Engineering better health outcomes

Nanotechnologies promise to shape and revolutionise the future of healthcare worldwide with next generation implants, prosthetics and devices. The Bionic Health 2009 seminar held at The Institution of Engineering and Technology’s (IET) Savoy Place headquarters, in London, proved that there is a growing interest in extending the use of implantable devices for real time diagnosis, remote monitoring and ongoing therapy. Implantable and direct contact electronic devices can support complex tissue functions. Over the last decade or so, advances in sensors and actuators, wireless communications, implantable power sources, biocompatible materials and micro-assembly techniques for 3D and flexible electronic structures have enabled the advancement of intelligent, implantable devices for a variety of therapies. There have also been significant steps forward in remote diagnostics. Since the first Zarlink PillCam video capsule was approved in the US by the FDA in 2001, for example, more than 500,000 patients have safely swallowed one of the devices. In fact, medical reports have found that the accuracy of capsule endoscopy compares very favourably with traditional, invasive methods in diagnosing disorders of the small intestine. In the future, it is hoped that two-way wireless communications with implanted sensors and therapeutic devices will negate the need for patients to visit hospital. Communication with very small implants is already possible, but power consumption is still an issue for long-term implants, according to Henry Higgins of Zarlink Semiconductor. There is no “one size fits all” solution and the communication system, antenna and implant should be designed together, he believes. “Transmission of data to and from an implant is practical and has the ability to make a real difference to the lives of patients,” he commented. Richard Moore, Nanomedicine and LifeSciences Manager at the Institute of Nanotechnology (IoN), has been responsible for work programmes in the areas of nanomedicine and the life sciences since the beginning of 2007. This includes running the NanoMedNet nanomedicine network for clinicians. He also participates on behalf of IoN in EU research projects. Richard Moore argued that medical technology innovation requires an increasingly convergent approach between disciplines such as biological sciences, materials science and information technology. He explained that the basic building blocks of biology operate at the nanoscale. A greater understanding of how living systems work at the nanoscale is therefore leading to better understanding of disease mechanisms and better ways to prevent and treat disease. “Professor Molly Stevens’ work on bone regeneration at Imperial College involves injecting hydrogel underneath the bone coating or periosteum, which causes new bone matter to form on the outside of the old bone,” he explained. “However, we have not yet moved into generating bone or cartilage in vivo. This is still five or more years away. In ten or more years’ time, we may look at engineering partial organs like an artificial pancreas, or manufacturing anti-cancer vaccines. Some cancers may be triggered by a genetic event or malfunction in the body, and it should be possible to vaccinate or introduce molecules into the body that could actually block those kind of events happening.” With degenerative diseases, such as Alzheimer’s and Parkinson’s, he predicted that this is approximately another 20 years away. “You have to first understand their pathological basis – such as what is going wrong biologically and whether it is possible to regenerate some of those tissues,” he continued. “Spinal and nerve tissue is notoriously difficult to regenerate, but people are beginning to find ways to do this. However, you need to create an environment in the body in which it can grow: in other words a scaffold or some support on which neurons can develop. “Again, there is conceptual work on this which could show some promise that we might be able to better understand the mechanisms of these diseases, and provide treatment to help the body regenerate itself where there has been a loss of function.” Richard Moore said that one major problem with brain disease is the need to cross the blood/brain barrier, which presents an obstacle to most drugs that can be used to treat neurological conditions. This barrier blocks larger molecules, and this is an area where nanoscale technology shows promise. Some solutions have also been developed for peripheral nerves. Microsurgery has always struggled to get severed nerves to join up. Richard Moore foresees the possibility of implanting nanoscale materials that allow nerves to grow alongside severed nerves, but the difficulty is compounded a thousand fold at the spinal level. Lizards and other reptiles have a natural ability to regenerate, and understanding how this is done biologically will usher in the ability to biomimetically replicate this process in human limbs.

Bio-inspired scaffolds

Prof. Molly Stevens, research director for biomedical materials at Imperial College, debated the use of bio-inspired scaffolds and novel approaches to tissue engineering, biomimetic nanostructured scaffolds for regenerative medicine and in vivo regeneration of vascularised tissue. Prof. Stevens is a professor of biomedical materials and regenerative medicine and a research director for biomedical material sciences at the Institute of Biomedical Engineering. In 2007 she was awarded the prestigious Conference Science Medal from the Royal Pharmaceutical Society and in 2005 the Philip Leverhulme Prize for Engineering. “Research in regenerative medicine within my group includes the directed differentiation of stem cells, the design of novel bioactive scaffolds and new approaches towards tissue regeneration,” she explained, adding: “We have developed novel approaches to tissue engineering that are likely to prove very powerful in the engineering of large quantities of human mature bone for autologous transplantation as well as other vital organs such as liver and pancreas, which have proven elusive with other approaches. “This has led to moves to commercialise the technology and set-up a clinical trial for bone regeneration in humans. In the field of nanotechnology the group has current research efforts in exploiting specific biomolecular recognition and self-assembly mechanisms to create new dynamic nanomaterials, biosensors and drug delivery systems.” A disagreeable side effect of longer lifespans is the failure of one part of the body – the knees, for example – before the body as a whole is ready to surrender. The search for replacement body parts has fuelled the highly interdisciplinary field of tissue engineering and regenerative medicine. Prof. Stevens described research using directed stem cell differentiation for musculoskeletal engineering and new approaches in tissue regeneration including modulation of cell behaviour through nanoscale architecture and nanocomposite scaffolds. Working with an international team of biomedical engineers, Prof. Stevens has demonstrated, for the first time, that it is possible to grow healthy new bone reliably in one part of the body and use it to repair damaged bone at a different location. Treatment of large defects requires the harvest of fresh living bone from the iliac crest. Harvest of this limited supply of bone is accompanied by extreme pain and morbidity. This has prompted the exploration of other alternatives to generate new bone using traditional principles of tissue engineering, wherein harvested cells are combined with porous scaffolds and stimulated with exogenous mitogens and morphogens in vitro and/or in vivo. Prof. Stevens added: “We now show that large volumes of bone can be engineered in a predictable manner, without the need for cell transplantation and growth factor administration. The crux of the approach lies in the deliberate creation and manipulation of an artificial space (bioreactor) between the tibia and the periosteum, a mesenchymal layer rich in pluripotent cells, in such a way that the body’s healing mechanism is leveraged in the engineering of neotissue. “Using the ‘in vivo bioreactor’ in New Zealand white rabbits, we have engineered bone that is biomechanically identical to native bone. The neobone formation followed predominantly an intramembraneous path, with woven bone matrix subsequently maturing into fully mineralised compact bone exhibiting all of the histological markers and mechanical properties of native bone. “We harvested the bone after six weeks and transplanted it into contralateral tibial defects, resulting in complete integration after six weeks with no apparent morbidity at the donor site. Furthermore, in a proof-of-principle study, we have shown that by inhibiting angiogenesis and promoting a more hypoxic environment within the ‘in vivo bioreactor space,’ cartilage formation can be exclusively promoted.” Prof. Stevens asserted that the new bone actually has comparable strength and mechanical properties to native bone. She concluded: “The potential for using the in vivo bone bioreactor in humans as a means of engineering autologous bone for banking and transplantation is bolstered by our preliminary findings that a confined sub-periosteal space can be created in human tibiae with an elevation of 1 cm between the mesenchymal cambium layer and the underlying bone. “Because the in vivo tissue-engineering approach described enables controlled cellular proliferation, differentiation, and hierarchical organisation within an artificial cavity in the body, it may be useful also in the de novo synthesis of other highly vascularised and multicellular organs such as liver.”