The Real Spider-Man

Spiders are remarkable creatures. Perhaps the most impressive thing about them is the silk they weave for their webs. This silk is remarkably strong: it is six times the strength of high-tensile steel, twice as elastic as nylon and more difficult to break than rubber. You could, if you were so inclined, catch a jumbo jet in a web if the threads of that web were as thick as a pencil.

Imagine, then, if that strength could be harnessed in the medical world, perhaps to treat patients in need of bone and cartilage reconstruction. At Oxford Biomaterials, a medical devices company dedicated to the development of silk-based products for tissue repair and regeneration, that is the aim.

Using a biomimetic technology developed and patented by company founders, Professor Fritz Vollrath of the Oxford Silk Group and Dr David Knight of Oxford Biomaterials have developed a biomaterial called Spidrex®, which is modelled on spider silk. Spidrex is manufactured as a tough fibre and a regenerated matrix of the structural silk protein fibroin, as well as a composite of the two.

This variety of forms provides great flexibility in the range of applications which Spidrex can be used for, from complex woven textile-based devices to porous protein sponges. From this, Oxford Biomaterials are pursuing product development in the areas of nerve repair, wound closure, cartilage repair and bone graft materials.

THE STRENGTHS OF SILK

Dr Nick Skaer is CEO of Oxford Biomaterials. He explains that spider silk is so valuable because of its unique characteristics. "It has been a goal of the high-end textile industry for years [to commercially produce spider silk] because of its mechanical properties," he says.

"Spider silk is exceptionally tough and produced at room temperature. What makes it so interesting from our perspective is that it is entirely biocompatible – it has been used through human history as a wound dressing by many different cultures. More scientifically, it has been evaluated by implantation: it does not kick off any inflammatory reactions and it is broken down into its amino acid components reasonably quickly, in about six to 12 weeks.

"That, allied with its great strength, makes it fantastically exciting. Regenerative implants require materials that foster cell growth and encourage tissue regeneration, but that are also slowly degraded by the body so the cells that are growing on them allow the tissue to heal and take the space the implant was occupying.

"A further feature of silks is that they bear a fairly strong homology to human structural proteins such as fibronectin. As such, silks should be something that cells adhere to and grow on very well. It's another reason why they are so interesting from a medical perspective. All the tests we have done have been supportive of this and it looks like an extremely interesting material for our usage."

It was this potential of spider silk that kick started Oxford Biomaterials, Skaer says. "Professor Vollrath and Dr Knight wrote a patent which dealt with how a spider spins silk and how a machine might biomimetically do the same job.

"They also wrote a paper in Nature. Subsequently they were contacted by Technostart [a venture capitalist company] and a company called Spinox [the forerunner to Oxford Biomaterials] was born."

The original goal was to make this biomimetic spinning machine into reality. What Vollrath and Knight had recognised was that the differences between spider silk and silkworm silk are principally created by the way the spider spins it. Skaer explains: "If you were to spin silkworm silk how a spider might spin it, you would have something closer to spider silk.

"We're inspired by spiders but we don't use spider silk per se. It would be a wonderful material to use but the reason nobody does is fundamentally because spiders produce it in minute quantities, whereas silkworms produce it in relatively large quantities – about 1,000 times the quantity of silk per animal. At Oxford Biomaterials, we've developed the original idea of 'spinning like a spider' and are now able to process silk in a variety of proprietary treatments. Silkworm silk is commercially available in huge quantities and through modifying and processing it we have effectively overcome the problem of how to get commercial quantities of spider silk."

BONE REPLACEMENT

One of the products being developed is SilkBone™, an entirely novel biomaterial based on Spidrex which, it is hoped, will address a pressing clinical need for an absorbable but load-bearing bone graft material. SilkBone is a highly porous composite of silk proteins and the natural mineral component of human bone, hydroxyapatite, both of which have already been approved for use in the human body.

This unique material has mechanical properties comparable to human bone, capable of withstanding compressive forces of up to 20MPa, while laboratory tests demonstrate it is likely to be well tolerated in the human body and slowly replaced by regenerating human bone tissue.

"When we started Oxford Biomaterials we sat down and worked out which would be the most appropriate biomedical uses to target," says Skaer. "We did that by considering the properties of the material we had – Spidrex – and which were the great unmet clinical needs that regenerative medicine should be addressing.

"There are a large number of pure mineral calcium phosphate bone substitute materials out there but these lack the tough quality of bone, which is derived from its collagen component. Without the collagen component these materials are brittle and fail catastrophically at comparatively low loads.

"Our approach was to say that in Spidrex we have a structural protein with similarities to collagen that we know cells will grow well on. So why don't we try to develop a material that has the compressive properties of calcium phosphate but also has the structural integrity and cell-adhesive qualities of collagen?

"The SilkBone consortium was born in 2005 specifically to develop a bone substitute material. We have been successful in doing that.

The material required various intrinsic qualities – it needed to be porous, it needed to have a high mineral loading, it needed to be biocompatible, bioabsorbable and to remodel as human bone.

"However, the principle unique selling point we were targeting was that it needed to be tougher than any of the absorbable bone substitute materials currently available. We believe that we have achieved that. SilkBone's key attribute is that it is roughly three times as strong as any of the absorbable bone substitute materials that we know about on the market at the moment. That makes it very exciting."

REPAIR AND RESTORE

Skaer is optimistic about the variety of potential uses for Oxford Biomaterials' products. "The most exciting area for us is moving into cartilage repair," he says. "This is fascinating because it is a massive unsolved problem.

"The bone substitute market is fairly well addressed – they suffer from their mechanical properties but there are solutions including harvested allograft bone. That is not the case with cartilage. It presents probably the most difficult mechanical challenge to any material. Fibrocartilage has to dissipate huge amounts of force generated through running and walking, while articular cartilage has to provide a tough but smooth surface for the articulation of joints.

"Most people subject their knee to about a million cycles every three to six months. Consequently it often gets injured. When cartilage is damaged then the forces it should dissipate are transmitted into the bones and when the cartilage starts to disappear then the bones start to rub together and you get the onset of osteoarthritis.

"A solution to cartilage regeneration is both a massive commercial opportunity and of huge benefit to the population as osteoarthritis often leads to total joint replacement. In Spidrex Cartilage we have a material that is incredibly tough and resilient. It is fundamentally our bone substitute material but without the mineralisation. What we have demonstrated is that these scaffolds have approximately the same compressive strength as cartilage: that is, 40 to 100 times the mechanical properties of other materials that are being developed for cartilage repair at the moment.

"It is incredibly resilient. We can put our Spidrex Cartilage scaffolds into a load cycler and they will regain their shape after each load cycle up to a million times and possibly beyond. This, combined with the excellent biological properties of Spidrex, makes them fantastically well suited to the treatment of cartilage defects."

EXTENDED CAPABILITIES

Oxford Biomaterials creates new companies to pursue each new product's potential. Skaer says: "We think Spidrex has enormous capabilities. We didn't want to get pinned down into developing one or two products when we think it could do justice to an enormous host of different applications. It is hard to get investors to invest in a broad portfolio. To get round this we have "spun out" companies."

To date two companies have been founded. Suturox is to commercialise Oxford Biomaterials" range of Spidrex sutures and take advantage of a market gap and pressing clinical need for a suture that is absorbable but provides long-term support to the healing wound. Neurotex has been established to develop novel silk-based products for a new generation of nerve-repair materials and treatments. A third company, Orthox, is currently seeking funding to take forward orthopaedic technologies including SilkBone and Spidrex Cartilage.

Skaer aims to move from Oxford Biomaterials to take Orthox forward as CEO. "For me, our cartilage and bone technologies represent the greatest opportunity, and having developed the technology from concept, I now want to oversee its translation into commercial devices," he says. "That's why I will be taking the step of leaving Oxford Biomaterials to head up the Orthox team."

The next step for Oxford Biomaterials is to get their products into the marketplace, which will begin happening in the next year. Skaer says: "Our materials are 100% silk fibroin which has been used and successfully implanted in humans for many years.

"Consequently, we expect the regulatory pathway to be relatively straightforward. We similarly hope that everything we see in our experiments to date will be translated into the human environment."

Beyond that, there is potentially a world of opportunity for Spidrex-derived products. Dr Skaer is enormously excited by the possibilities. "If there are [limits to the medical use for our products], we haven't found them yet, but we are very early in our clinical development programme," he says.

"The proof of the pudding is always in clinical trials and we haven't done them yet. It's a long road, but one that we expect to be worth travelling."