Silk is a remarkable material, the full properties of which are still being brought to light. It is everywhere in nature – more than 200,000 different silks are currently known to exist – and at a time of growing concern about ecological damage and depletion of non-renewable resources, demand for silk as a structural material made from renewable resources is growing fast. In the medical field, its use is well-established. Silk scaffolds have been used successfully in wound healing, sutures, and in tissue engineering for bones, cartilage, tendons and ligaments. So what makes it such a versatile material? Principally, its strength. Spider silk, for example, is five times stronger than steel at equivalent weights, and an analysis of the venomous brown recluse spider using an atomic force microscope has shown this is because its strands – each of which is 1,000 times thinner than a human hair – are made of thousands of individual nanostrands 20 millionths of a millimetre in diameter, coiled together like a cable.
Silks are a family of structural proteins that are not only strong, but highly biocompatible, degradable and versatile in their application. They are amenable to aqueous or organic solvent processing, and can be chemically modified to suit a host of biomedical applications. Silk biomaterials are biocompatible when studied in vitro and in vivo, eliciting little or no host-immune response.
“Silk has been used as a suture for centuries,” says Juan Guan of the School of Material Science at Beihang University’s Advanced Innovation Center for Biomedical Engineering. “It has a high specific strength and might be the only micrometre-thin continuous fibre before the invention of synthetic polymer fibres. The protein composition makes silk safe for use in the body, and its combinatorial properties of strength, toughness and resilience make it a strong candidate as a structural biomaterial.”
One name, many materials
Silks come in many different types and from various species, all having specific properties. Spider silk, woven into intricate webs, is familiar to us all, but there is also silkworm silk from the larva of the Bombyx silk moth, which can be farmed in large numbers and create a silk frequently used in textile production.
Then there is silk from bagworm moths, which create a protective case made of silk and other found materials from their environment, such as sand or plant materials. Bagworm silk, particularly from the largest and heaviest Japanese bagworm (Eumeta variegata) could be among the strongest silks investigated to date, though much research still needs to be done into its various mechanical and physical properties.
“Different silks have varied chemical compositions and molecular structure organisations, and most importantly, they are manufactured by different organisms,” explains Guan. “For structural materials to be potentially applied in the medical field, silks are required to have superior mechanical properties, and to be relatively easily obtained in reliable quantity and quality. I chose the two commercial silks produced by Bombyx mori and Antheraea pernyi, for which China is the biggest producer in the world.”
The research project for which Guan chose these silks studied the benefits of mixing silk and synthetic polymers to create materials that could be used to manufacture better biomedical implants. Her work has brought into sight a range of new implantable composites with the best properties of both materials, which could enable the creation of structures that hold bone in place after surgery or replace cartilage cushions in the knee.
“It will take at least ten years for it to be finally approved for use as an implantable device, and only if every stage goes smoothly and delivers promising results.”
Juan Guan
“We have investigated various polymeric materials to composite with silk fibre,” she remarks. “A lot of our earlier work used an epoxy resin thermosetting polymer for its easy processability and mechanical robustness. We currently look at polyester, which is biodegradable in vivo and many of them have been approved by the FDA. Combined with these polymers, the silk composite products would be safe for use in the body.”
Guan, who has been investigating natural silks for more than ten years, is impressed both by how successfully these fibres have helped the survival of the species that produce them and by the immense efforts that have been made to biomimetically produce these silks.
“The natural way of production prototyped by spiders and silkworms is limited when we wish to engineer more complicated shapes and structures,” she says. “The synthetic polymers in silk composites play two roles, an adhesive and a property modifier. I appreciate the invention of silk culture and the value of silk in human culture. Nevertheless, in modern times, the use of natural silks hasn’t been updated to match the need in medicine.”
“I believe the combined material can better suit the requirements of implants for specific tissue engineering,” she continues. “The new silk composite materials and structures will be designed to deliver a combination of sufficient mechanical properties, cell and tissue compatibility and to promote tissue repair and function restoration.”
The development of composite materials with silk is not an entirely new concept, but previous research has typically used short fibres or the primary protein in silk. In contrast, Guan uses silk fabric woven from a single long thread. Silkworm cocoons contain fibres that can reach almost 5,000 feet in length. Such fibres can distribute mechanical stress more effectively than a series of shorter, discrete ones, Guan reports.
“One fundamental attribute of natural silk is its great length to diameter ratio,” she states. “Such a unique property means it can be woven into fabrics 100 microns thin and still retain good strength and other mechanical properties. More importantly, it can be tailor-made to form 3D structures based on extrusion printing techniques.”
The silk and the polymer are combined to form a laminate, which can be cut into custom shapes. Guan proposes that silk composite materials could replace devices based on polycaprolactone (PCL) and polyetherketone (PEEK). She is already working with orthopaedic doctors to create cagelike structures that could replace metal in the process of holding in place vertebrae as they fuse after surgery.
The composite not only has the hardness and rigidity to be compatible with bone, but is also more comfortable than metal structures.
“We are at a stage of in vivo assessment of the material’s cytotoxicity and immune responses using the rat subcutaneous model,” Guan explains. “We are still far from seeing these new silk composite materials being trialled in humans.
The wet environment or the in vivo fluid environment will deteriorate the mechanical properties of composite materials. The biggest concern, I believe, may be the unexpected collapse of the structure due to the fast degradation from the interfacial debonding instead of the surface corrosion from the outside to the inside,” she adds. “The in vivo degradation mechanism will be the focus of our ongoing research.”
A myriad of methods
Guan’s research is just one of many projects that could lead to innovation in medical devices. Among the others is work done by a team at University of Tsukuba, led by Professor Hiromasa Goto, that has created a strong conductive fibre from bagworm silk. The composite fibres act as an optical waveguide and are suitable for use in textile transistors, which could open up numerous applications in wearable medical devices.
Elsewhere, a team of researchers from Tamkang University and National Yang-Ming University in Taiwan is using spider silk to create biocompatible lenses for biological imaging applications. The work involves collecting smooth, uniform dragline silk collected from Pholcus phalangioides spiders, also known as daddy longlegs, and dripping a resin onto the fibres, using the wetting properties of the silk to naturally form a dome shape that can act as an optical lens.
At Tufts University in Massachusetts, Professor of biomedical engineering Fiorenzo Omenetto runs The Silk Lab, which uses silk in a host of applications, among them photonics and optoelectronics, and over the last ten years the lab has pioneered biomaterials-based applications in edible and implantable electronics, wearable sensors, medical devices and therapeutics, biospecimen stabilisation, advanced medical diagnostics and structural components.
Among the lab’s innovations are a bacteria-detecting glove, skin-mounted sensors, and implantable and dissolvable mirrors. The range of potential applications of these multifaceted materials seems to be endless, but Guan points out that the silk road is a long one.
“The development of a new medical product is a concerted effort from scientists in materials science, engineering science and medical science,” she remarks. “For the silk fibre composites, we are currently still investigating the in vivo biological properties using rat and rabbit models.
“It will take at least ten years for it to be finally approved for use as an implantable device, and only if every stage goes smoothly and delivers promising results.” For now, silk will continue to be used in its familiar role of wound treatment, but thanks to the efforts of researchers across the globe, it is now opening the door to a new world of innovation.
