|
|
|
|
|
|
|
|
|
| CSIRO | SOLVE | Issue 13 | Jun 08 | |
|
| |||||||
ARTICLE
Scientists have developed a human tissue sealant that uses light to form a seal five times stronger and 50 times faster than existing tissue adhesivesHolding a bright torch, a doctor stands over a patient’s exposed brain. Shining the light on a liquid that has just been applied to the incision with the same ease as using a nail-polish applicator, the doctor watches as the edges of the membrane covering the brain (the dura) form a strong, bonded seam, a mere 15 seconds later.
While this type of wound sealing was once the material of sci-fi movies, astute observations about the chemical properties of a protein involved in wound healing have now made it a reality. The sealant arises from research by CSIRO's Dr Chris Elvin, who recently found a unique way to glue together the synthetic form of nature's ‘super rubber', resilin. The discovery of resilin, a protein, earned CSIRO researchers worldwide coverage in the prestigious journal Nature, in 2005. Through his work on resilin, Dr Elvin created a photochemical cross-linking technique that exploited the self-association or natural ‘gluing' properties of certain proteins. The photochemical cross-linking technique works by using a light source and metal-based chemicals to target the amino acid tyrosine within a protein. When a protein is made of a high percentage of tyrosines and mixed with the right chemicals, a chemical reaction – driven by the light source – can cause individual molecules of the protein to link together at the tyrosines and form a ‘web' of protein. Shortly after this discovery, Dr Elvin and his colleague and co-inventor of the new sealant technology, Dr Alan Brownlee, decided to investigate what other biologically important proteins could be cross-linked using this photochemical technique and how these cross-linked proteins would be medically useful. They soon found the answers to these questions in fibrinogen – a protein involved in blood clotting and tissue repair, which also contains a high proportion of tyrosines. Exploiting the ‘tyrosine rich' property of fibrinogen, the researchers used their cross-linking technology to form a ‘web' of fibrinogen – forming the basis of the light-activated ‘tissue glue', which they have called PhotoSeal™. While the medical industry has already found a way to use fibrinogen in tissue and blood vessel sealants, these early adhesive agents are expensive to produce and difficult to use. Based on the same enzymatic reactions that produce a blood clot, these fibrin-adhesives require multiple raw material proteins – including thrombin, Factor XII and fibrinogen – to produce their tissue-healing effects. Dr Elvin's and Dr Brownlee's novel photochemical cross-linking technology represents a generational advance. Their PhotoSeal™ is a tissue adhesive that sets 50 times faster and forms a seal that is five times stronger than the current commercially available tissue sealants. Dr Elvin says that a key benefit of PhotoSeal™ is its simplicity. “PhotoSeal™ really only has three ingredients: the protein fibrinogen, and two commercially available chemicals,” he says. “The cross-linking reaction is driven by a white light source, with intensity similar to the light used in a data projector. Such a small number of raw materials greatly reduces production costs.” Surgeons and industry have different needs, and PhotoSeal™ addresses these, says Dr Charles Lindall, CSIRO business development manager responsible for biomedical materials and regenerative medicine. “Our discussions with industry and surgeons have confirmed that there is certainly a need for improved sealants and surgical clamps. Surgeons want something that is easier to use and more effective in some applications, while industry wants a cost reduction in the production process and raw materials,” he says. Compared to fibrin-based sealants, which are applied to the injured tissue through a two pack system and take 15 to 20 minutes to cure, PhotoSeal™ achieves its maximum bond strength within 15 to 20 seconds of applying a strong light to it. Designed as a one-pack system, PhotoSeal™ is less likely to clog than the existing fibrin sealants because it does not set until a light is directly applied to the gel. PhotoSeal™ also excels in bond strength, as its seal is five times stronger than the seals formed with fibrin glues. “We devised a way to compare bond strengths of a commercially available tissue sealant, PhotoSeal™ and super glue – as a benchmark,” Dr Brownlee says. “By bonding together two pieces of amniotic membrane with a surface area about the size of a five cent piece, we found the commercial tissue sealant could only support half a kilogram, while PhotoSeal™ could hold 1.7kg. Superglue was the weakest, supporting only 300 grams.” Long before tissue sealants were developed, surgeons were using sutures to join gaping tissue edges. Sutures work well in the right application, for instance in skin or superficial wounds where the tissue is strong enough to hold a silk or nylon suture. However, not all tissues are created equal. Dr Brownlee explains that when tissue is very soft, such as the dura of the brain, the lining of the bladder, or in the liver and kidneys, sutures alone often cannot give a leak-proof seal because the tissue is not strong enough to support the suture's force. “In these cases, PhotoSeal™ could provide a simple and strong option.” The simplicity of PhotoSeal™ also translates to its ease of storage and transportation. Unlike fibrin-based glues, which must remain frozen prior to use, it is stable at room temperature so avoids the logistical complexities of transporting a frozen sample. Animal models using PhotoSeal™ have had impressive results, showing excellent biocompatibility, Dr Lindall says. “The formulations have been shown to be non-toxic and non-immunogenic, as well as being biodegradable,” he says. Seven weeks after applying PhotoSeal™, animals show no remaining traces of the adhesive agent. Cells that invade the PhotoSeal™ glue have produced new collagen, and the wound is healed to full tissue strength. While commonly sourced from animals, it is possible to use human fibrinogen to make PhotoSeal™. In some cases it can even be made using the patient's own fibrinogen. The research team has also developed a way to replace the fibrinogen as a raw material in PhotoSeal™ which, among other advantages, avoids the risk of exposure to BSE (‘mad cow' disease), as fibrinogen can sometimes be sourced internationally. Now that the PhotoSeal™ prototype is nearing completion, CSIRO is actively looking for investors. “We have spoken to companies in the US and here in Australia . We are also talking to venture capitalists to attract investment for a spin-out company that would develop PhotoSeal™,” Dr Lindall says. “At this stage, it is important for us to consult with surgeons and other medical professionals to find applications that would benefit from the versatility and simplicity of PhotoSeal™, so that we can tailor our technology to these applications,” he says. The group is also considering ways to make the technology applicable to keyhole surgeries, such as endoscopy for cardiovascular applications and arthroscopy for orthopaedic applications. The biocompatibility of PhotoSeal™ with cells during the cross-linking process should mean that it will also be useful in tissue engineering. The fibrin sealant market is estimated to be $400 million in an overall $600 million annual tissue sealant market. While those numbers could suggest tough competition for new sealant products, having three world patents on the photochemical cross-linking technology has given PhotoSeal™ a spot in the ring. “We are currently conducting trials to benchmark PhotoSeal™ against the existing technologies,” Dr Lindall says. “The initial results suggest that PhotoSeal™ will at least find several niche applications, and perhaps a substantial part of the general surgical market too.”APPLICATION A light-activated tissue ‘glue' for sealing wounds BENEFIT Fast setting and stronger than other tissue sealants
For further information contact: |
 IN THIS ISSUE
|
| Home | About Us | eSubscribe | Links | |
|
|
||
|
|
|
Back to main