Challenges in tissue engineering

What type of constructs can be used for regeneration of the human cornea?

Dr. Mehrdad Rafat: Constructs that closely mimic the chemistry and microstructure of the human cornea. For example, collagen-based constructs with a balanced mechanical and cell-interactive   characteristics are ideal for regeneration of the cornea.

How popular is cornea regeneration by tissue engineering method?

 Dr. Mehrdad Rafat: Given the huge shortage of donor corneas and the low success rate of prosthetic corneas, tissue engineering has gained momentum and more research and development activities are focused on developing new methods to harness the regenerative power of the native tissue and help the cornea to heal itself rather than replacing it with fully synthetic constructs .

Could you explain step-by-step the procedure of cornea regeneration by tissue engineering method?

Dr. Mehrdad Rafat:  It is believed that cells, Extra Cellular Matrix (ECM) and growth-stimulating signals, also referred to as the Tissue Engineering Triad, are necessary key components for regeneration of any tissue. Cornea is not an exception and corneal cells (e.g. fibroblasts) need to attach and grow into ECM or ECM-mimetic constructs to be functional (e.g. produce proteins, growth factors, etc.) as well as being able to produce new collagen (definition of regeneration). In corneal tissue engineering, ECM-mimetic constructs are produced in the lab in cell-free form or combined with cells and growth factors and transplanted into patients’ eyes depending on the underlining causes of the blindness. The epidemiology of corneal blindness is complex and includes a wide range of infectious and inflammatory eye diseses that cause corneal blindness. As a result, the treatment method need to be tailored for each group of patients.

What are the benefits for patients with this method?

Dr. Mehrdad Rafat: Several research groups are working on Tissue Engineering (TE) or bioengineering of the cornea. I cannot speak for others but I can tell that our bioengineered corneas have several benefits including but not limited to: minimum risk of rejection, minimum need for post-surgical drugs, better biocompatibility and integration into the patient’s eyes than the synthetic corneas, permanent corneas, cost-effective, and more readily available to patients.

How high is the effectiveness of this method?

Dr. Mehrdad Rafat: Our animal studies and pilot clinical trials have suggested that our Bioengineered Corneas are quite effective, they remained transparent in vivo and have helped improving patients’ sight.

You co-invented the first clinically-tested bioengineered cornea. What has changed from that time?

 Dr. Mehrdad Rafat: I have been working in the field of bioengineering for almost 14 years during which I have faced enormous challenges and learned many lessons. Several things have changed since we invented the 1^st bioengineered cornea, for example, I shifted my focus from pure novelty and scientific aspects of the work to development aspects including innovation, validation, and fine-tuning of the technology, methods, and formulations, an approach that is only being practiced by a small group within the academic community. I also decided to simplify our protocols and secure cost-effective readily-available raw material sources ensuring my research is transferable to the industry and can be transformed into a product that will benefit all patients in the very near future. These changes have streamlined the commercialization process and paved the road to the market for the bioengineered cornea.

What are the most prominent achievements in area of tissue engineering?

Dr. Mehrdad Rafat: The past three decades have witnessed significant breakthroughs in the field of tissue engineering and regenerative medicine. In the 1980s, R&D in tissue engineering and biomaterials took off. Several biomedical engineering programs were established at main universities. In 1981, a tissue-engineered skin comprised of a porous collagen scaffold and a silicone cover was developed. The 1^st bone graft material was introduced in 1993. In 1999, the first successful tissue engineered bladder transplanted by Anthony Atala at Boston Children's Hospital in the U.S. We developed the 1^st bioengineered cornea at the University of Ottawa in Canada, a work in progress that is being continued at Linköping University in Sweden. Despite all the scientific advances, many of these technologies have not made it to the market yet due to the challenges faced by the tissue engineering industry including establishing Quality Control processes and facilities for mass production of these products under good manufacturing practice (GMP) conditions to meet regulatory standards. In the case of bioengineered cornea, our hope is that we can meet these challenges and produce corneas as a product in the next two years.

Which studies your research group currently focuses on?

Dr. Mehrdad Rafat: My research group’s interests are mainly focused on Biomaterials Engineering and development of cell-interactive bioengineered materials as implantable scaffolds for ocular and cardiovascular applications such as bioengineered corneas and cardiac patches and nano and microencapsulation systems for controlled delivery of stem cells, drugs, and proteins to target tissues. We are also trying to extend the application of our bioengineered materials, e.g. for nerve regeneration and cancer therapeutics. Our activities go beyond basic research and include translational research, evaluation, regulation, and GMP production and commercialization of biomaterials technologies and medical devices. I have founded a new spinoff company in Sweden (LinkoCare Life Sciences AB) to streamline commercialization of my research into products that will be available to and affordable by all patients inclding those less fortunate with limited purchasing power.

Thank you for the conversation.

Magdalena Zając