Matthew Carson – PhD student, Queens University Belfast

In 1997 a pioneering study showed that bone formation could be stimulated in humans solely through injections of powdered nacre, or mother of pearl, derived from the shells of oysters. The findings of this work were exceptional but cannot be fully appreciated without first understanding the scale of bone related disorders.

Fractures, whilst an obvious choice when thinking of bone damage, tend to heal within 2 months of injury. Massive trauma can result in complex fractures which are more difficult to treat, whilst a small number of normal fractures can show delayed healing. Osteoporosis on the other hand is poorly understood but more prevalent and difficult to treat. This disease causes a decrease in bone mass and a breakdown in structure, making bones weaker and more likely to fracture after even mild impacts and falls. People in their fourth or fifth decade of life are most at risk of developing osteoporosis; particularly postmenopausal women, of which 30% are estimated by the World Health Organization to have the condition. From a sufferer’s perspective, the disease can be extremely painful, limit movement and significantly reduce quality of life. It’s also expensive, with osteoporosis related fracture treatment costing UK health services £5.4 billion to treat in 2010 and £37.4 billion for Europe as a whole. This condition alone highlights the need for effective clinical interventions for bone disorders, yet there are many others not expanded upon here, such as osteopetrosis and Paget’s disease of bone.

So what can be done clinically to address these complications? There are three key factors that need to be considered when attempting tissue regeneration for the treatment of musculoskeletal disorders. These include a scaffold for tissue growth to take place upon, a cellular component to carry out tissue formation and the inclusion of bioactive factors. Bioactive factors refer to any substance which is able to produce a biological response in the body of the host. In the field of tissue regeneration this is focused upon those factors able to increase the action of the cellular component and therefore decrease healing times and improve patient outcomes. Specifically for bone regeneration Bone Morphogenetic Proteins, or BMPs, are the most clinically developed example of a bioactive. These proteins are known to stimulate bone formation, with both BMP-2 and BMP-7 available for clinical application in the US and UK. Both are being more frequently used in treatment, though their success is highly variable between individuals, gender, age groups and the type of bone being treated. As such there is a need for more effective bioactives to stimulate healing.

One highly promising reserve of novel bioactives is the ocean, which contains a huge variety of organisms adapted to survive under a range of different environmental conditions. Returning to the example of nacre from oyster shells, this shiny material is mostly comprised of a type of calcium carbonate, as well as a small organic component containing proteins important to the process of shell mineralisation. This composition is similar to that of human bone, which led Atlan and his team to the hypothesis that its inclusion in sites of damage may promote healing. Powdered nacre was mixed with the blood of eight middle-aged female patients before being injected into upper jaw defects. Bone biopsies, taken after six months, showed that nacre was non-toxic, presented good biodissolution and enhanced mineralisation. These results indicate the potential of marine extracts to promote healing in relatively simple procedures which require minimal processing steps.

Whilst nacre sparked the interest of the scientific community it is by no means the only marine extract which shows clinical potential. Many algaes have been shown to contain extracts able to promote the activity of bone forming cells, particularly brown macroalgaes. Mineralising species such as the red algae L. coralloides are also thought to increase mineralisation, and there is even a company devoted to selling a ground version of the algae for human consumption. In fact the organisms so far tested solely for their impact on bone cells and tissues are fairly diverse, including corals, sea cucumbers, many molluscs and bacteria, amongst others. However, considering the great diversity of invertebrate life within the oceans, these examples represent only a fraction of the total species which could be tested.

Overall, many marine extracts tested to date do show real promise for the stimulation of bone healing. However, our understanding of these processes is still limited, specifically as to what molecules actually stimulate cell activity and the mechanism of these effects. Furthermore, the majority of research has so far focused on determining the response of cells and little effort has been made to test their impact in animal injury models. Until these steps are taken the clinical use of many extracts will remain limited. However, research in this area continues apace, and the real question now is not whether marine extracts are feasible for use, but how long until they are common place in a clinical setting?