AMBER Scientist receives funding for regenerating a native-like collagen architecture in the body to repair injured soft tissues

13 January 2025

Research utilising bioprinting will prevent joint damage and occurrence of Osteoarthritis

Scientists regenerating a native-like collagen architecture in the body to repair injured soft tissues

AMBER Researcher Professor Daniel Kelly of Trinity College Dublin has been awarded funding for project micro2MACRO (m2M) a BioEngineering research project which will utilise bioprinting and regenerate a native-like collagen architecture in the body to repair injured soft tissues and limit the occurrence of joint damage and osteoarthritis.

The project led by Professor Kelly has been awarded by the European Union under the Horizon Europe Programme and includes research partners in seven other countries including the Netherlands, Germany, Austria, Finland, Portugal, New Zealand, and Switzerland.

Effecting up to 15% of the population by the time they reach the age of 60, joint damage and subsequent osteoarthritis (OA) is a painful and mobility limiting condition. It is a leading cause of disability and more frequent cause of activity limitation than heart disease, cancer, or diabetes. Due to the lack of a truly regenerative solution and the aging population, the number of joint replacement surgeries is expected to increase within the next 10 years by more than 30%, to 1.5 million procedures per year in the UK, Germany, France, and Italy alone, with an estimated burden on the healthcare system of €75 billion.

Coordinator of the Project, AMBER Researcher Professor Daniel Kelly said: ‘Due to its increasing prevalence, the economic burden of osteoarthritis-related care will continue to rise, putting additional pressure on already burdened healthcare systems. Current approaches to repair damaged joints only temporarily resolve symptoms and are not apt for long-term relief, the regeneration of the joint or the prevention of OA. This funding will allow us to research methods of bioprinting to mimic the body’s own architecture and repair injured soft tissues which in turn will reduce the pain associated with and prevalence of osteoarthritis’.

Current cartilage regenerative therapies only induce the formation of a temporary (fibro)cartilaginous tissue that does not possess the same architecture and mechanical characteristics as the original native cartilage. As the new tissue is relatively low in type II collagen and lacks the typical arcade fiber organisation, it is much weaker and only provides limited mechanical resilience. This inevitably leads to mechanical failure and problems for the patient in the longer term.

Although the proper reestablishment of this collagen network would result in mechanically stable cartilage, the collagen turnover is low, hence complete tissue restoration in vivo is particularly challenging. Therefore, new cartilage tissue engineering strategies need to not only consider the short-term development of cartilage-like grafts in vitro but should also guide the regenerative process in vivo for long term restoration.

In past attempts addressing this challenge, m2M partners have incorporated degradable biomaterial fibers into bioprinted cartilaginous auricular and articular grafts to bolster their mechanical properties. Although this approach initially improved the overall strength of the tissue constructs, it failed to address the long-term issue of tissue durability, as the collagen network was not restored when these fibers degrade.

Regenerating a native-like collagen architecture is central to the durable repair of most injured soft tissues (e.g., meniscus, intervertebral disc, ligament, tendon, arterial tissue). It is evident that relying solely on conventional bioprinting strategies to mimic the shape and bulk mechanics of such tissues will not surmount these obstacles nor yield a genuinely regenerative solution. Moreover, the environment that these bioprinted tissues experience in vivo in is often highly inflammatory and additional challenges arise when trying to engineer grafts for treating larger defects; these include matching the specific size and shape of the joint defect and ensuring a sufficient supply of nutrients and oxygen throughout the graft.

In m2M it is envisioned that innovative developments in bioprinting technologies can aid in overcoming these hurdles. The m2M project aims to address this challenge by using bioprinted cells with guiding structures to direct tissue self-organization both in vitro and in vivo. m2M will develop a new bioprinting platform capable of spatially patterning microtissues into scaled-up, personalised durable load-bearing grafts and guiding their (re)modelling into fully functional tissues in vivo within damaged or diseased environments.