Addressing preventable blindness equitably and sustainably through bioengineering

Bioengineering holds promise in developing tissues to treat disease without needing to source donor tissue or organs. Alongside materials engineering, surgery, and wound healing, sustainable production and access to under-served populations are equally important considerations.
Addressing preventable blindness equitably and sustainably through bioengineering

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In our article published this week in Nature Biotechnology, we describe our work aiming to address a major cause of preventable blindness.1 According to the World Health Organization, over 80% of global visual impairment is preventable, yet 90% of those who are blind or visually impaired live in low- and middle-income countries (LMICs) where access to eye care is extremely poor.2 Recognizing this, in July 2021 the United Nations General Assembly adopted the first-ever resolution on eye health as part of the Sustainable Development Goals. This resolution commits us to reach 1.1 billion people with vision impairment who presently lack access to eye care, by 2030.3

Achieving progress towards this goal will require a radical rethinking of how eye care is delivered globally. The solution will undoubtedly be multi-faceted, and biomedical innovations may be an important piece of the puzzle. Our research focuses on corneal visual impairment and blindness, which affects millions worldwide and with an especially dire situation in LMICs.4,5 The cornea is the clear outer ‘window’ of the eye, which when diseased can lose its clarity, often requiring transplantation to prevent blindness. Challenges, however, in treating corneal blindness include: i) sourcing donor cornea tissue in adequate quantities; ii) delivering the tissue to where it is needed when it is needed; and iii) performing complex and potentially risky transplantation surgery needed to restore vision.

Our team, as well as other teams around the world, are focusing on the first of these challenges by bioengineering tissue to address the global shortage of donor corneas and limitations of human allogeneic tissue. The remaining challenges of access and delivery of care, however, are arguably equally important, but unfortunately these have received much less attention.

Around 2012, we recognized the need for large-scale bioengineering of corneal tissue at low cost using sustainably sourced raw materials. Instead of developing novel synthetic molecules and complex materials on a small scale (and at high cost) in a laboratory, we chose to use only natural collagen from porcine skin (which is an abundant waste product derived from the food industry) to ensure that high volumes of tissue could be produced at low cost (the native cornea is composed mainly of collagen as the extracellular matrix). Simplicity of the raw materials is also key to feasibly manufacturing engineered tissues on a large scale. Essential for our paper was the long-term development work of biomaterials engineer and entrepreneur Mehrdad Rafat (first author on the paper) and the spinoff company LinkoCare Life Sciences AB. Meeting the numerous and stringent production and testing requirements for a class III implantable medical device is an enormous undertaking, particularly for soft hydrogels, a relatively new class of implantable materials.

The development and manufacturing of implantable devices could not feasibly be accomplished within the scope and resource constraints of academia. A spinoff company with its own private investment, employees, and dedicated grant funding was therefore essential. Key advances made by the company were the stabilization of the collagen using multiple crosslinking methods and achieving stringent quality control, manufacturing, sterilization, and packaging to ensure the engineered tissue not only survived human implantation but could be shipped and stored for years without a decline in performance. These aspects are vital for dissemination of the technology globally, to LMICs and remote areas which lack infrastructure for procuring, handling, testing, and storing human donor tissues.

Long-term research funding was also critical for our work, in particular a five-year project funded by the European Union's Horizon 2020 framework program. The project provided numerous benefits in terms of support for research personnel, preclinical studies, developing quality manufacturing processes, and ethical, scientific and regulatory oversight by independent experts and panels.   

At the same time as the first prototypes were being produced by the company using purified porcine collagen, we explored options for a simplified surgery to implant the tissue. The limitations of traditional corneal surgery in implanting bioengineered tissue were apparent from our earlier work,6 where the wound healing response was aggressive and led to melting and scarring, rehabilitation time was long, and patients required many hospital visits for follow-up. In preclinical models, we often found that when an engineered biomaterial was placed into the eye but remained exposed to the external environment (tear film, eyelids and air), it quickly degraded or stimulated the native cornea to produce scar tissue. Protecting the material from the external environment was thus essential, and we experimented with different implantation techniques.7,8 We discovered that implanting a material within the cornea while leaving a thin layer of the native tissue above and below the material preserved the integrity, shape, and transparency of the biomaterial and of the surrounding cornea. An added advantage was that the surgery did not require suturing and did not trigger a strong inflammatory or wound healing response, resulting in quick healing without prolonged use of immune-suppressing medications like corticosteroids. This would mean that in theory a single procedure and hospital visit could suffice. The surgery could thicken and reshape the cornea and we soon realized it could be used as a safer, less invasive, and simpler alternative to current surgical treatment for advanced keratoconus, a disease affecting millions in LMICs.4,5  What surprised us was how well this approach worked to restore vision to subjects who were initially blind with advanced keratoconus and who could not tolerate contact lenses. We did not specifically match the shape, thickness or size of the engineered implants for the particular subject, but no person was blind after the procedure, and three initially blind subjects attained 20/20 vision. All subjects also regained tolerance to contact lens wear.

Bioengineered corneal implant made from collagen sourced from porcine skin. Courtesy of LinkoCare Life Sciences AB, Sweden. Photo: Thor Balkhed/Linköping University.

Our work in a broader sense demonstrates that a human tissue can be bioengineered and used to treat a widespread disease, with safety and efficacy at least on par with traditional treatment. As our cell-free scaffold can be repopulated by host cells in vivo, it is suggestive that more complex tissues and even organs could be engineered by providing a suitable scaffold with or without cells; this goal is presently being pursued by many research teams. Ideally, the implantation surgery should not induce an excessive immune or wound healing response, to maintain integrity of the implanted biomaterial. In our study the implantation method was essential for restoring vision; in other applications one should consider whether removing and replacing an entire tissue or organ is necessary. Simpler and less invasive approaches could possibly restore function to existing tissues and organs and may be less demanding for patients. Moreover, shipping and delivering off-the-shelf tissues that can be stored for long time periods at room temperature or in a refrigerator will enable new technologies to reach a much wider recipient population.

We are enthusiastic for the future, as we work towards delivering this technology at low cost to those in most need. We also hope that the bioengineering field will prioritize the use of sustainable materials, while also including cost, access to technology and equitable healthcare for everyone within the bioengineering design constraints.


  1. Rafat M, Jabbarvand M, Sharma N, Xeroudaki M, Tabe S, Omrani R, Thangavelu M, Mukwaya A, Fagerholm P, Lennikov A, Askarizadeh F, Lagali N. Bioengineered corneal tissue for minimally invasive vision restoration in advanced keratoconus in two clinical cohorts. Nat Biotechnol. (2022).

  2. WHO Action plan for the prevention of avoidable blindness and visual impairment for 2014–2019,, Accessed 6 July 2022.
  3. Vision for Everyone: accelerating action to achieve the Sustainable Development Goals, Resolution A/75/L.108 adopted 23 July 2021,
  4. Mathews, P.M., Lindsley, K., Aldave, A.J. & Akpek, E.K. Etiology of Global Corneal Blindness and Current Practices of Corneal Transplantation: A Focused Review. Cornea. 37, 1198-1203 (2018).
  5. Gain, P., Jullienne, R., He, Z., Aldossary, M., Acquart, S., Cognasse, F., et al. Global survey of corneal transplantation and eye banking. JAMA Ophthalmol. 134, 167–73 (2016).
  6. Fagerholm P, Lagali NS, Merrett K, Jackson WB, Munger R, Liu Y, Polarek JW, Söderqvist M, Griffith M. A biosynthetic alternative to human donor tissue for inducing corneal regeneration: 24-month follow-up of a phase 1 clinical study. Sci Transl Med. 2:46ra61 (2010).
  7. Koulikovska M, Rafat M, Petrovski G, Veréb Z, Akhtar S, Fagerholm P, Lagali N. Enhanced regeneration of corneal tissue via a bioengineered collagen construct implanted by a nondisruptive surgical technique. Tissue Eng Pt A. 21, 1116-30 (2015).
  8. Xeroudaki M, Thangavelu M, Lennikov A, Ratnayake A, Bisevac J, Petrovski G, Fagerholm P, Rafat M, Lagali N. A porous collagen-based hydrogel and implantation method for corneal stromal regeneration and sustained local drug delivery. Sci Rep. 10, 16936 (2020). 

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