Ophthalmic bioengineering develops innovative materials, processes and devices for the prevention, diagnosis and treatment of eye diseases, based on principles of engineering. As an essential part of it, the biomaterials can be generally defined as artificial or natural materials (other than drugs) that are developed to be inserted into the human body with a precise diagnostic or therapeutic aim.
An ophthalmic biomaterial must interface with the biological system of the eye with an aim to treat, augment or replace any of its segments.
Our research program for applying bioengineering and biomaterials in developing therapeutic procedures for the eye includes: methods and materials to make templates for growing a variety of the eye’s cells; new treatments for ocular pathologies; materials for surgical and post-surgical applications.
A substantial amount of experimental work is dedicated to investigating the compatibility and safety of biomaterials when placed into the eye, as well as to basic work pertaining polymer science.
The program currently consists of the research projects described further.
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.
The Floppy Eyelid Syndrome (FES) is a disorder generated by the laxity of the eyelid, when its inherent rigidity is lost. Due to complications, a floppy eyelid is a potentially blinding condition. The treatment methods used so far could not prevent the recurrence of symptoms. We are developing a procedure based on the stiffening of the eyelid’s tarsal plate, achievable through the photochemical crosslinking of tarsal collagen induced by exposure to UVA radiation. We have proved the validity of this concept in animal eyelids, and the results laid foundation to patent protection and to publications in the premier journal of oculoplastic surgery. We have recently established the safety range for the radiation exposure of the tissue. Evaluation in donor human eyelids is currently in preparation.
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.
Patients in preparation for ophthalmic or other types of surgery, or endoscopic investigations, or blood tests are required to fast for at least 4-6 hours, and have to follow strictly a nil-by-mouth period. In such circumstances, a habitual coffee drinker is unable to drink coffee or any caffeinated beverage, and this may result in unwanted caffeine withdrawal symptoms in the patient. We have developed a system for delivery of caffeine through an intranasal route, allowing the direct transport of absorbed caffeine, together with associated flavouring substances, into systemic circulation or into the central nervous system, such avoiding the first-pass metabolism in the gastrointestinal tract. That will allow the patients to have their necessary input of caffeine prior to a medical intervention, and prevent withdrawal symptoms. A nasal spray was developed in our laboratories, the conditions for its small-scale production have been established, and patent protection processed. It is expected that the product will be soon available to patients.
Following eye surgery, an external dressing, as a pad or mask, is necessary. The material shall fulfil certain stringent requirements, such as flexibility, soothing effect postoperatively, retention of water, permeability for oxygen, etc. Our aim is to develop polymeric hydrogels as hydrogel pads that can function as sterile and antimicrobial dressings when applied on the operated eyes of patients. Presently, such pads are imported from overseas. A large series of crosslinked have been synthesized in our laboratories and combined with natural polymers to generate hydrogels that have fulfilled the requirements better than the imported products. Studies are planned to improve resistance to gamma-sterilization of selected hydrogels, and to assess their loading with antimicrobial agents.
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.