Regeneration of articular cartilage through biomaterial-controlled partial cell reprogramming to recover youthful cell phenotypes

Cartilage degeneration causes significant pain and decreased quality of life but has no effective treatment. Regenerative medicine aims to engineer materials that stimulate tissue repair. However, this is complex in cartilage due to the specialised, zonal composition and load-bearing function of the tissue. Furthermore, older people are most affected by cartilage degeneration but their cells have a reduced capacity to repair. One driving factors in this reduced capacity is age-related changes to DNA methylation – an epigenetic process capable of altering gene expression. To overcome these issues, this project will develop a scaffold integrating two materials, to support load-bearing but promote cell-mediated repair. For load-bearing, a micro-fibrous scaffold will be fabricated to mimic the different mechanical properties of the deep, intermediate and superficial zones of natural cartilage tissue. This will be combined with corresponding regenerative hydrogels composed of chemically-modified naturally occurring extracellular matrix molecules found in cartilage, to promote rapid cell regeneration and recreate correct zonal cell properties. To enhance the effectiveness of this biomaterial, it will be engineered to contain gene delivery technology that targets and reverses age-related changes in DNA methylation in cartilage cells to restore their youthful, regenerative potential. This project represents an adaptable approach to regenerate joint cartilage, particularly in load-bearing areas of the body. The combination of biomaterials and localised gene delivery targeting age-related cell dysfunction has the potential to significantly alter cartilage degeneration treatment.