Development of a gene activated construct targeting proinflammatory signalling to promote zonal regeneration of osteoarthritic cartilage

Cartilage is a specialised, layered tissue that coats the end of bones, facilitating low friction movement of the joints and providing cushioning from impacts. When cartilage is injured or degenerates, due to diseases such as osteoarthritis, these functions are impaired, causing inflammation, pain and significantly impacting quality of life. No effective treatment is available to repair cartilage or halt the progression of osteoarthritis, with current therapies typically only managing symptoms, until joint replacement surgery is required. Regenerative medicine offers an alternative approach and aims to engineer materials that stimulate tissue repair. However, recreating the specialised, layered composition and weight-bearing function of cartilage, while treating inflammation in damaged joints has proved to be complex. This project aims to overcome these issues by developing a specialised implant that is designed to simultaneously support weight-bearing and treat inflammation to promote cartilage repair. First, an implant will be designed to recreate the three-layer structure and physical properties of cartilage tissue. This will be composed of two integrated materials, a stiff lattice to support weight bearing and a soft gel to support cell repair of the tissue. Next, to enhance the effectiveness of this implant, nanoparticles carrying DNA to instruct cell behaviour will be incorporated into each of the three implant layers. For this, DNA nanoparticles will be developed that program cells to produce small interfering RNA (siRNA) to inhibit inflammation when cells sense inflammation is high and switch-off this siRNA when inflammation returns to healthy levels. These nanoparticles will also program cells to rapidly produce key cartilage molecules to restore natural tissue properties. Finally, this project will test the effectiveness and safety of this nanoparticle-containing implant in a goat animal model of cartilage injury that resembles human cartilage degeneration. This paradigm shifting approach has the potential to revolutionise treatment of degenerative diseases like osteoarthritis.

Award Date
30 June 2022
Award Value
Principal Investigator
Dr Tom Hodgkinson
Host Institution
Royal College of Surgeons in Ireland
Emerging Investigator Awards 2022