Insights into the musculoskeletal disease

The basic science programme is designed to elucidate the developmental cascade of the osteoblast and chondrocyte lineages, both from known precursors and novel sources, and to explore their role in disease. Understanding how local niches impinge on the developmental cascade is a new theme and will provide insight into both the mechanisms underlying disease and the failure for these tissues to normally repair. Ongoing work has provided new insights into the location and form of sclerostin (Hernadez et al 2014) and with the Department of Chemistry we are using nuclear magnetic resonance spectroscopy to investigate chemical signatures within bone matrix and between the matrix and mineral phases of bone, and discovered that poly(ADP ribose) (PAR) plays a role in the mineralisation process itself (Chow et al 2014).

Understanding musculoskeletal repair, regeneration and replacement

Biomaterials and implantable devices are often used to replace or reinstate tissue or organ function lost through disease or injury. Key to the long term success of these approaches is the interaction between host and implanted material. If the biological interface between implant and host doesn’t favour repair then the outcome is poor. Therefore design of new biomaterials that consider cellular responses will improve tissue integration and ensure enhanced functional lifespan of the implant. Cell behaviour on biomaterials is dictated by a combination of absorbed biomolecules and surface topography. Our research uses several different approaches to understand the influence of these factors on cell adhesion, proliferation and differentiation with previous studies identifying how surface topography influences cell:cell communication (Kirmizidis et al 2009) and deposition of a mineralised matrix (Birch et al 2013). Building on these studies, as part of the Arthritis Research UK Tissue Engineering Centre , we are fabricating and evaluating cell response to multi-material composites for use in osteochondral tissue engineering.

In collaboration with the Departments of Materials Science and Engineering we are evaluating the interactions of human cells and in particular mesenchymal stem cells with collagen-based materials for the regeneration of cartilage, meniscus and tendon.

Translating novel interventions and therapy for the clinic

Osteoarthritis (OA) is a significant healthcare burden and preventing or slowing its onset would alleviate considerable patient disability and suffering. One treatment approach is to enhance the surgically induced healing process with biomolecules such as fibroblast growth factor-18 (Barr et al 2014). Alternatively the use of cell therapies offers an exciting opportunity to treat early stage osteochondral lesions that otherwise would go on to initiate osteoarthritic changes. Cells, including stem cells, can be considered a target for treatment (resident) or a part of the therapy. For both strategies, our main approach is to consider cell and stem cell populations in the adult patient. The environment around a stem cell is an important determinant of cell behaviour. We consider ways to influence behaviour mediated by biomaterial fabrication of the environment. Responsible translation incudes clinical trials and currently, we are looking, in a multicentre study, at the role of a cell therapy in avascular necrosis with Bonetherapeutics.