The complex biology behind successful regeneration
Dr. Berta Cillero-Pastor, principal Investigator at teh MERLN Institute for Technology-Inspired Regenerative Medicine at Maastricht University
“We need to look beyond cartilage and understand the joint as a whole.”
Why is it still so difficult to regenerate cartilage or bone, despite decades of research? According to Dr. Berta Cillero-Pastor, part of the answer lies in the complexity of the biological environment. A biomaterial does not interact with just one type of tissue or cell. Once implanted, it becomes part of an environment in which different tissues, cell types, immune responses and mechanical forces all interact.
Cillero-Pastor is Principal Investigator at the MERLN Institute for Technology-Inspired Regenerative Medicine at Maastricht University. Her research focuses on spatial omics and advanced analytical technologies to understand how cells respond to biomaterials and treatments.
During the latest Great Small Talk Show, we spoke with her about cartilage and bone regeneration, personalised medicine and what is needed to bring regenerative therapies closer to the clinic.
Cartilage regeneration has been studied for decades. Why is it still so difficult?
“One of the problems is that many potential solutions focus specifically on regenerating cartilage as an isolated tissue.
But when you look at a joint, many other things are happening. You have the synovial membrane, Hoffa’s fat pad and other tissues interacting with each other. When you introduce a new biomaterial, you are not putting it into a neutral environment. The joint may be inflamed, cytokines are being produced and the mechanical load may not be properly balanced.
So instead of looking only at cartilage, we need to understand the joint as a whole and the interactions between the different tissues.”
Does that also mean there may not be one solution that works for everyone?
“Exactly. My group focuses strongly on personalised medicine, and I don’t believe there will be one single solution that heals every patient in the same way.
There are different types of defects and very different patients. Someone may have metabolic syndrome or obesity, while another patient may be a young, high-level athlete. All these factors can influence whether an implant succeeds.
So we need to look not only at the tissue, but also at the patient as a whole.”
How can spatial omics help us understand that complexity?
“Spatial omics allows us to study biological molecules while preserving information about where they are located within a tissue. In simple terms, it shows us not only what is happening, but also where it is happening and which cells are involved.
In our laboratory, we develop analytical technologies, particularly using mass spectrometry, to study how different cells respond to treatments and biomaterials. We don’t just want to measure the overall response. Ideally, we want to understand what happens at the single-cell level.
When you implant a biomaterial, many different cell types become involved. In bone, for example, you have osteoblasts and osteoclasts, but also cells of the immune system. Understanding cell-specific responses is crucial if we want to identify which biomaterials are the best candidates.”
You also work with companies. What does that collaboration bring?
“Companies often have their own specific expertise. In our laboratory, we try to bring different technologies and disciplines together.
For example, we develop new in-vitro models for diseases such as osteoarthritis. We collaborate with companies developing mass spectrometry technologies, but also with companies working on organ-on-chip technology to create better models of the joint environment.
By bringing researchers, clinicians and companies together, you can identify the right applications and understand where the real gaps are. That exchange works both ways.”
One example is your work on cartilage-on-a-chip. What are you trying to achieve?
“We want to model the joint, but not simply by creating one standard cartilage-on-a-chip model.
Our role is to characterise the molecular fingerprints of different patient groups, for example patients with or without metabolic syndrome, or patients whose cartilage damage is related to trauma.
We believe these different patients populations may require different models to properly understand the disease and ultimately find the right treatments.”
With bone implants, a lot of attention goes to mechanical properties. Are we paying enough attention to biology?
“That is changing. We increasingly realise that we need to understand how different cell types respond to the surface and chemistry of an implant.
In one of our projects (DARTBAC), for example, we investigate how cells and bacteria respond to biomaterial surfaces. Specifically we focused on studying how macrophages and bacteria react differently to variations in the surface topography of titanium.
So instead of only asking whether an implant integrates well with bone, we also need to understand what happens to immune cells and bacteria. Modelling that entire environment is extremely difficult, but I believe it is the only way to eventually find the right implant for each patient.”
Does this complexity sometimes clash with the way companies develop products?
“For companies, it is important to develop a product and move it through the different phases of quality control and production. Scientists may look much more at the biological complexity behind it.
That is why public-private partnerships are so valuable. Companies can learn from biology experts, while researchers can learn from companies about what is actually needed to translate a technology into a product.”
What is needed to take these technologies towards clinical application?
“Automation and standardisation are key. It may not sound appealing, and as scientists we are not always enthusiastic about spending a lot of time on it. Developing a new method may seem more exciting.
But if you really want to move towards clinical application, you have to demonstrate that a method is robust, reproducible and scalable.”
From complexity to clinical application
For Cillero-Pastor, developing better regenerative therapies starts with understanding what really happens when a biomaterial enters the body. That means looking beyond the damaged cartilage or bone, studying the responses of different cell types and recognising that the biological environment can differ considerably from one patient to another.
Spatial omics provides increasingly powerful tools to uncover those differences at single cell resolution. But understanding them is only part of the journey. To support clinical development, these technologies also need to become robust, standardised and reproducible.
It may be less spectacular than discovering a new biomaterial, but it could prove just as important in bringing regenerative therapies from the laboratory to the patient.
Rethinking Bone and Cartilage Repair
Bone and cartilage are closely connected, yet repairing them presents very different challenges. Progress depends not on a single breakthrough, but on bringing together a better understanding of damaged tissue, new regenerative technologies and clinical experience.
In this series of three interviews, we explore bone and cartilage repair from three different perspectives: research, clinical practice and innovation. Together, they show where the field stands today, what is holding progress back and what it may take to bring new solutions closer to patients.
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