Biomaterials Enhanced Regeneration of the Human Cornea: From Bench to Bedside
Our overall objective is to develop new biomimetic materials that support the regeneration of diseased or damaged corneas as an alternative to the use of human donor allograft corneas, which are in short supply in many countries, for transplantation. We have developed a range of biointeractive materials and one of these iterations was inplanted into 10 patients in a Phase I clinical study. At 24 months post-operative, six of the ten patients could see four times further than before the operation. With the help of rigid contact lenses – the results in all ten patients were similar to what the traditional corneal transplant with human donor tissue would be, with one patient achieving 20/20 vision and two others with 20/25 vision. At 4 years post-operative, the implants continue to be stable. Significantly, there were fewer inflammatory cells in biosynthetic implants observed than in donor allografts.
However, these EDC-crosslinked corneas were not suitable in alkali-burnt corneas, unlike collagen-MPC corneas that appeared to block neovascularuzation. While able to withstand neovascularization, they were also able to support the regeneration of the different nerve sub-types in the cornea. In addition, they could be modified to release drugs for high risk transplantation. We have EU ERA-net nanomedicine funding for this project, I-CARE.
- Hackett, J.M., Lagali, N., Merrett, K., Edelhauser, E., Sun, Y., Gan, L, Griffith, M.,* and Fagerholm, P.* (2011) Biosynthetic corneal implants for replacement of pathologic corneal tissue: performance in a controlled rabbit alkali burn model. Invest. Ophthalmol. Vis. Sci. 52: 651-657 (* denotes equal contribution).
- Fagerholm, P., Lagali, N.S., Merrett, K., Jackson, W.B., Munger, R., Liu, Y., Polarek, J.W., Söderqvist, M. and Griffith, M. (2010) A biosynthetic alternative to human donor tissue for inducing corneal regeneration: performance in a controlled rabbit alkali burn model. Sci Transl Med. 2(46):46ra61.
- Bareiss, B., Ghorbani, M., Li, F., Blake, J.A., Scaiano, J.C., Zhang, J., Deng, C., Merrett, K.,Harden, J., Diaz-Mitoma, F. and Griffith, M. (2010) Controlled release of acyclovir through bioengineered corneal implants with silica nanoparticle carriers. Open Tissue Eng Regen Med J. 3: 10-17.
- McLaughlin, C.R., Acosta, C.M., Luna, C., Liu, W., Belmonte, C, Griffith, M*., and Gallar, J* (2010) Regeneration of Functional Nerves within Full Thickness Collagen-Phosphorylcholine Corneal Substitute Implants in Guinea Pigs. Biomaterials 31: 2770-2778. (* denotes equal contributions; Griffith-corresponding author).
- Liu, W., Deng, C., McLaughlin, C.R., Fagerholm, P., Watsky, M.A., Heyne, B., Scaiano, J.C., Lagali, N.S., Munger, R., Li, F. and Griffith, M. (2009) Collagen-phosphorylcholine interpenetrating network hydrogels as corneal substitutes. Biomaterials 30: 1551-1559.
- Dravida, S., Gaddipati, S., Griffith, M., Merrett, K., Lakshmi, S., Sangwan, V.S., Vemuganti, G.K. (2008) A biomimetic scaffold for culturing limbal stem cells: Promising alternative for clinical transplantation. J. Tissue Eng. Regen. Med. 2: 263-271.
- Merrett, K., Fagerholm, P., McLaughlin, C.R., Dravida, S., Lagali, N., Shinozaki, N., Watsky, M.A., Munger, R., Kato, Y., Li, F., Marmo, C.J. and Griffith, M. (2008) Tissue engineered recombinant human collagen-based corneal substitutes for implantation: performance of type I versus type III collagen. Invest. Ophthalmol. Vis. Sci. 49: 3887-3894.
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