Development of a GMP-conform, biocompatible corneal stroma replacement for ocular surface reconstruction

• Applicants: Dr. Christian Lotz; Dr. Sonja Mertsch; Professor Dr. Stephan Reichl; Professor Dr. Stefan Schrader
• Subject Area: Ophthalmology
• Term: since 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 280173526

Ocular surface disorders are the fourth leading cause of blindness worldwide. The allogeneic corneal transplantation and the use of the amniotic membrane for ocular surface reconstruction are the most frequently used treatment methods to date. However, there is a worldwide discrepancy of 1:70 between the available and required corneal donor material. As a result, around 12.7 million patients are currently waiting for a donor cornea. The small total number of corneal donors, but also the limitations of the quality and the standardizable of the donor material as well as transplant rejection due to immune reactions are some reasons for this shortage of material. The need for clinically usable, alternative tissue substitutes for ocular surface reconstruction is higher than ever and of high clinical relevance. Using human cells to generate an artificial tissue followed by decellularization is a very promising approach. Due to the possibility of obtaining a large number of cells from a small tissue biopsy, there is almost no restriction on tissue availability for this approach. Furthermore, it is also possible to produce autologous tissue substitute by using a small biopsy from the patient and thus prevent a possible rejection reaction. In this follow-up study, the previously successfully established and in vitro tested matrices based on human corneal keratocytes will be tested in a mouse model with regard to their biocompatibility. Furthermore, with regard to the application in patients, the bioreactor system will be further improved in order to enable a standardized, GMP-compliant production of corneal substitute tissue under in vivo like conditions. In addition, the culture conditions will be adapted further in order to achieve an increased thickness through cell sheet stacking and an improved transparency by directed growth of the keratocytes in the cell sheets in a shorter time. In the feasibility study for this application it could already be shown that the generation of these cell sheets is possible and that they have promising properties with regard to the usability as replacement tissue. The anticipated outcome of this project is to generate a patient-specific, transparent and GMP-compliant tissue substitute as an alternative to amniotic membrane and to donor corneal material, which can be used in the treatment of ocular surface diseases.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr.-Ing. Jan Hansmann