Biocompatible Scaffolding: Aiming for the Moon

In a survey of more than 100 cornea specialists, 55% had no preference regarding the source of cells required for endothelial therapy. Could biocompatible scaffolds gain traction as a result?

“When we look at the scaffold approaches, it’s the interaction between the cells and the underlying Descemet’s membrane that gives us inspiration. We want to recreate this in the lab,” said Sorcha Ní Dhubhghaill MD, PhD.

“What we want is an endothelial cell that attaches nicely and firmly to our scaffold. We want the scaffolds because they are a targeted therapy, can be affixed to the site, and may perhaps reduce cell spread.”

Professor Ní Dhubhghaill strongly believes this therapy has considerable potential. Based on a 3D structure made of natural or synthetic materials, biocompatible scaffolds can mimic the extracellular matrix (ECM) of native eye tissue.

Amniotic membrane and lens capsules can be used to create biocompatible scaffolds, but there are more options when it comes to synthetics. Prof Ní Dhubhghaill said that natural polymers like collagen can be used, as can a host of semi- and fully synthetic materials, such as polycaprolactone.

The natural model for biocompatible scaffold design is the Descemet’s membrane, and the goal is to be able to recreate its key properties, Prof Ní Dhubhghaill said. Endothelial cells—either from donor tissue, cultured primary cells, or induced pluripotent stem cells (iPSCs)—are seeded onto the scaffold in vitro as part of this process, but it does pose a challenge.

“We’re calling this the moonshot project because that is what this approach is. It’s a moonshot; it’s quite an ambitious way to go,” Prof Ní Dhubhghaill said.

“I have used scaffolds that have been beautifully cellularised, and at the last moment, when we were introducing them into a surgical model, the cells fell off. That is absolutely not what we want to do when developing a scaffold.”

Other difficulties reported by Prof Ní Dhubhghaill included problems with mimicking the Descemet’s membrane, material limitations that could cause the scaffolds to become rigid or slippery, and regulatory and cost barriers. All of these would need to be addressed before widespread adoption.

However, thanks to the familiarity of a surgical graft approach for biocompatible scaffolds, along with their consistency and scalability (potentially based on a ‘cookie-cutter’ approach), Prof Ní Dhubhghaill’s moonshot may not be so far out of reach. It is an ambitious target, but one she feels can be achieved.

“It’s not clear yet whether scaffolds are the future. In a world where we can get what we want with iPSCs, I think they could really take off,” Prof Ní Dhubhghaill said.

“Biocompatible scaffolds could also limit spread of cells in the anterior chamber, which I think would be of particular interest. However, they may also require more complex regulation than pure cells, and that will translate into an addition in price.”

Prof Ní Dhubhghaill presented at the 2025 ESCRS Annual Congress in Copenhagen.

Sorcha Ní Dhubhghaill MBBCh, BaO, PhD, Dip(stats), FEBO, FEBOS-CR, MRCSI(Ophth) is Head of Department, Ophthalmology at Brussels University Hospital, Belgium. sorcha.ni.dhubhghaill@uzbrussel.be