A hyaluronic acid derivative as a coating film for an electrospun cell releasing system in the treatment of corneal wounds

Abstract

The transparency of the cornea is maintained by the stem cells of the corneal epithelium in the limbal region; damage to the limbus may cause partial or total limbal stem cell deficiency that, may lead to blindness. The transplantation of cells is crucial to regenerate the damaged areas. The techniques currently employed consist in cadaveric corneal transplantation or in the use of amniotic membrane as a carrier for delivering cultured limbal stem cells to the cornea. Both these approaches show severe drawbacks such as the potential reject of the transplanted cornea and the risk of viral disease transmissions. Here we report the production of an electrospun device that could be exploited as a scaffold for the culture of corneal epithelial/stem cells and for their subsequent release onto the corneal surface. Such device is composed by a micro fibrillar electrospun mat covered by a polymeric film able, in vitro, to allow the attachment of the cells and to promote potentiallly, when implanted in vivo, their release onto the cornea as a result of a non invasive treatment. Polylactic acid was employed as starting material to obtain the structural basis of the device because of its peculiar mechanical properties that could facilitate its safe implantation onto the cornea. The coating was conducted by soaking the electrospun mat in a solution of a derivative of hyaluronic acid (named HA-EDA-C18) employed as film-forming reversible coating system. We demonstrated that HA-EDA-C18 film can be rapidly dissolved by treating it with a solution containing hydroxypropyl beta-cyclodextrin (HP-beta-cyd). Fibronectin was physically adsorbed onto the HA-EDA-C18 film to facilitate the in vitro attachment of corneal epithelial cells. In vitro studies reveal that, the device is able to release viable cells already 24 h after the treatment with HP-beta-cyd solution as a result of the coating film dissolution.