Bioengineered Cornea Implants from Pig Skin 👁

Judging from the title, you may think “ew, it’s weird” but it would certainly be life-changing for others!

Did you know? According to the World Health Organization (WHO) (2021), at least 2.2 billion individuals worldwide suffer from near- or distant vision impairment due to problems located in the cornea. Nearly half of these instances, or at least 1 billion, involved visual damage that either might have been avoided or is still unaddressed. Corneal blindness is the fourth most common cause of blindness in the world. It is anticipated that population expansion and aging will increase the likelihood that more people may get visual impairment. Low- and middle-income countries have a four times greater prevalence of distant vision impairment than high-income ones (GBD 2019 Blindness and Vision Impairment Collaborators, 2020). In terms of near vision, rates of untreated close vision impairment are estimated to be higher than 80% in Africa, compared to rates that are believed to be lower than 10% in high-income regions (North America, Australasia, etc.) (Bourne et al., 2021).

The eye is one of the essential organs that allows you to see, helps to send visual information to your brain, and serves a crucial role in protecting us from harm, particularly when our other senses are impaired (Artal, 2014). Diving deeper into the eyes, we have the cornea! The cornea, which makes up the frontmost portion of the eyeball, is a transparent component of the eye (Tandon et al., 2019).

Figure 1. Anatomy of an eye (cancer.gov)

The cornea is imperative in the eye as it serves several roles, including safeguarding internal organs, enhancing refractive ability, and concentrating light on the retina with the least amount of scatter and optical deterioration (Sridhar, 2018).

A corneal transplant, or keratoplasty, still remains one of the best treatments for corneal blindness that is usually taken from human donors (Tandon et al., 2019). The most common reason for corneal transplants is keratoconus, which causes the cornea to thin and protrude outward (Santodomingo-Rubido et al., 2022). However, only 1 in 70 persons in need of a corneal transplant will actually receive one due to a LACK of appropriate donor corneas, and the biggest prevalence of corneal blindness happens in low- to middle-income countries with inadequate transplant infrastructure (William & Muir, 2018). In addition, the possibility of spreading viruses and infectious illnesses, nevertheless, is a significant factor in corneal transplantation that can impact both recipients and those handling donor tissue which is further contributed by the sudden appearance of COVID-19; it had a catastrophic effect on corneal transplantation globally (Ang et al., 2020). Hence, researchers have been focused on bioengineering tissue that is appropriate for corneal transplantation to solve the issue of the scarcity of transplantable corneas. Researchers were able to engineer cell-free corneal tissue using collagen taken from pig skin that was gathered as a byproduct (waste!) of the food industry.

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Why Pigs?

It is because they have similar physiology to humans, develop quickly in the laboratory, and only take a few months for it to mature into a transplantable size. In addition, its collagen is also FDA approved (Dolgin, 2021).

How is it Created?

A non-toxic chemical cross-linker that is water soluble and washes out of the implant is used to rehydrate and crosslink the pure collagen. It only has one function, which is to join the collagen fibers together to strengthen the implant. The implant is then subjected to UVA light in a second process, where the addition of a little quantity of riboflavin (vitamin B2) further photochemically bonds the collagen fibers, creating an extremely strong implant that is a hydrogel with approximately 90% water. Furthermore, the bioengineered implants were also certified and approved to ensure that they are non-toxic, non-irritating, and safe to use. In addition, they have a longer shelf life of about two years compared to human donor tissue of one to two weeks (Rafat et al., 2022).

The Results......

It was first tested in pigs and it was found that six months after the surgery, none of the five pigs' corneas significantly deteriorated or changed in thickness; they all continued to be transparent hinting the success of these corneas. Following a fruitful test in pigs, the researchers moved on to examine the corneal implants in people with keratoconus. In Iran and India, where corneal blindness is frequent and there is a paucity of donated corneas, the implants were placed to the native corneal tissue of 20 keratoconus patients using laser-assisted surgery. The treatment is minimally invasive since only a tiny incision (other words: small cut!) is needed to input the biosynthetic pig collagen cornea rather than removing the old cornea and replacing it. After several months, all of the patients' visions improved and even three achieved a perfect vision (Rafat et al., 2022).

Figure 2. Slit-lamp photographs pre-operatively (left) and one day post-operative (with the pig-skin cornea) (right) with arrows indicating immediate change in thickness and curvature in the central cornea (Rafat et al., 2022)

Future Significance?

Bioengineered implants might greatly lower the need for donor corneal tissue in the future because keratoconus is a prominent cause of corneal transplantation in many parts of the world, including Europe, Australia, and Asian nations (Liu et al., 2022). Lastly, since it can be delivered almost anywhere and kept chilled until use, it may be able to help those who do not have easy access to eye care. This makes the process accessible to plenty of urban locations and rural regions without eye banks (Gain et al., 2016).

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References

• Ang, M., Moriyama, A., Colby, K., Sutton, G., Liang, L., Sharma, N., Hjortdal, J., Shun Chiu Lam, D., P Williams, G., Armitage, J., & S Mehta, J. (2020). Corneal transplantation in the aftermath of the COVID-19 pandemic: an international perspective. British Journal of Ophthalmology, bjophthalmol-2020. https://doi.org/10.1136/bjophthalmol-2020-317013

• Artal, P. (2014). Optics of the eye and its impact in vision: a tutorial. Advances in Optics and Photonics, 6(3), 340. https://doi.org/10.1364/aop.6.000340

• Bourne, R., Steinmetz, J. D., Flaxman, S., Briant, P. S., Taylor, H. R., Resnikoff, S., Casson, R. J., Abdoli, A., Abu-Gharbieh, E., Afshin, A., Ahmadieh, H., Akalu, Y., Alamneh, A. A., Alemayehu, W., Alfaar, A. S., Alipour, V., Anbesu, E. W., Androudi, S., Arabloo, J., . . . Vos, T. (2021). Trends in prevalence of blindness and distance and near vision impairment over 30 years: an analysis for the Global Burden of Disease Study. The Lancet Global Health, 9(2), e130–e143. https://doi.org/10.1016/s2214-109x(20)30425-3

• Dolgin, E. (2021). First GM pigs for allergies. Could xenotransplants be next? Nature Biotechnology, 39(4), 397–400. https://doi.org/10.1038/s41587-021-00885-9

• Gain, P., Jullienne, R., He, Z., Aldossary, M., Acquart, S., Cognasse, F., & Thuret, G. (2016). Global survey of corneal transplantation and eye banking. JAMA Ophthalmology, 134(2), 167. https://doi.org/10.1001/jamaophthalmol.2015.4776

• GBD 2019 Blindness and Vision Impairment Collaborators. (2020, December). Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: The right to sight: An analysis for the global burden of disease study. The Lancet Global Health. Retrieved September 15, 2022, from https://doi.org/10.1016/S2214-109X(20)30489-7

• Liu, S., Wong, Y. L., & Walkden, A. (2022, March). Current perspectives on corneal transplantation. Clinical Ophthalmology, 16, 631–646. https://doi.org/10.2147/opth.s289359

• Rafat, M., Jabbarvand, M., Sharma, N., Xeroudaki, M., Tabe, S., Omrani, R., Thangavelu, M., Mukwaya, A., Fagerholm, P., Lennikov, A., Askarizadeh, F., & Lagali, N. (2022). Bioengineered corneal tissue for minimally invasive vision restoration in advanced keratoconus in two clinical cohorts. Nature Biotechnology. https://doi.org/10.1038/s41587-022-01408-w

• Santodomingo-Rubido, J., Carracedo, G., Suzaki, A., Villa-Collar, C., Vincent, S. J., & Wolffsohn, J. S. (2022). Keratoconus: An updated review. Contact Lens and Anterior Eye, 45(3), 101559. https://doi.org/10.1016/j.clae.2021.101559

• Sridhar, M. (2018). Anatomy of cornea and ocular surface. Indian Journal of Ophthalmology, 66(2), 190. https://doi.org/10.4103/ijo.ijo_646_17

• Tandon, R., Singh, R., Gupta, N., & Vanathi, M. (2019). Corneal transplantation in the modern era. Indian Journal of Medical Research, 150(1), 7. https://doi.org/10.4103/ijmr.ijmr_141_19

• Williams, A., & Muir, K. (2018). Awareness and attitudes toward corneal donation: challenges and opportunities. Clinical Ophthalmology, 12, 1049–1059. https://doi.org/10.2147/opth.s142702

• World Health Organization (WHO). (2021, October 14). Vision impairment and blindness. Retrieved September 15, 2022, from https://www.who.int/news-room/fact-sheets/detail/blindness-and-visual-impairment