Stable corneal regeneration four years after implantation of a cell-free recombinant human collagen scaffold

Abstract

We developed cell-free implants, comprising carbodiimide crosslinked recombinant human collagen (RHC), to enable corneal regeneration by endogenous cell recruitment, to address the worldwide shortage of donor corneas. Patients were grafted with RHC implants. Over four years, the regenerated neo-corneas were stably integrated without rejection, without the long immunosuppression regime needed by donor cornea patients. There was no recruitment of inflammatory dendritic cells into the implant area, whereas, even with immunosuppression, donor cornea recipients showed dendritic cell migration into the central cornea and a rejection episode was observed. Regeneration as evidenced by continued nerve and stromal cell repopulation occurred over the four years to approximate the micro-architecture of healthy corneas. Histopathology of a regenerated, clear cornea from a regrafted patient showed normal corneal architecture. Donor human cornea grafted eyes had abnormally tortuous nerves and stromal cell death was found. Implanted patients had a 4-year average corrected visual acuity of 20/54 and gained more than 5 Snellen lines of vision on an eye chart. The visual acuity can be improved with more robust materials for better shape retention. Nevertheless, these RHC implants can achieve stable regeneration and therefore, represent a potentially safe alternative to donor organ transplantation.

Nano-Engineered Biomaterials for Tissue Regeneration: What Has Been Achieved So Far?

“…Visual acuity among patients was similar to normal cornea function across the study (Fagerholm et al, 2010). Furthermore, sufficient nerve regeneration and stromal repopulation was found in patients over a 4-year period following the original study (Fagerholm et al, 2014). The long-term safety and efficacy denoted in these studies is promising for future applications.…”

Biomaterials for Regenerative Medicine Approaches for the Anterior Segment of the Eye

“…In a 4 year follow up of ten patients using this technique for partial thickness grafts it is reported that these implants have integrated and are stable (Figure 6). [42] More recently, a modification to these scaffolds has incorporated synthetic phospholipids to inhibit neovascularization for application in more complex corneal disorders. [43] Collagen type 1 (equine) has also been crosslinked using riboflavin and ultraviolet A (UVA), similar to the clinical treatment for keratoconus, and this has been shown to reduce the degradation of the collagen in vitro and after implantation intrastromally in rabbits.…”

“…Reproduced with permission. [42] Copyright 2014, Elsevier. cells in culture on a substrate so that one donor cornea could be used to treat more than one patient.…”

Corneal Tissue Engineering: Recent Advances and Future Perspectives

“…86 A 4-year follow-up showed the construct stably integrated without rejection, whereas future steps are focused on improving visual acuity based on materials with better shape retention. 87 …”