Designer Descemet Membranes Containing PDLLA and Functionalized Gelatins as Corneal Endothelial Scaffold

Abstract

Corneal blindness is the fourth leading cause of visual impairment. Of specific interest is blindness due to a dysfunctional corneal endothelium which can only be treated by transplanting healthy tissue from a deceased donor. Unfortunately, corneal supply does not meet the demand with only one donor for every 70 patients. Therefore, there is a huge interest in tissue engineering of grafts consisting of an ultra‐thin scaffold seeded with cultured endothelial cells. The present research describes the fabrication of such artificial Descemet membranes based on the combination of a biodegradable amorphous polyester (poly (d,l‐lactic acid)) and crosslinkable gelatins. Four different crosslinkable gelatin derivatives are compared in terms of processing, membrane quality, and function, as well as biological performance in the presence of corneal endothelial cells. The membranes are fabricated through multi‐step spincoating, including a sacrificial layer to allow for straightforward membrane detachment after production. As a consequence, ultrathin (<1 µm), highly transparent (>90%), semi‐permeable membranes could be obtained with high biological potential. The membranes supported the characteristic morphology and correct phenotype of corneal endothelial cells while exhibiting similar proliferation rates as the positive control. As a consequence, the proposed membranes prove to be a promising synthetic alternative to donor tissue.

Effect of Rho-Associated Kinase Inhibitor and Mesenchymal Stem Cell-Derived Conditioned Medium on Corneal Endothelial Cell Senescence and Proliferation

“…Cells with an underdeveloped tight junction may have low ZO-1 level, and active and proliferative cell cycles (Y-CM). Similar results were observed with corneal endothelial cells cultured on the collagen-vitrigel membrane [24,25].…”

Corneal endothelium tissue engineering: An evolution of signaling molecules, cells, and scaffolds toward 3D bioprinting and cell sheets

“…The final scaffold was ultrathin (<1 µm) and very transparent and had semipermeable membranes and great biological potential. The cultured HCECs on this scaffold had a natural morphology and an acceptable proliferation rate (Van Hoorick et al, 2020).…”

The Advantages of Polymeric Hydrogels in Calcineurin Inhibitor Delivery

“…The combination of these two biomaterials provides the ideal environment for cytocompatibility and cellular interaction exhibited by gelatin. In addition, PDLLA provides appropriate mechanical resistance for the graft tissue in corneal endothelial transplant [21]. v.…”

“…(A) (B) The recent studies on Alg-based hydrogels primarily focused on improving the mechanical properties [58,88], manufacturing methods [89,90], payload of gels [21], and transport and release of hydrophilic and hydrophobic drugs [91,92] such as CNIs. These Alg-based PolyHy are good drug delivery systems for the brain, cancer, antibacterial activity, immunosuppressive therapies, etc.…”