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The Research of Miguel González-Andrades

Miguel González-Andrades, MD, PhD.


I am a clinician-scientist currently working as an ophthalmologist and research scientist in the Ophthalmology Unit at Reina Sofia University Hospital and Maimonides Biomedical Research Institute of Córdoba (Córdoba, Spain), and as adjunct scientist in the Keratoprosthesis Group at the Schepens Eye Research Institute and Mass Eye and Ear Infirmary (SERI-MEEI), Harvard Medical School (Boston, USA).

Since the beginning of my academic training, I have demonstrated a clear commitment to a career in Tissue Engineering and Regenerative Medicine, with the ultimate goal of finding suitable treatments for corneal blind patients. My interest in corneal tissue engineering dates back to my years as a medical student, when I started working on generating human corneal substitutes through the application of Tissue Engineering techniques in the Tissue Engineering Group of the University of Granada, Spain, where I obtained my PhD (summa cum laude, Doctor Europeus). I successfully completed my training in ophthalmology, receiving the Arruga Award (from the Spanish Society of Ophthalmology) to the best Spanish ophthalmologists under 40. In 2017, I obtained the prestigious Claes Dohlman Fellowship Award that internationally recognizes outstanding fellows training in the specialty area of Cornea and External Diseases.

After 4 years as postdoctoral researcher at SERI-MEEI, I received a K99/R00 grant from NIH in 2018 to facilitate my independency and create my own research lab, in addition to faculty promotion (sadly, I had to decline the grant because of family reasons). I have also participated in different European initiatives such as the COST action “Joining Forces in Corneal Regeneration Research”, being also involved in the European Society of Ophthalmology (I am the current chair of the young ophthalmologist section of the society).


Corneal diseases are one of the most important causes of blindness in the world.1,2 Over 90% of people with bilateral corneal blindness live in developing countries, where there is a shortness of corneal transplant readiness.3,4 Furthermore, many of these eyes are at high risk of failure with traditional donor penetrating keratoplasty due to deep vascularization and/or limbal stem cell deficiency.5 In this context, biomedical engineering, and specifically tissue engineering, emerges with the ambition of generating artificial corneas that lead to the functional restoration of the human cornea, overcoming those major drawbacks of corneal transplants. My contributions to generate an artificial substitute of the human cornea have been based on the development and optimization of different types of corneal scaffolds and prosthesis:

Fibrin-agarose scaffolds:

We were able to develop and characterize fibrin-agarose scaffolds containing cultured human corneal epithelial cell and fibroblast (patent WO-2011023843-A3).6 Afterwards, I coordinated a multicenter T1-2 phase clinical trial (EudraCT: 2010-024290-40) to evaluate the safety and partial efficacy of fibrin-agarose scaffolds in patients with severe corneal ulcers. This clinical trial was the first one in the world evaluating an artificial cornea based on a tissue engineered scaffold containing two different cultured corneal cell populations (Figure 1).7

Figure 1: Anterior segment optical coherence tomography of a patient showing the implanted fibrin-agarose scaffold after removal of the damaged tissue of the recipient cornea.

Collagen scaffolds:

In collaboration with Prof. Robert Brown (University College of London, UK), we developed new strategies for increasing the transparency of collagen-based corneal subtitutes. For that purpose, we generated multilayered collagen scaffolds based on a multilayering plastic compression technique and achieved higher levels of transparency compared to non-multilayered collagen scaffolds. Additionally, we developed an inexpensive and simple method to evaluate the optical properties of artificial tissues based on imaging analysis.8 Independently of this work, I collaborated with Prof. Che Connon (Newcastle University, UK), developing a self-lifting auto-generated tissue equivalent (SLATE) for corneal graft. We controlled the phenotype of corneal stromal cells and instruct them to fabricate self-lifting tissues that closely emulated the native stromal lamellae of the human cornea using multi-functional peptide amphiphile-coated surfaces with different anisotropies.9

Decellularized xenografts:

The supply of corneal tissue for corneal transplants can be achieved if corneal xenografts, a permanent and accessible cheap source of tissue, are optimized to avoid rejection. One approach to accomplishing this is to remove animal cells from the animal cornea (via decellularization). To promote biointegration into the human host, it has been proposed that the decellularized xenograft can be seeded with human corneal cells from the patient (recellularization process). In this regard, we successfully described the recellularization process of decellularized porcine corneas with human corneal cells.10 Moreover, we optimized the decellularization process to apply to whole porcine corneas with sclerocorneal limbus.11 Because the sclerocorneal limbus is essential for corneal cell physiology and regeneration, this finding could be of interest for applications using limbal stem cells. Recently, we carried out a comparative analysis of corneal matrix proteins across species in order to find the most optimal corneal xenograft to be used in human patients.12 For that purpose, we compared the amino-acid sequences of 16 proteins present in the corneal stromal matrix of 14 different animal species using Basic Local Alignment Search Tool, and calculated a similarity score compared to the respective human sequence. Our results suggested that porcine cornea has a higher relative suitability for corneal transplantation into humans compared to other studied species, showing the highest similarity score (91.8%) to human corneas. At the moment, we are evaluating the effects of gamma radiation sterilization on the structural and biological properties of decellularized porcine corneas (Figure 2).

Figure 2: Porcine cornea after applying decellularization and gamma radiation sterilization.

Boston Keratoprosthesis:

The Boston Keratoprosthesis (B-KPro) has been successfully used to treat corneal blindness or eyes that are not suitable for standard corneal transplantation in more than 13,000 patients worldwide.13 The B-KPro is an artificial cornea made by polymethyl methacrylate. This device is cheaper than tissue engineering therapies, but still too expensive for most potential users and hospitals ($5,000 per prosthesis). There are two main challenges to be addressed associated to the B-KPro: the need of a donor corneal tissue as a carrier for the B-KPro implantation, which difficults the B-KPro implementation into the non-developed countries, as well as the postoperative complications directly associated to the B-KPro.14 In this regard, to make the B-KPro, together with its carrier corneal graft, more easily procured, transported and stored, as well as less expensive, easier for the surgeon to implant and safer for the patient, we proposed and optimized the pre-assembly of the B-KPro-graft combination, followed by sterilization with gamma radiation allowing long-term storage at room temperature.15 Furthermore, there is a need to improve the biointegration of the device in order to control the postoperative complications. In this sense, different wound healing mechanisms might be adopted to facilitate the B-KPro integration into the wounded cornea. Thus, we developed a novel in vitro model of human stratified epithelial wound healing with barrier function to study not only the molecular mechanisms involved in epithelial wound healing but also the interactions between biomaterials and cells.16


  1. Oliva MS, Schottman T, Gulati M. Turning the tide of corneal blindness. Indian J Ophthalmol 2012; 60(5): 423-7.
  2. Burton MJ. Prevention, treatment and rehabilitation. Community Eye Health 2009; 22(71): 33-5.
  3. WHO. Prevention of Blindness and Visual Impairment. (accessed 11 Nov 2017.
  4. Gain P, Jullienne R, He Z, et al. Global Survey of Corneal Transplantation and Eye Banking. JAMA Ophthalmol 2016; 134(2): 167-73.
  5. Islam M.M., Sharifi R., Gonzalez-Andrades M. (2019) Corneal Tissue Engineering. In: Alió J., Alió del Barrio J., Arnalich-Montiel F. (eds) Corneal Regeneration. Essentials in Ophthalmology. Springer, Cham.
  6. Gonzalez-Andrades M, Garzon I, Gascon MI, et al. Sequential development of intercellular junctions in bioengineered human corneas. J Tissue Eng Regen Med 2009; 3(6): 442-9.
  7. Gonzalez-Andrades M, Mata R, Gonzalez-Gallardo MDC, et al. A study protocol for a multicentre randomised clinical trial evaluating the safety and feasibility of a bioengineered human allogeneic nanostructured anterior cornea in patients with advanced corneal trophic ulcers refractory to conventional treatment. BMJ Open 2017; 7(9): e016487.
  8. Gonzalez-Andrades M, Cardona Jde L, Ionescu AM, Mosse CA, Brown RA. Photographic-Based Optical Evaluation of Tissues and Biomaterials Used for Corneal Surface Repair: A New Easy-Applied Method. PLoS One 2015; 10(11): e0142099.
  9. Gouveia RM, Gonzalez-Andrades E, Cardona JC, et al. Controlling the 3D architecture of Self-Lifting Auto-generated Tissue Equivalents (SLATEs) for optimized corneal graft composition and stability. Biomaterials 2017; 121: 205-19.
  10. Gonzalez-Andrades M, de la Cruz Cardona J, Ionescu AM, Campos A, Del Mar Perez M, Alaminos M. Generation of bioengineered corneas with decellularized xenografts and human keratocytes. Invest Ophthalmol Vis Sci 2011; 52(1): 215-22.
  11. Gonzalez-Andrades M, Carriel V, Rivera-Izquierdo M, et al. Effects of Detergent-Based Protocols on Decellularization of Corneas With Sclerocorneal Limbus. Evaluation of Regional Differences. Transl Vis Sci Technol 2015; 4(2): 13.
  12. Sharifi R, Yang Y, Adibnia Y, Dohlman CH, Chodosh J, Gonzalez-Andrades M. Finding an Optimal Corneal Xenograft Using Comparative Analysis of Corneal Matrix Proteins Across Species. Sci Rep 2019; 9(1): 1876.
  13. Aquavella JV, Qian Y, McCormick GJ, Palakuru JR. Keratoprosthesis: the Dohlman-Doane device. American journal of ophthalmology 2005; 140(6): 1032-8.
  14. Aldave AJ, Sangwan VS, Basu S, et al. International results with the Boston type I keratoprosthesis. Ophthalmology 2012; 119(8): 1530-8.
  15. Gonzalez-Andrades M, Sharifi R, Islam MM, et al. Improving the practicality and safety of artificial corneas: Pre-assembly and gamma-rays sterilization of the Boston Keratoprosthesis. Ocul Surf 2018; 16(3): 322-30.
  16. Gonzalez-Andrades M, Alonso-Pastor L, Mauris J, Cruzat A, Dohlman CH, Argueso P. Establishment of a novel in vitro model of stratified epithelial wound healing with barrier function. Sci Rep 2016; 6: 19395.
Miguel González-Andrades, MD, PhD.

Miguel González-Andrades, MD, PhD.

Ophthalmologist and Research Scientist,
Department of Ophthalmology,
Reina Sofia University Hospital and Maimonides Biomedical Research Institute of Cordoba (IMIBIC),
University of Cordoba,

Adjunct Scientist,
Massachusetts Eye and Ear and Schepens Eye Research Institute,
Department of Ophthalmology,
Harvard Medical School,
Boston, MA,

Email: mgandrades[at]