Ophthalmic Bioengineering and Biomaterials

The biomaterials developed in this project are used as templates (membranes, scaffolds, or coatings) for developing biomaterial-cells constructs as components of novel cell-based therapies, and therefore the project is essentially linked to many of the projects included in the Ophthalmic Cellular Therapies program.  We apply our knowledge of polymer chemistry to create engineered biomaterials that promote and maintain the attachment and growth of corneal and retinal cells, as part of developing new therapies for treating disorders of the ocular surface and retina. The materials for making these templates are certain proteins (fibroin and sericin) that we isolate from the domesticated silkworms. We were the first to propose and report the silk proteins as biomaterials in ophthalmology. Further work is currently carried out for the functional optimization of such materials. We have also embarked on creating new synthetic substrates for growing retinal cells.

Despite many manufacturers of surgical adhesives in the world, there is no truly effective product on the market able to provide satisfactory clinical results. We are developing adhesive systems based on a protein isolated form silk cocoons, sericin, which displays adhesive properties in its native state. Two-component adhesive systems are created by modifying the structure of sericin in such a way that, after being placed within tissues at the surgical site, it will become a gel by exposure to UV radiation, able to maintain the tissue parts glued. We are also developing one-component adhesives starting from an amino acid and inspired by the mussel adhesive protein, the strongest adhesive in nature. In experiments with commercial meat specimens, our products displayed adhesivity, and currently we work to upgrade such properties. Both routes involve rather sophisticated chemical synthesis techniques and advanced testing methodology. In this project we collaborate with Queensland University of Technology, University of Queensland and University of Western Australia.

Hyaluronic acid (HA) is extensively used as a dermal filler in cosmetic surgery. There is an increasing volume of reports about patients becoming blind following facial injection of HA, due to retinal ischemia caused by the occlusion of certain retinal arteries by the particles of dermal filler, in this case HA. The only therapeutic strategy proposed so far consists of a fast action to degrade the injected HA. We are investigating the validity of this approach in our laboratories by experimental degradation of HA using ultrasound, hyaluronidase (the enzyme that naturally degrades HA), or their combined action.

Silk sericin and/or associated non-sericinoid substances have been suggested as possessing antioxidant activity in biological processes, but the results so far are controversial. This would be important in protecting retinal cells from oxidative stress, which is implicated in the degenerative retinal pathologies. In our previous research, we found that sericin isolated from the cocoons of normal Bombyx mori silkworm does not display such effects. This project will study the effects of the sericin isolated from a mutant silkworm (produced in Japan and known as “Sericin Hope” race) that is able to produce exclusively sericin. The isolation procedure of this type of sericin, the extraction of associated substances, and the manufacture of sericin substrates have been established in our laboratories. Retinal photoreceptor cells will be cultured on these substrates and the effect of sericin will be assessed in the presence or absence of induced oxidative stress.