The application of bio-printing for the repair and treatment of chondral defects

This proposal seeks to develop methodologies utilising 3D bio-printing for the construction of 3D scaffolds that will facilitate the regeneration of articular cartilage and subchondral bone in patients with cartilage defects. It brings together a new collaborative venture between cartilage biology researchers at Cardiff University and MediPen Ltd, an SME based in Cardiff.
Background to project

Articular cartilage injury is a common disorder of the knee, affecting people of all ages, gender and ethnicity, and with the increase in active lifestyles, the incidence of articular cartilage injury is increasing. If left untreated, isolated cartilage lesions can lead to progressive cartilage loss over time leading to early joint disease such as Osteoarthritis (OA).

Adult articular cartilage is a complex heterogeneous tissue located at the articulating surfaces of bones within a synovial joint. Its presence contributes to protection of the underlying bone, friction free movement and distribution of load bearing within and across the joint. Treatment of articular cartilage aims to restore these properties. Repair of small cartilage defects using tissue engineering approaches such as autologous chondrocyte implantation (ACI) has progressed significantly over the last decade and is now established as a procedure for the treatment of chondral defects to predominantly young patients. These approaches offer the prospect of repairing lost cartilage and at least delay the need for joint replacement surgery, which is the primary medical challenge.

Successful repair of chondral defects is dependent on the reconstruction of a mature articular cartilage and the integration with surrounding cartilage and the underlying subchondral bone. Successful bio-manufacture of cartilage will depend upon the correct combination of cell types (including source), suitable scaffold, ideal microenvironment and mechanical stimulus.
Project aims

This studentship will involve the development of a new modified system where chondral defects can be adequately repaired with a biomimetic that recapitulates the mature cellular and matrix structure of adult articular cartilage. To address this fundamental challenge, we hypothesise that the ex vivo production of biodegradable alginate scaffolds containing cartilage extracellular matrix macromolecules along with autologous cartilage cells (ie stem, progenitor or mature), cultured in the presence of an appropriate mechanical force, can be used as an initial implant for the subsequent regeneration and integration of newly repaired adult articular cartilage in human patients needing ACI treatments.

The PhD studentship will be based at the School of Biosciences and will involve a number of placement visits to MediPen Ltd to develop project-specific objectives involving implementation of 3D bio-printing of the biomimetic composites. Furthermore, the student will be encouraged to utilise the placement opportunities provided by the partner supervisor to develop additional business skills, ie running a SME business and intellectual property protection.

This project will utilise a wide range of laboratory techniques including cell culture, purification of extracellular matrix molecules, molecular and biochemical characterisation of biomimetic scaffolds and mechanical testing which will be carried out using facilities at the School of Biosciences, Cardiff University.
Key deliverables

Bio-printed alginate matrices containing native cartilage macromolecules and chondrocytes that generate viable articular cartilage plugs.
Mechanical pre-conditioning of bio-printed constructs leading to the formation of articular cartilage implants that are morphologically similar to the cellular and matrix organisation found in normal adult articular cartilage.
Efficacy of bio-printed explants in an in vitro model of cartilage repair/regeneration.