4.8 Article

Novel Corneal Endothelial Cell Carrier Couples a Biodegradable Polymer and a Mesenchymal Stem Cell-Derived Extracellular Matrix

Journal

ACS APPLIED MATERIALS & INTERFACES
Volume 14, Issue 10, Pages 12116-12129

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsami.2c01709

Keywords

cornea; corneal endothelial cell (CEC); decellularized extracellular matrix; poly(lactide-co-caprolactone) (PLCL); CEC carrier

Funding

  1. Ministry of Trade, Industry & Energy (MOTIE), Republic of Korea [20003915]
  2. National Research Foundation of Korea (NRF) from the Ministry of Science and ICT, Republic of Korea [2020R1A2C2007972]
  3. Korea Evaluation Institute of Industrial Technology (KEIT) [20003915] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
  4. National Research Foundation of Korea [2020R1A2C2007972] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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In this study, a transparent, biodegradable, and cell-adhesive carrier for corneal endothelial cell transplantation was developed. The carrier showed good cell attachment and cell viability and was able to maintain normal cornea properties. The results suggest that this carrier holds promise as an ideal option for corneal endothelial cell transplantation.
Here, we report a transparent, biodegradable, and cell-adhesive carrier that is securely coupled with the extracellular matrix (ECM) for corneal endothelial cell (CEC) transplantation. To fabricate a CEC carrier, poly(lactide-co-caprolactone) (PLCL) solution was poured onto the decellularized ECM (UMDM) derived from in vitro cultured umbilical cord blood-MSCs. Once completely dried, ECM-PLCL was then peeled off from the substrate. It was 20 mu m thick, transparent, rich in fibronectin and collagen type IV, and easy to handle. Surface characterizations exhibited that ECM-PLCL was very rough (54.0 +/- 4.50 nm) and uniformly covered in high density by ECM and retained a positive surface charge (65.2 +/- 57.8 mV), as assessed via atomic force microscopy. Human CECs (B4G12) on the ECM-PLCL showed good cell attachment, with a cell density similar to the normal cornea. They could also maintain a cell phenotype, with nicely formed cell-cell junctions as assessed via ZO-1 and N-cadherin at 14 days. This was in sharp contrast to the CEC behaviors on the FNC-coated PLCL (positive control). A function-related marker, Na+/K+-ATPase, was also identified via western blot and immunofluorescence. In addition, primary rabbit CECs showed a normal shape and they could express structural and functional proteins on the ECM-PLCL. A simulation test confirmed that CECs loaded on the ECM-PLCL were successfully engrafted into the decellularized porcine corneal tissue, with a high engraftment level and cell viability. Moreover, ECM-PLCL transplantation into the anterior chamber of the rabbit eye for 8 weeks proved the maintenance of normal cornea properties. Taken together, this study demonstrates that our ECM-PLCL can be a promising cornea endothelium graft with an excellent ECM microenvironment for CECs.

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