Tissue Engineering & Cell Therapy Programme is focused on:
Understanding and investigating the reconstruction and replacement of the cornea
Investigating the principles of corneal tissue engineering in order to improve surgical outcomes
Understanding the principles of in-vivo expansion of stem cells for the reconstruction of the cornea
Understanding through basic science and enabling the innovation in corneal tissue engineering and stem cell reconstruction towards translational corneal research.
1. Corneal Endothelial Cell Research
The human corneal endothelium (CE) is perhaps the most important layer of the cornea, physiologically. Although cells of the CE are unable to undergo any functional regeneration within the eye, studies have demonstrated the capacity for primary human CE cells to proliferate within a laboratory setting.
We have since further improved the cultivation of isolated human CE cells using a patented dual media culture system. The cultivated human CE cells can be consistently propagated to the third passage and can retain characteristic cellular morphology and expression markers indicative of the human CE layer. This has enabled down-stream development of potential graft alternatives through tissue-engineering. We are currently conducting a regulatory-approved first-in-man clinical trial using these expanded human CE cells.
Concurrently, we are also looking at the use of various constructs (both synthetic and biological) as potential scaffolds for tissue engineering, while characterising the growth of the cultivated human CE cells on each of these constructs. We are also looking at ways to improve the culture of human CE cells using different regulatory-approved small molecules that have shown potential in improving the adherence and/or the proliferation of cultivated human CE cells.
2. Ocular Surface Stem Cell Reconstruction
The presence of a smooth ocular surface is vital for normal vision. The corneal epithelium is the outermost region of the cornea and primarily serves to protect the eye. Its renewal relies on limbal stem cells. Their destruction is a major debilitating cause of ocular morbidity.
Transplantation to replace the damaged corneal epithelium can principally restore the vision, but allogeneic transplants in patients with bilateral disease do not have satisfactory long-term treatment due to the persistent use of immunosuppression.
We are examining the role of other autologous cell sources to develop a safe, stable, effective and functional tissue-engineered construct for patients with bilateral ocular surface disease.
3. Artificial Cornea
Artificial corneas (or keratoprostheses) are commonly used, especially for chronic inflammatory and ocular surface diseases. However, keratoprosthesis technology is still lacking — these devices utilise older polymers and outdated designs.
The Osteo-odonto keratoprosthesis (OOKP) is reserved for more severe ocular surface diseases, and has a high rate of device retention, but requires a highly complex surgery to remove an autologous tooth. Our team’s goal is to develop a synthetic OOKP-type device that does not require a tooth. This will significantly improve the time for visual rehabilitation in patients requiring this surgery, as well as simplify the surgical procedure tremendously.
Our previous work shows that TiO2 has excellent biocompatibility as a substrate to support cornea fibroblast integration, enhanced surface cell spreading and adhesion. We are developing a semi-flexible carbon mesh skirt for a synthetic OOKP artificial cornea.
4. Femtosecond Laser-Assisted Ocular Surgery
The use of femtosecond lasers has revolutionised the way clinicians perform refractive surgery. The laser has become an important tool to perform accurate and fine dissections with minimal collateral damage to the ocular tissues.
The main work to date in this area of study is focused on the investigation of laser-ocular tissue interactions, the optimisation of laser technology in performing myopic ReLEx (refractive lenticule extraction) and various keratoplasties, as well as the tissue engineering of an extracted lenticule from ReLEx as corneal inlay to restore corneal volume and, in the future, to correct presbyopic errors.
A. Whole-mount ß3-tubulin staining of cornea after undergoing LASIK procedure.
B. Helium ion micrograph of a crater on corneal stromal bed, created by a cavitation bubble during femtosecond laser photodisruption process.
C. In vivo confocal micrograph of femtosecond laser photodisrupted plane (reflective layer) and side cut (reflective line).
D. Topography of rabbit cornea captured by handheld video keratographer.
5. Anterior Segment Drug Delivery Systems
We have developed a biodegradable, prednisolone acetate-loaded microfilm made of poly (d,l-lactide-co-ε-caprolactone) (PLC). This drug delivery system can deliver sustained and therapeutic drug levels to the anterior segment for over four weeks. Therefore, it eliminates patient compliance and a dependency on a frequent dosing regimen after surgery. It also circumvents the limitations of conventional eye drops, such as low bioavailability and a short duration of action.
We have demonstrated that this novel microfilm has good biocompatibility and surgical feasibility in animal models. The implantation of the microfilm into the subconjunctival space is a single, simple and non-invasive procedure. The microfilm degrades to non-toxic metabolites over time; hence no extra procedure is needed to remove the implant after the depletion of the drug. Furthermore, the microfilm can be customised to deliver different drug release profiles, depending on different clinical scenarios.
Chin JY, Lin MT, Lee IXY, Mehta JS, Liu YC. Tear Neuromediator and Corneal Denervation Following SMILE. J Refract Surg. 2021 Aug;37(8):516-523. doi: 10.3928/1081597X-20210423-01. Epub 2021 Aug 1. PMID: 34388069.
Riau A, Boey K, Binte M Yusoff NZ, Goh TW, Yam G, Tang KF, Phua C, Chen HJ, Chiew YF, Liu YC, Mehta J. Experimental-based Validation of Corneal Lenticule Banking in a Health Authority-licensed Facility. Tissue Eng Part A. 2021 Jun 15. doi: 10.1089/ten.TEA.2021.0042. Online ahead of print. PMID: 34128385.
Liu YC, Yam GH, Lin MT, Teo E, Koh SK, Deng L, Zhou L, Tong L, Mehta JS. Comparison of Tear Proteomic and Neuromediator Profiles Changes between Small Incision Lenticule Extraction (SMILE) and Femtosecond Laser-assisted In-situ Keratomileusis (LASIK). J Adv Res. 2020 Nov 5;29:67-81. doi: 10.1016/j.jare.2020.11.001. eCollection 2021 Mar. PMID: 33842006.
Stapleton F, Lim CHL, Kweon S, Tan D, Mehta JS; ACSIKS group. Cosmetic Contact Lens-related Corneal Infections in Asia. Am J Ophthalmol. 2021 Mar 13;229:176-183. doi: 10.1016/j.ajo.2021.03.005. Online ahead of print. PMID: 33727002.
Riau AK, Htoon HM, Alió Del Barrio JL, Nubile M, El Zarif M, Mastropasqua L, Alió JL, Mehta JS. Femtosecond Laser-assisted Stromal Keratophakia for Keratoconus: A Systemic Review and Meta-analysis. Int Ophthalmol. 2021 May;41(5):1965-1979. doi: 10.1007/s10792-021-01745-w. Epub 2021 Feb 20. PMID: 33609200.
Ting DSJ, Peh GSL, Adnan K, Mehta JS. Translational and Regulatory Challenges of Corneal Endothelial Cell Therapy: A Global Perspective. Tissue Eng Part B Rev. 2021 Jan 11. doi: 10.1089/ten.TEB.2020.0319. Online ahead of print. PMID: 33267724.
Lovatt M, Kocaba V, Hui Neo DJ, Soh YQ, Mehta JS. Nrf2: A Unifying Transcription Factor in the Pathogenesis of Fuchs' Endothelial Corneal Dystrophy. Redox Biol. 2020 Oct;37:101763. doi: 10.1016/j.redox.2020.101763. Epub 2020 Oct 16. PMID: 33099215.
Soh YQ, Peh GSL, Naso SL, Kocaba V, Mehta JS. Automated Clinical Assessment of Corneal Guttae in Fuchs Endothelial Corneal Dystrophy. Am J Ophthalmol. 2021 Jan;221:260-272. doi: 10.1016/j.ajo.2020.07.029. Epub 2020 Jul 28. PMID: 32730910.
Liu YC, Ang M, Ong HS, Wong TY, Mehta JS. SARS-CoV-2 Infection in Conjunctival Tissue. Lancet Respir Med. 2020 Jul;8(7):e57. doi: 10.1016/S2213-2600(20)30272-1. PMID: 32649921.
Ong HS, Peh G, Neo DJH, Ang HP, Adnan K, Nyein CL, Morales-Wong F, Bhogal M, Kocaba V, Mehta JS. A Novel Approach of Harvesting Viable Single Cells from Donor Corneal Endothelium for Cell-injection Therapy. Cells. 2020 Jun 9;9(6):1428. doi: 10.3390/cells9061428. PMID: 32526886.
Principal Investigators & Clinician Scientist
Prof Jodhbir Mehta
Dr Liu Yu-Chi
Dr Ong Hon Shing
Dr Gary Peh
Research Fellows & Clinical Research Fellows
Dr Evan Wong
Dr Andri Kartasasmita Riau
Khadijah Binte Adnan
Nur Zahirah Bte M Yusoff
Neo Jing Hui, Dawn
Lin Tzu Yu, Molly
Nuur Shahinda Humaira
Lee Xin Yu, Isabelle
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