Your academic and research journey has been marked by a multidisciplinary path combining biology, bioengineering, and in vitro models. Could we revisit the key moments that have shaped your scientific trajectory?
That’s true. My journey has taken me through three faculties of the University of Porto: Sciences, Engineering, and Medicine. Each represented a moment of realisation that my knowledge was insufficient to pursue the research I wanted to develop. My choices were often motivated not by a prior passion, but by the need to better understand certain processes. During my Biochemistry degree, I never imagined moving into Neurosciences; however, during my Master’s in Biomedical Engineering, while studying interactions between bone cells and neurons, I felt the need to deepen my understanding. This led me to apply for a PhD in Neurosciences at the Faculty of Medicine. Later, in order to learn and refine microfabrication techniques and the use of microfluidic platforms, I sought international experience at the University of Southampton with a fellowship from the European Molecular Biology Organization (EMBO). This allowed me to integrate engineering and neuroscience in organ-on-a-chip models. These moments were essential in building an interdisciplinary path and vision that I consider crucial to the work I do today.

You are currently dedicated to uncovering the mechanisms behind bone pain. What challenges persist in this research area, and what recent advances bring us closer to finding more effective solutions?
Bone pain, which is quite common in bone metastases or osteoarthritis, remains one of the most difficult types of pain to treat. Major challenges persist, such as the scarcity of effective and specific drugs. The difficulty lies in understanding, in an integrated way, how different cell types – bone cells, immune cells, tumour cells and, of course, nerve fibres – interact within the bone microenvironment. In recent years, technological advances like transcriptomics and proteomics, combined with artificial intelligence-supported analysis, have made it possible to map the molecular processes involved in these interactions with greater resolution. Alongside this, the development of organ-on-a-chip and 3D models using human cells allows us to test hypotheses in controlled, physiologically and pathologically relevant environments. This combination of tools is revolutionising how we study the mechanisms of bone pain and paving the way for more targeted and personalised therapies.

Your research stands out for the development of organ-on-a-chip models. Could you share with the U.Porto scientific community the potential of these models and how they are particularly useful in studying pain associated with metastases?
Organ-on-a-chip models represent a significant leap forward in biomedical research, enabling the replication of the complexity of living tissues in a dynamic, three-dimensional way. These small devices contain tiny channels through which cells and fluids circulate, simulating the real conditions of human tissue. Within these chips, we can recreate essential tissue functions – such as those of bone – including vascularisation and innervation, allowing us to study diseases far more realistically than with traditional 2D models. In the case of pain associated with bone metastases, these models are particularly valuable, as they allow us to observe how tumour cells affect the function of bone cells and nerve fibres. Additionally, they provide a precise platform for testing new and personalised therapies with greater physiological relevance and without relying heavily on animal models. These systems are transforming how we approach complex diseases and accelerating the development of more effective therapeutic solutions for chronic pain.

In this field of tissue modelling and pain research, there has been a move towards increasingly complex and realistic models. In your opinion, what is the future of this approach and how far can we go in simulating human biology in vitro?
In vitro models are becoming increasingly complex and realistic. They no longer use just a single cell type but integrate various different cells that interact with each other, just as they do in the human body. In the case of bone, it is possible to include mechanical stimuli (such as pressure and tension), which are essential for credibly simulating bone function. Furthermore, we can create compartments within the chip that replicate the structure and organisation of tissues in the body, such as the separation between vascular, bone and neuronal compartments. In my opinion, the greatest advancement is the possibility of using cells harvested from patients, which allows us to test responses to different drugs in a personalised way. These miniaturised models have the potential to predict how a specific patient’s cells will react to a treatment even before it is administered – representing a major step forward in human biology simulation and the development of personalised therapies.

Your work explores fundamental cellular processes, such as cell migration and tissue mechanics. How are these phenomena interconnected, and what can they reveal about broader biological processes, including diseases like cancer?
Cell migration and tissue mechanics are fundamental processes for homeostasis and tissue repair, but they are also deeply connected to disease progression, including cancer and associated bone metastases. Changes in the stiffness of the extracellular matrix directly affect the ability of tumour cells to invade new tissues. In the context of bone, these changes influence both bone remodelling and the interaction with nerve fibres, which are sensitive to mechanical alterations. By investigating how bone cells, tumour cells and nerve fibres respond to mechanical forces and structural changes in the tissue, we can better understand how pathological microenvironments are established and evolve. This knowledge is crucial not only for understanding the metastatic process but also for developing therapeutic strategies that interfere with disease progression at the mechanical and molecular levels.

Your research has strong translational potential, with possible impact on regenerative medicine and tissue engineering. In your opinion, how might new discoveries in your scientific field influence the design of new drugs for treating bone pain?
The advanced in vitro models we are developing – such as metastasis-on-a-chip, inflamed cartilage-on-a-chip and neurovascularised bone-on-a-chip – allow for detailed study of how neurons respond to pathological bone stimuli, like inflammation or the presence of tumour cells. In our research, we aim to decode how cells communicate with each other. It is this knowledge – of new interactions, molecular signals and communication pathways – that can pave the way for developing drugs that differ from current ones. I like to keep this translational goal in mind at all times, even knowing that there is a long path between discovering a new mechanism and creating, validating, or even repurposing an effective drug. The organ-on-a-chip models we develop allow these interactions and hypotheses to be tested precisely, using human cells, and generating data that are more clinically relevant. This approach can accelerate the identification of more effective and less invasive therapeutic strategies for treating bone pain, contributing to a more personalised and patient-centred form of medicine.

Your work has a strong interdisciplinary component and involves national and international collaborations. What role do these partnerships play in advancing your research? Has any collaboration been particularly transformative in your scientific career?
Interdisciplinary collaborations are essential for turning innovative ideas into scientific reality. Working with engineers, biologists, neuroscientists, and clinicians has enabled me to develop sophisticated in vitro systems that incorporate multiple dimensions of the bone microenvironment. In the Flamin-GO project, we are developing a personalised model of rheumatoid arthritis using patient cells, incorporating vascular, bone and cartilage units in an inflammatory context, with the goal of conducting on-chip clinical trials. In the PREMUROSA, BonePainII and BonePainIII projects, I’ve had the opportunity to collaborate with experts in bone diseases and chronic pain from a wide range of scientific and cultural backgrounds. These consortia bring together multidisciplinary teams from several countries, creating an innovative and collaborative research ecosystem. The BonePain initiative, now in its third phase, has evolved from a primary focus on animal models to the development of advanced in vitro models and, more recently, to the integration of clinical samples and patient-centred approaches. This trajectory reflects the consortium’s maturity and its alignment with the demands of modern translational science. These collaborations have been crucial in consolidating my scientific path and contributing to biomedical solutions with real-world impact.

We are living in an era of extraordinary advances in the health and life sciences, driven by new technologies and interdisciplinary approaches. What excites you most about the future of biomedical research? What scientific questions in your field do you believe will be answered in the next decade?
What excites me most is the convergence of technologies such as organ-on-a-chip, bioprinting, gene editing, and artificial intelligence to model and study human biology with precision. I believe that, in the next decade, we will be able to unravel the cellular and molecular mechanisms that regulate nerve sensitisation in the pathological bone microenvironment, and even understand the role of the nervous system in the progression of various tumours. I believe in the growing recognition of on-chip models, not only for their innovative potential but also for their credibility and efficiency in generating physiologically relevant data. Although these models will not completely replace animal use in research, they will allow for a significant reduction. I envision a future, ten years from now, where organ-specific chips are used as clinical decision-making tools, testing treatment responses before they are administered to patients. And twenty years from now, I imagine these integrated systems being routinely used in hospitals – allowing for therapy personalisation, fewer adverse effects, and benefits for all involved in the clinical process. Particularly in my field of research, I believe that within the next decade we will be able to decode how changes in the bone microenvironment specifically modulate pain, paving the way for more targeted and effective therapies with a real impact on patients’ quality of life.

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