Bioresorbable scaffolds for the regeneration of articular cartilage

Articular cartilage is a thin load-bearing connective soft tissue that protects the joints by providing low friction articulating surfaces on the ends of long bones. The cartilage is a highly complex inhomogeneous material whose composition and consequently mechanical properties vary from site to site. Due to its extremely demanding mechanical environment, cartilage is prone to injury or damage. Once damaged/injured, cartilage does not have the ability to heal itself due to the lack of blood supply and may lead to full-thickness defects which ultimately lead to degenerative arthritis (Osteoarthritis, OA). The reduced mobility of the joint due to the degradation of cartilage or OA is a major problem that affects millions of people every year. In the UK alone, nearly one-third of the population (around 8.75 million people) aged 45 and over have OA resulting in the economic burden of around £3.4 billion in indirect costs and £896 million in direct costs to NHS.

The current gold standard treatment for these cartilage defects or OA is total joint replacement, but not without limitations and failures. Alternatively, cartilage tissue engineering (CTE), where the tissue is grown in the lab on biomaterial scaffolds, emerged as a treatment method for cartilage defects. In spite of considerable ongoing and past research, the CTE unable to produce a tissue with required mechanical properties that of native cartilage. These CTE approaches often employ homogeneous scaffold geometries. It is hypothesised that a scaffold with a structural gradient that mimics the native tissue provides a template for superior regeneration of articular cartilage. Additive manufacturing (3D printing) has a significant potential to develop scaffolds with zonally organised micro-architectures and consequently with site-dependent mechanical properties that are similar to native tissue.

Therefore the aim of the current project is to develop zonally stratified cartilage construct similar to that of native tissue by exploiting the tissue engineering capabilities combined with advanced additive manufacturing techniques and novel bioresorbable materials. When implanted the developed construct into cartilage defects, functional cartilage will be regenerated in vivo and thereby it is possible to restore the healthy state of the joint.


Aims and Objectives:

The current project aims to develop a functional cartilage substitute that recapitulates the zonal architecture, biochemical and mechanical properties of native tissue using a combination of bioresorbable materials and 3D printing as well as external mechanical stimulation in a bioreactor system.

To design and develop structurally graded biomaterial scaffolds using 3D printing technologies
To investigate the effects of mechanical stimulation on the tissue formation in cartilage scaffolds in a bioreactor environment
To develop a mechanobiological model to predict the tissue formation in scaffolds due to applied mechanical stimulation

National importance
The proposed research project lies within the Healthcare Technologies (HT) theme of the EPSRC and targets its grand challenges of 1) Developing Future Therapies (the proposal will engineer functional replacement tissues through combined experimental and computational approaches and 2) Frontiers of Physical Intervention (the long-term goal of the proposal is to regenerate and restore the healthy status of the joints through surgical intervention using regenerative medicine and tissue engineering approaches). The proposed project addresses key societal challenges included in the EPSRC Delivery Plan (2019-20), specifically 'Healthy Nation'. Due to the ageing population and rise in obesity in the UK, the osteoarthritis will have a significant future impact on the nation's health and wellbeing and consumes substantial resources. Developing regenerative treatments for joint diseases can be boosted by engineering functional tissue replacements.