Tissue-derived microparticles reduce inflammation and fibrosis in cornea wounds

Biological materials derived from the extracellular matrix (ECM) of tissues serve as scaffolds for rebuilding tissues and for improved wound healing. Cornea trauma represents a wound healing challenge as the default repair pathway can result in fibrosis and scar formation that limit vision. Effective treatments are needed to reduce inflammation, promote tissue repair, and retain the tissue's native transparency and vision capacity. Tissue microparticles derived from cornea, cartilage and lymph nodes were processed and screened in vitro for their ability to reduce inflammation in ocular surface cells isolated from the cornea stroma, conjunctiva, and lacrimal gland. Addition of ECM particles to the media reduced expression of inflammatory genes and restored certain tear film protein production in vitro. Particles derived from lymph nodes were then applied to a rabbit lamellar keratectomy corneal injury model. Application of the tissue particles in a fibrin glue carrier decreased expression of inflammatory and fibrotic genes and scar formation as measured through imaging, histology and immunohistochemistry. In sum, immunomodulatory tissue microparticles may provide a new therapeutic tool for reducing inflammation in the cornea and ocular surface and promoting tissue repair. STATEMENT OF SIGNIFICANCE: Damaged cornea will result in scar tissue formation that impedes vision, and new therapies are needed to enhance wound healing in the cornea and to prevent fibrosis. We evaluated the effects of biological scaffolds derived extracellular matrix (ECM) during corneal wound healing. These ECM particles reduced inflammatory gene expression and restored tear film production in vitro, and reduced scar formation and fibrosis genes in the wounded cornea, when applied to in vivo lamellar keratectomy injury model. The immunomodulatory tissue microparticles may provide a new therapeutic tool for reducing inflammation in the cornea and ocular surface and promoting proper tissue repair.