For the headline writers, the use of stem cells and tissue and bone regeneration within medicine is a dream come true. Science is “to stop age clock at 50”, as the BBC recently put it about a £50m research initiative being launched by Leeds University into developing new medical devices and regenerative therapies.
For medical device manufacturers, however, this new science poses challenges and opportunities. The challenge is whether regenerative medicine could in time make many existing devices obsolete.
The opportunity, on the other hand, is how to embrace and be taken along with this new technology; how firms can evolve their product portfolios and their business models to get the maximum leverage from these advances.
Certainly, according to Kevin Shakesheff, professor of drug delivery and tissue engineering at Nottingham University, device manufacturers should definitely not be seeing regenerative medicine as a threat.
“The device industry still has a huge amount to teach us, particularly in terms of taking innovations through the regulatory process and into the market,” he explains.
“There is a big difference between an exciting breakthrough and a product that is successful or that succeeds in making inroads into a market.”
Shakesheff’s university was one of four (along with Keele, Imperial College London and Southampton) to be awarded £4m in May 2009 by the Biotechnology and Biological Sciences Research Council to work on combining stem cell science and tissue engineering with the development and repair of human skeletal tissue.
The work at Nottingham has focused on the development of polymer materials that can fill the space left by trauma, such as a bone break or the removal of a tumour, to temporarily support the wound and provide a surface for the body’s own stem cells to migrate, in the process encouraging new blood vessels and bone tissue to grow. The aim over the next five years is for the teams to combine forces on skeletal stem cells, scaffolds and materials chemistry and to identify key growth factors, matrix proteins and physical conditions that will enhance tissue regeneration and ultimately lead to more effective skeletal repair strategies.
Key areas of application are likely to include a range of orthopaedic conditions, something of particular importance given the West’s ageing population, treatments for replacing or repairing damaged bones, and patients who cannot spontaneously form bone, such as those who have undergone radiotherapy which has inactivated local stem cell populations.
Leeds University’s Institute of Medical and Biological Engineering unveiled a £50m research initiative in October 2009 with the ambitious aim of giving people “50 active years after 50”.
The research will focus on joints, spine, teeth, heart and circulation, with the aim of developing new technologies for tissue engineering and regeneration, longer-lasting joint replacements and spinal interventions.
Over the first five years, the institute plans to develop at least ten new products and halve the time it takes to get new products to market. Leeds, Nottingham, Keele, Imperial and Southampton are by no means the only academic or medical centres pioneering this approach, with a mass of research activity going on around the world.
Researchers at Tel Aviv University’s Department of Biomedical Engineering, for example, have recently developed an artificial biologically active scaffold made from soluble fibres that, it is hoped, may in time help to replace lost or missing bone.
Similarly, researchers at Columbia University have recently used adult stem cells to create a jaw bone, while new stem cells studies at the University of Maryland Dental School are looking at how high-strength, mouldable and injectable pastes might one day be used to regenerate bone tissue and fill any shape of cavity in a bone defect, broken bone or a wound.
Should device makers be concerned?
“The general concept of regenerative medicine is that it is trying to create therapies for diseases or injuries that do not spontaneously cure themselves,” Shakesheff points out: “For some applications, rather than having a permanent device, you will have a tissue engineering scaffold where, six months down the line, you will just have healthy tissue. In principle, the potential goes across every tissue in the body.” That does not mean this technology is a panacea or that it will always be the best solution for the patient, he is at pains to emphasise.
“A lot of the medical devices out there already do what they do extremely well,” he says. “If you need to pin a broken bone, say, although conventional devices are not ideal they do work well in the sense that the patient is up and walking again on the leg quite quickly.
So physicians have to measure whether a regenerative approach is better than simply using an existing device. It will need to be augmenting existing devices, not replacing them.
“For example, if a major mechanical instability needs to be corrected, such as perhaps a spine or hip implant, then regenerative medicine is not going to offer an instant cure as there has to be a period of maturation beforehand, which will probably not be as acceptable to the patient as having a mechanical support,” he adds.
The regulatory challenge
Back in 2007, a report by consultancy Cap Gemini suggested medical devices companies were likely to be affected in three key ways by the development of regenerative medicine: research and development, regulatory and business development and corporate strategy. On R&D, the challenge would be not simply applying these new technologies but integrating them within their existing R&D processes.
This could mean having to bring in new talent in-house or develop new partnerships, it said. On the regulatory environment, it argued the “classical” separation between medical devices and drugs in Europe and biologics in the US was likely to become blurred as more combination products were developed and brought to market.
“To be able to decide which regulatory path will be addressed, the necessary know-how has to be assembled. The situation is complicated in some cases, especially when using cells, because precise regulatory requirements still need to be defined by the regulatory agencies,” the report said. There might be a requirement for more specialised sales forces, as such products often required more explanation to physicians. There might also be requirement for more business development partnering with biotechnology companies, something that up to now has been more common in Pharma than the medical devices community, Cap Gemini argued.
“Corporate strategy will be affected by these challenges because overall product development times and R&D costs will increase and market launch strategies have to be adapted. As a consequence, risk-adjustment strategies and portfolio management systems have to be adjusted,” it said.
The government perspective
Back in 2006, the US Department of Health and Human Services (DHHS) outlined its vision for regenerative medicine from now until 2020 and it is a vision that, against the backdrop of ongoing concerns about health spending in the US, still has much validity today. Regenerative medicine, the DHHS made clear, not only held out the promise of regenerating damaged tissues and organs in vivo and in stimulating previously irreparable organs into healing themselves, but also had the potential to empower scientists to grow tissues and organs in vitro and safely implant them when the body is unable to be prompted into healing itself.
The technology also had the potential to develop therapies for previously untreatable diseases and conditions, including diabetes, heart disease, renal failure, osteoporosis and spinal cord injuries. In fact virtually any disease resulting from malfunctioning, damaged or failing tissues could be potentially cured through regenerative medicine therapies, said the DHHS.
Beyond the obvious health benefits, regenerative medicine also mapped out a path for the nation against the backdrop of rising health costs, it argued. By 2016, the 56.6 million Americans aged between 55 and 64 in 2006 would join the senior citizen age group. By 2040, as the last baby boomer becomes a senior citizen, the population of senior citizens over the age of 65 in the US would have doubled from what it was in 2006.
By 2040, a quarter of US GDP would be devoted to healthcare. “The majority of these projected costs stem from recurring treatments for diseases that arise from tissue failure commonly seen in the elderly. The baby boomer demographic is one that has seen continual medical advancement in their lifetime,” it argued.
“This group expects the best from healthcare and will have the greatest need for regenerative medicine. Regenerative medicine therapies will help combat common diseases in the elderly such as diabetes, osteoporosis and cardiovascular disease.”
However, to create complex tissues and organs, government resources and co-ordination, as well as private investment and drive, were essential for driving the research effort in an efficient and swift manner. “Regenerative medicine, if driven by a cohesive Federal initiative, has the opportunity to begin producing complex skin, cartilage and bone substitutes in as little as five years,” said the DHHS.
“Tissue and organ patches, designed to help regenerate damaged tissues and organs such as the heart and kidneys are within reach in ten years. Within 20 years, with appropriate Federal funding and direction, the goal of ’tissues on demand’ is realistic.”
Additionally, the world market for replacement organ therapies was in 2006 in excess of $350bn, while the projected US market for regenerative medicine was estimated at $100bn.
“Furthering this field would create jobs and grow a new sector of the healthcare industry while creating a new generation of life-saving products,” the DHHS argued.
Competition or collaboration
There’s probably no getting around the fact that, in some areas, device manufacturers are going to find themselves competing with these techniques, concedes Shakesheff.
“Over the next ten years, tissue engineering concepts will become increasingly interesting as additional devices,” he says. “There will be new concepts available that may, in time, start to replace devices. Cartilage repair, for example, could become much more interventional.” What is also clear is that regenerative medicine will increasingly take its place alongside more conventional interventions and devices, not necessarily instead of, he stresses.
“It will be very much a case of doctors working with devices plus regenerative medicine, rather than having to make decisions around regenerative medicine or devices,” Shakesheff concludes. “Regenerative medicine will fail if it does not have an association with devices.”