Recent Advances in Biosynthetic Corneal Substitutes
- 41 Downloads
Purpose of Review
Regeneration of the corneal epithelium and endothelium has been achieved, but regeneration of the corneal stroma has not, because it has several remarkable properties, including high tensile strength, thrust resistance, and high transparency. We introduce several biosynthetic approaches to creating stromal substitutes closely resembling the native human corneal stroma are currently being studied.
Currently, there are five approaches to regenerate corneal stroma: (1) decellularization, (2) the use of human recombinant collagen (HRC), (3) optical clarification (and lamination), (4) cell-based regeneration, and (5) organoid generation with induced pluripotent stem (iPS) cells.
Immediate next steps for this area of research include clinical trials of decellularized stromal scaffolds created from porcine corneas or RHC. While these methods have both advantages and disadvantages, their refinement and clinical use, as well as the use of other methods, promise to lead to the continuing development of new approaches.
KeywordsCorneal substitutes Decellularization Human recombinant collagen Optical clarification Cell-based regeneration Organoid generation
Compliance with Ethical Standards
Conflict of Interest
Shunji Yokokura and Yuji Tanaka declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article contains studies with human and animals. These studies followed the tenets of the Declaration of Helsinki and all study protocols were approved by the Institutional Ethics Committees of Tohoku University hospital
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 5.• Zhang MC, Liu X, Jin Y, Jiang DL, Wei XS, Xie HT. Lamellar keratoplasty treatment of fungal corneal ulcers with acellular porcine corneal stroma. Am J Transplant. 2015;15:1068–75. https://doi.org/10.1111/ajt.13096. This study suggests that these acellular scaffolds steadily gains transparency in most patients and are sufficient for restoring visual acuity. CrossRefPubMedGoogle Scholar
- 6.•• Fagerholm P, Lagali NS, Ong JA, Merrett K, Jackson WB, Polarek JW, et al. Stable corneal regeneration four years after implantation of a cell-free recombinant human collagen scaffold. Biomaterials. 2014;35:2420–7. https://doi.org/10.1016/j.biomaterials.2013.11.079. This study suggests that RHC stromal scaffolds may seem to be the currently most-advanced clinical method for biosynthesizing stromal substitutes. CrossRefPubMedGoogle Scholar
- 7.• Hariya T, Tanaka Y, Yokokura S, Nakazawa T. Transparent, resilient human amniotic membrane laminates for corneal transplantation. Biomaterials. 2016;101:76–85. https://doi.org/10.1016/j.biomaterials.2016.05.038. This study suggests that laminated, cross-linked amnion membrane has high transparency, high resistance to piercing damage, and high biocompatibility. CrossRefPubMedGoogle Scholar
- 16.Fagerholm P, Lagali NS, Merrett K, Jackson WB, Munger R, Liu Y, et al. A biosynthetic alternative to human donor tissue for inducing corneal regeneration: 24-month follow-up of a phase 1 clinical study. Sci Transl Med. 2010;2:46–61. https://doi.org/10.1126/scitranslmed.3001022.CrossRefGoogle Scholar
- 18.Yumoto H, Hirota K, Hirao K, Miyazaki T, Yamamoto N, Miyamoto K, et al. Anti-inflammatory and protective effects of 2-methacryloyloxyethyl phosphorylcholine polymer on oral epithelial cells. J Biomed Mater Res A. 2015;103:555–63. https://doi.org/10.1002/jbm.a.35201.
- 19.Tanaka Y, Baba K, Duncan TJ, Kubota A, Asahi T, Quantock AJ, et al. Transparent, tough collagen laminates prepared by oriented flow casting, multi-cyclic vitrification and chemical cross-linking. Biomaterials. 2011;32:3358–66. https://doi.org/10.1016/j.biomaterials.2010.11.011.CrossRefPubMedGoogle Scholar
- 20.Tanaka Y, Kubota A, Yamato M, Okano T, Nishida K. Irreversible optical clearing of sclera by dehydration and cross-linking. Biomaterials. 2011;32:1080–90. https://doi.org/10.1016/j.biomaterials.2010.10.002.CrossRefPubMedGoogle Scholar
- 21.Tanaka Y, Shi D, Kubota A, Takano Y, Fuse N, Yamato M, et al. Irreversible optical clearing of rabbit dermis for autogenic corneal stroma transplantation. Biomaterials. 2011;32:6764–72. https://doi.org/10.1016/j.biomaterials.2011.05.081.CrossRefPubMedGoogle Scholar