Microdevice-based cell therapy for age-related macular degeneration

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Ophthalmology

Background:

• Age-related macular degeneration (AMD) is a leading cause of vision loss.
• Current therapies for AMD have limitations, necessitating innovative approaches.
• The Bruch's membrane plays a critical role in retinal health and function.

Purpose of the Study:

• To develop and evaluate a micromachined parylene-C device as an artificial Bruch's membrane for stem cell-based AMD therapy.
• To assess the suitability of parylene-C as a substrate for retinal pigment epithelial (RPE) cell culture and transplantation.
• To demonstrate the feasibility of surgical implantation of the artificial membrane in a preclinical model.

Main Methods:

• Fabrication of submicron parylene-C membranes and mesh-supported submicron parylene membranes (MSPMs).
• Evaluation of membrane permeability, molecular weight exclusion, and nutrient diffusion.
• In vitro culture of human embryonic stem cell-derived RPE cells on MSPMs.
• Surgical implantation of MSPMs with RPE cells into rat retinas using a parylene-C/SU-8 microfluidic inserter.
• Histological and immunofluorescence analysis of implanted tissues.

Main Results:

• Parylene-C membranes <0.3 µm thick mimic healthy Bruch's membrane permeability and nutrient transport.
• MSPMs provide mechanical support and enable monolayer growth of RPE cells with polarized morphology.
• Implanted RPE cells adhered well to the artificial Bruch's membrane in vivo.
• RPE cells maintained high viability and normal morphology post-implantation.

Conclusions:

• Parylene-C is a viable material for creating artificial Bruch's membranes for AMD therapy.
• The MSPM design offers a practical solution for handling and surgical implantation.
• This approach shows promise for restoring RPE function and preserving vision in AMD patients.