Peek behind the paper: developing callous organoids for ‘living’ implants

In this exclusive interview with Gabriella Nilsson Hall (KU Leuven, Belgium), 3DMedNet takes a closer look at the research behind bioassembled 'living' implants and what is required for these implants to become a clinical reality.

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Gabriella Nilsson Hall

I am Gabriella Nilsson Hall, PhD student at Prometheus – the division of skeletal tissue engineering of KU Leuven (Belgium). My interest in tissue engineering started during my graduate studies at Chalmers University of Technology (Gothenburg, Sweden), where I graduated in bioengineering. After an exchange master thesis at KU Leuven, I started my doctoral research with focus on microtissues for skeletal tissue engineering under supervision of Frank Luyten, Ioannis Papantoniou and Liesbet Geris.    

Could you please tell us about the project covered in the recent 3DMedNet news piece?

The described project was developed by merging developmental biology with an engineering perspective. We looked at how long bones develop in the embryo, where a cartilage intermediate is formed and then transformed into bone, and used this well characterized process as a guideline. Notably, similar events occur during fracture healing when a cartilaginous soft ‘callus’ is formed and remodeled into bone. To avoid diffusion limitations, 100µm sized cellular spheroids were differentiated until a stage where they formed bone microorgans in vivo. When assembled, they fused into larger constructs and were able to heal murine long bone defects, thus acting as a fracture callus. 

With this work, we have developed a process that can be scaled up to an industrial setting, 10 years after the developmental engineering concept emerged.

You can find out more via the full article, 'Developmentally engineered callus organoid bioassemblies exhibit predictive in vivo long bone healing'. 

How do you envision your work benefitting the medical field? What needs to happen before your implants may be available for patients in as few as 4 years? 

We have described a proof-of-concept process for fracture healing using assembled functional building blocks (‘callus organoids’). The next step towards clinical application will require large-scale production of the building blocks to allow formation of cm sized implants, corresponding to human dimensions. An important aspect of the up-scaling will involve automation of the callus organoid production. 

Additionally, although our process focused on fracture healing, we believe that other tissue types can benefit from this building-block approach.  
Developmentally engineered bioassemblies
Figure 1: Developmentally engineered bioassemblies. Provided by Gabriella Nilsson Hall. Available via: 

What challenges have you faced with bio-assembling these ‘living’ implants? 

I would say that the key-word here is ‘living’. 

Since the building-blocks consist of cells and their secreted extracellular matrix, they also behave very different depending on donor cells and microtissue maturation stage. Adaptation of protocols therefore had to be done depending on the conditions. 

What challenges with bio-assembling your implants might bioprinting technologies help to overcome? 

Bioprinting technologies will be of great help for the assembly of callus organoids either by printing only organoids, in combination with biomaterials or for printing structural support. 

Bioprinting would increase precision but also the creation of more complex structures. 

What’s next for you and your research? 

By this time, we have demonstrated the formation of tissues using one type of building-blocks however the benefit of using smaller building-blocks is not only restricted diffusion limitations but also the possibility to design implants’ geometric shapes as well as tissue properties. 

Therefore, the next step will be to assemble building-blocks of different cell types to increase tissue complexity. 

The opinions expressed in this feature are those of the interviewee/author and do not necessarily reflect the views of 3DMedNet or Future Science Group.

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