Injury-Free In Vivo Delivery and Engraftment into the Cornea Endothelium Using Extracellular Matrix Shrink-Wrapped Cells

Cell injection is a common clinical approach for therapeutic delivery of cells into diseased and damaged tissues in order to achieve regeneration. However, cell retention, viability, and engraftment at the injection site has generally been poor, driving the need for improved approaches. Here, we developed a technique to shrink-wrap micropatterned islands of corneal endothelial cells in a basement membrane-like layer of extracellular matrix (ECM) that enables the cells to maintain their cell-cell junctions and cytoskeletal structure while in suspension. These μMonolayers exhibited the ability to rapidly engraft into intact, high-density corneal endothelial monolayers in both in vitro and in vivo model systems. Importantly, the engrafted μMonolayers increased local cell density, something that the clinical-standard single cells in suspension failed to do. These results show that shrink-wrapping cells in ECM dramatically improves engraftment and provides a potential alternative to cornea transplant when low endothelial cell density is the cause of corneal blindness. One Sentence Summary Shrink-wrapped patches of endothelial cells can rapidly attach and integrate into an intact cornea endothelium when injected into the anterior chamber, increasing cell density.