Articular Cartilage: ageing, hydration and energetics

Secondary Supervisor(s): Dr Anisa Mahomed

University of Registration: University of Birmingham

BBSRC Research Themes: Integrated Understanding of Health (Ageing, Regenerative Biology)

Project Outline

Osteoarthritis is a degenerative disease afflicting articular joints such as at the hip and knee. Over 200,000 knee and total hip arthroplasty procedures take place yearly in the UK alone [1]. During osteoarthritis degeneration of articular cartilage takes place. Articular cartilage is composed of ~70% water by weight, varying through the tissue depth [2]. There is evidence that for articular cartilage, water content may decrease with age [3] but increases before the onset of osteoarthritis [4].

If engineering solutions are to be identified for cartilage replacement, a biomaterial must mimic and integrate with native cartilage, and where necessary subchondral bone, and simulate native structural and functional properties. In addition, its mechanical properties must ensure immediate and durable load bearing and load sharing function. Biomaterials that bear a resemblance to the native organisation of tissues have enormous potential to aid repair/replacement of clinically damaged tissue. Key to cartilage replacement are three-dimensional porous biomaterials that (a) mimic the natural extracellular matrix of tissue, (b) provide the tissue with mechanical support, (c) permit the transport of gases and nutrients, and (d) provoke a minimal immune response. However, a barrier to better replacement materials for articular cartilage is the limited understanding of water structuring in cartilage [5]. However, hydration of cartilage impacts on the energy storage for elastic recoil, and dissipation of energy, during dynamic loading [6].

This research project focus on better characterising the requirements for replacement biomaterials as regards the role, and structuring, of water in the mechanics of articular cartilage. Specifically, the relationship between water structuring, sorption behaviour and resulting surface wettability of cartilage animal models. Further to investigate the association between transport properties and tissue mechanics of cartilage. Animal models for ageing and early onset degeneration will be employed.

Water contained within biomaterials strongly influences their behaviour. Molecular interactions within a biomaterial can result in thermodynamically different classes of water that exists in a continuum. The classes of water and wettability at different levels of hydration of bovine cartilage are to be evaluated. This will provide key data essential to designing a cartilage mimic.

Common characteristics and histological differences between the collagen network and proteoglycan gradient for human, bovine and porcine cartilage are to be exploited. How subtle differences in histological structure alter water structuring, and subsequently the resulting mechanics is to be evaluated. This includes variation of thermodynamical classes of water within native cartilage, and its variation with age and degeneration. Biomaterials, such as hydrogels, best placed to match the thermodynamic and biomechanical properties of cartilage will be explored.

Facilities for mechanical testing are available at the University of Birmingham, while facilities for thermodynamic and water content evaluation are available at Aston University.

References

[1] National Joint, R. National Joint Registry for England, Wales, Northern Ireland and the Isle of Man - 16th Annual Report. 2019.

[2] Venn, Maroudas. Ann Rheum Dis. 1977;36(2):121–9.

[3] Venn. Ann Rheum Dis. 1978;37(2):168–74.

[4] Caplan, Kader. Classic papers in orthopaedics, 2014:161–163.

[5] Cederlund, Aspden. J. R. Soc. Interface 2022;19, 20220364.

[6] Crolla et al. BMC Musculoskelet Disord 2022;23, 228.