aligned compared to random constructs.
• Differential expression of fibronectin, decorin, and tenascin C was noted between aligned and random groups.

Conclusions:

• Microenvironmental alignment critically modulates extracellular matrix structural properties during corneal healing.
• Alignment influences the synthesis of key proteins involved in fibrillogenesis and ECM quality.
• The developed 3D model provides a platform for studying corneal regeneration and developing anti-scarring therapies.