Image-guided Mechatronic Delivery of Retinal Stem Cells: Tool Design and Navigation –System Development
Potentially blinding retinal diseases affect millions of people worldwide. Current treatments include surgery and drug delivery to the posterior retina, with gene therapies and stem-cell delivery showing increasing promise for restoring vision. Age-Related Macular Degeneration (AMD), for example, may be rendered treatable through therapies with stem cells that may restore the functionality of the retinal pigment epithelium (RPE). This is a cell mono-layer located between the photoreceptor and choroidal layer. The RPE is only a few micrometers thick. Precision micromanipulation requirements and lack of engineering solutions limit the potential impact of RPE sheet transplantation at present.
The objective of this project is to address this lack of instrumentation and enhance the precision and success of subretinal stem-cell derived RPE delivery using optical coherence tomography (OCT)-based image-guidance and novel force-sensing microsurgical instruments. The project revolves around three complementary pillars:
- Design and development of an ungrounded hand-held mechatronics tool that can deliver a rolled millimetre-long stem cell sheet with force-scaling and motion-scaling capabilities. To develop the delivery tool, technologies inspired from piezoelectrics, electro-active polymers, or concentric tubes will be explored. Additionally, new strategies inspired by recent reports on injectable electronics will also be considered for a novel and flexible delivery mechanism.
- Design and development of a force-sensitive sleeve by integrating high-resolution 3D-printed pressure sensors on PDMS films. The force-sensitive sleeve will be integrated on the delivery tool to report tool-tissue interaction forces and therapeutic-delivery volumes at the microscale.
- To devise ways to exploit the continuous force signals from delivery tool to enhance the real time clinical ophthalmoscopic field of view.
The state-of-the-art in retinal ophthalmic surgery involves using micrometre-diameter tools to perform delicate diabetic and scar related delaminations or energy delivery to leaky vessels on the surface of the retina. Delivery of novel therapeutics, such as stem cells or genes, requires access to specific subretinal locations with precision on the order of micrometers. Such precision is at the limits of human capabilities, and, hence, these interventions would benefit both from mechatronics and image-guidance. A co-manipulated robotic system operating under OCT guidance would facilitate the delivery of therapeutics exactly at the desired locations. Further, with force and pressure sensing capabilities, this system would be able to help regulate tool/tissue interaction to safe levels, and help control the volume of therapeutics delivered.
The proposed integrated system – with clear emphasis on ophthalmological surgical tools – will find extensive applications in treatment of diseases such as Age-Related Macular Degeneration, which affect several millions of people worldwide. The project is a clear fit to the CDT clinical research theme of Ophthalmology.