Solving cartilage regeneration: not as simple as it seemed

Articular cartilage plays a pivotal role in our mobility, acting as a cushion between our joints and enabling smooth movement. However, its lack of blood supply makes healing from injuries a significant challenge, often leading to long-term pain and reduced mobility for those affected. Traditional treatments fall short, as they lack the mechanical strength to withstand continuous movement. Florencia Abinzano spent her PhD developing a regenerative solution for cartilage damage and received her doctorate on March 11th for her work on cartilage implants. 

Not as simple as it seems

Florencia fell in love with cartilage tissue when working on her master’s thesis. She remembers: ‘When researchers first started with tissue engineering, everyone thought cartilage would be an easy tissue to recreate as it has no nerves or blood vessels. However, many years later, we are still not able to fabricate cartilage tissue, but I hope this thesis work is a small step towards a durable solution.’   

The unique challenge in cartilage tissue engineering lies in the harsh biomechanical environment and the small number of resident cells called chondrocytes, combined with the hypoxic conditions limiting cell growth. Thus, the first vital steps in this work were finding the right cell type, growth factors and a suitable delivery material to withstand these harsh conditions.  

Finding the right cell type

A complicated challenge to solve was finding the right cell type. The current gold standard for cartilage regeneration treatment uses autologous chondrocytes. Florencia: ’Chondrocytes are obtained from a healthy area of the patient's cartilage, which creates more damage in the process and only yields very few cells. When trying to multiply them in the lab, they lose their phenotype and stop producing the correct extracellular molecules that make up native cartilage tissue.’   

In the quest for a more suitable cell type, Florencia and her research team explored articular cartilage-derived progenitor cells (ACPCs). In contrast to chondrocytes, they reside mainly at the surface of cartilage and can multiply to clinically relevant numbers. Florencia: ‘Even if they make up a small percentage of total cartilage cells, they can be easily isolated and multiplied into large numbers without losing the ability to make the right molecules.’   

The next step was finding the best growth factor to support these cells. Florencia: ’We found that the growth factor BMP-9 could jump-start them into becoming more mature and producing cartilage-like matrix.’  

3D printed mesh has advantages over hydrogels

The following step involved designing a delivery system that could withstand the harsh conditions of cartilage and support the growth of the ACPCs. After testing a variety of hydrogels, they group found that the ideal system was not a hydrogel, but a 3D printed mesh created by melt-electro writing. In contrast to a hydrogel, this scaffold provides mechanical strength, and cells are in direct contact with each other which stimulates their growth.  

The resulting cartilage implant was tested using equine cells in vitro and in an animal study.  In the animal study, the implant was paired with a bone anchor which failed, compromising the evaluation of the implant. This highlighted the necessity of thorough testing in realistic settings before implanting in vivo.  

Fortunately, the in vitro results from human cells were also promising, confirming the potential of ACPCs to become the new gold standard in cartilage repair,  and might one day offer a solution to millions of cartilage patients worldwide.  

The journey to the dissertation

The journey to finishing her dissertation was a long and unusual route. Florencia:’ Between a pandemic and having 2 little boys, the timelines for my PhD were quite different. In the end, I finished writing my dissertation in my free time while already working as a post-doc for the last two years.’   

Working at TU Eindhoven, Florencia is pursuing her passion in mentoring and teaching future cartilage researchers. Florencia: ‘I believe in the progress I have made and hope that even if I don’t manage to develop a treatment for cartilage repair, one of my students might!’  

This article was written by Francesca Pileri.