Knees, noses and NASA: how can microgravity help us study and test bioengineered cartilage?
Knee osteoarthritis is a debilitating condition that affects 250 million people worldwide, occurring when the tissues in the knee joint gradually deteriorate, leading to pain, stiffness and reduced mobility. Professor Adetola Adesida from the University of Alberta in Canada is studying this condition using microgravity and developing solutions using the latest bioengineering techniques.
Talk like an orthopaedics researcher
Bioengineering — the application of engineering principles to biology and medicine, often used to create biological tissues or medical devices
Cartilage — the smooth, protective tissue that covers the ends of bones in joints, allowing for easy, pain-free movement
Growth factor — proteins that stimulate cell growth, division and differentiation
Mechanical loading — the process of applying force or weight to a structure, such as the knee joint, which affects how tissues like cartilage develop and function
Mechano-hypoxia — a research method that mimics the combined effects of mechanical loading and low oxygen conditions, similar to the environment inside the knee joint
Microgravity — a condition in which objects appear to be weightless, as experienced in space
Synovial fluid — the lubricating fluid found inside joints that reduces friction and provides nutrients to the cartilage
Imagine if every time you bent your knees – every time you ran, walked, sat, jumped, skipped, squatted and danced – you felt pain. Unfortunately, although we need them for almost everything we do, our knees are not the most reliable of our joints.
Knee osteoarthritis, one of the most common joint disorders, affects more than 250 million people around the world. For many years, it was thought to be caused solely by the ‘wear and tear’ of cartilage. “These days, we describe it as a disorder affecting all of the tissues within the knee including the meniscus, ligaments, cartilage and bone,” explains Professor Adetola Adesida from the University of Alberta. Adetola is studying this disease to learn more about what causes it and how it can be treated.
While the exact cause of knee osteoarthritis remains unclear, several risk factors, which make the disease more likely, have been identified including knee injuries, obesity, ageing, genetics and biological sex. For example, females, especially after menopause, are more likely to develop knee osteoarthritis than males.
Mechanical unloading
Mechanical unloading occurs when we are not using our knees to support our weight – for example when we are lying down, swimming or, if we are lucky enough, when we’re floating in the zero-gravity conditions of space. If our knees are subject to mechanical unloading for too long, the cartilage within them begins to shrink, weaken and waste away. “Because of this, we use mechanical unloading to study the characteristics of knee osteoarthritis,” says Adetola. “Interestingly, studies have shown that when normal weight-bearing resumes, the cartilage can often recover its original size.”
Along with two of his students, Hilda Ma and Madeline Barker, Adetola is using low-gravity conditions to study the effect of mechanical unloading on the knee. They are using a device developed by NASA to test cartilage models, created from human cells, by exposing them to microgravity and observing how this mechanical unloading affects genes and proteins within the cartilage. “Astronauts tend to develop osteoarthritis when they are in zero gravity conditions in space, which causes cartilage loss and joint pain,” explains Madeline. By comparing their results with cartilage under normal gravity, the team aims to understand the mechanisms behind cartilage degeneration in osteoarthritis.
“Another key focus of our research is understanding why females are more prone to, and experience more severe cases of, knee osteoarthritis than males,” says Hilda. “Our goal is to identify the key regulatory molecules and pathways that drive these sex-based differences, hopefully leading to sex-specific treatments and precision medicine approaches.”
Creating cartilage
Adetola and his team use a range of bioengineering techniques to create cartilage models for their experiments. “For example, mesenchymal stem cells (MSCs) have the ability to transform into different types of cells, including osteoblasts (which form bone), chondrocytes (which form cartilage) and adipocytes (which form fat tissue),” says Adetola.
The team collects MSCs from bone marrow, fat tissue and synovial fluid and stimulates them to develop into chondrocytes. “We then seed the MSCs into porous scaffolds where they develop into large tissue structures after several weeks in nutrient and specific growth factor solutions,” explains Adetola. “We have also been using 3D-printing techniques to develop custom-shaped tissues.”
Reference
https://doi.org/10.33424/FUTURUM604
These lab-grown tissues allow Adetola’s team to study knee osteoarthritis at the molecular level, investigate how mechanical forces affect cartilage health and explore how engineered cartilage could eventually be used to replace or repair damaged cartilage, not only in knees but also in other parts of the body. For example, one of Adetola’s other students, Alexander Perry, is investigating how bioengineered cartilage could be used for nasal reconstruction. Some patients with facial skin cancer end up having all or part of their nose removed. “In these situations, the traditional approach to nasal reconstruction requires harvesting cartilage from elsewhere in the body, such as the ears or ribs, to repair the defect,” says Alexander. Unfortunately, these procedures can lead to serious complications such as infections and collapsed lungs. “Our goal is to develop a method of growing nasal cartilage using the patient’s own cells and printing them into a custom shape based on the patient’s anatomy,” continues Alexander.
Testing the tissues
In order to test their lab-grown cartilage models, Adetola and his team use a method called mechano-hypoxia, which mimics the mechanical loading and low-oxygen conditions found inside the knee joint. “The mechano-hypoxia method was developed by a very talented former doctoral student, Alexander Szojka, and is fundamental to our understanding of how bioengineered cartilage will perform in the conditions found in the knee,” says Adetola.
Through their experiments with microgravity, the team has shown that these techniques could also be used to test bioengineered cartilage. “Simulated microgravity and bioengineered cartilage models could be used to discover and test drugs for knee osteoarthritis, potentially helping over a quarter of a billion patients suffering from the disease,” explains Adetola. “Within the next five years, we hope to start clinical trials to evaluate the performance of our bioengineered cartilage in humans, either in reconstructive nasal surgeries or the repair of difficult-to-heal knee cartilage injuries.” By testing their bioengineered tissues in humans, they hope to take significant steps toward transforming the way cartilage damage is treated, offering new possibilities for patients worldwide.
Professor Adetola Adesida
Department of Surgery, University of Alberta, Canada
Fields of research: Orthopaedics, mechanobiology, tissue engineering, stem cell biology
Research project: Investigating potential causes of and treatments for knee osteoarthritis
Funders: Natural Sciences and Engineering Research Council of Canada (NSERC); Canadian Institutes of Health Research (CIHR); Canadian Space Agency
About orthopaedics
Orthopaedics is the branch of medicine focused on the musculoskeletal system, which includes bones, muscles, joints, tendons and ligaments. This system is essential for everything from walking to dancing and playing sports, making orthopaedics critical to maintaining mobility and quality of life. Orthopaedic specialists diagnose, treat and research injuries and diseases that affect movement, such as arthritis, fractures and spinal disorders.
The field is highly collaborative. “One of the many rewards of working in orthopaedics is the joy of working with people from diverse academic backgrounds including clinicians, engineers, biologists, physiotherapists, surgeons and computer scientists,” says Adetola. “There are also many challenges in the field of orthopaedics, but I prefer to see them as opportunities for discovery and innovation. For example, researchers are still debating the exact sequence of biological events that trigger knee osteoarthritis, which makes it hard to find effective treatments or preventative measures. The lack of a reliable animal model that accurately mimics human osteoarthritis also makes it difficult to translate findings from animal studies into human treatments.” Despite these challenges, orthopaedic clinicians and scientists continue to collaborate, sharing research, data and ideas at national and international conferences to move the field forward.
The future of orthopaedics is full of opportunities, particularly with the rapid development of new technologies. “Artificial intelligence (AI) is going to be useful for the next generation of orthopaedic researchers,” says Adetola. “I suspect we will see the application of AI in diagnostics and imaging of musculoskeletal conditions, in biomechanics research where integrating big data is time-consuming, and even in the design of medical devices and robotic surgery.”
Pathway from school to orthopaedics
“I would recommend mathematics, physics, biology, chemistry, computer science, mechanical engineering and medicine,” says Adetola. “These courses will provide some of the fundamental knowledge needed in the different areas of orthopaedics.”
At the University of Alberta, Adetola co-directs the Experiential Learning in Innovation, Technology, and Entrepreneurship (ELITE) Program for Black Youth. This unique programme is designed to create opportunities for Black youth to access hands-on learning and work-integrated training in science, technology, engineering and mathematics (STEM) fields and entrepreneurship.
Depending on your interests, you could follow an academic pathway through university to study medicine or biomedical engineering. However, some careers, such as orthopaedic nursing and orthopaedic technology, may offer vocational or apprenticeship-based routes.
Explore careers in orthopaedics
A career in orthopaedics can give you the chance to help others. “The field of orthopaedics is exciting and open for the discovery of novel solutions to improve the quality of life of all people,” says Adetola. “Orthopaedic-related issues can affect the socioeconomic well-being of a nation, given how it impacts people’s ability to work.”
If you want to learn more about orthopaedics, explore the following organisations, which offer educational resources, careers advice and research opportunities: the Orthopaedic Research Society, the American Academy of Orthopaedic Surgeons, the International Cartilage Regeneration and Joint Preservation Society and the Biomedical Engineering Society.
Meet the team
Adetola Adesida
As a teenager, I was interested in science and playing football. Now, most of my work in orthopaedic research is connected to sports and physical activity. Some of my current work is focused on identifying cell populations that can repair hard-to-heal knee cartilage so that football players and other athletes can return to sports after suffering knee injuries without the risk of developing post-traumatic osteoarthritis.
I love working with students from a diverse background of training. It’s incredible how one problem can be solved from a diverse lens of expertise.
Adetola’s top tip
It might sound like a cliché, but it is important to do what you are passionate and care about
Hilda Ma
Position: Postdoctoral Fellow
Fields of research: Knee osteoarthritis, microgravity
I have always been passionate about sports, many of which place significant stress on the knee joint. When I was 19, I ran a full marathon — while I managed to finish, I ended up bedridden for a week due to a knee injury. That experience made me much more aware of joint health, injury recovery and long-term musculoskeletal damage, sparking my curiosity about this field.
I believe that engaging directly with patients and clinicians is essential. Understanding real-world challenges in patient care will help ensure that my research addresses the most pressing medical needs and contributes to meaningful advancements in treatment options.
Hilda’s top tip
Science is evolving rapidly, especially with advancements in AI, biotechnology and space research. We are at an exciting time where new discoveries are constantly reshaping our understanding of medicine and biology, so explore the unknown, keep an open mind and ask questions.
Alexander Perry
Position: Master’s student
Fields of research: Nasal reconstruction, plastic surgery
My project involves both laboratory work, to further refine the bioprinting method, and the development of virtual surgical models, which guide the design of the cartilage grafts. Ultimately, we hope this research will make nasal reconstruction more efficient and less invasive for patients who need it.
As a hobby, I developed an interest in building and modifying 3D printers and later began learning computer-aided design (CAD) to create my own models. Before joining Adetola’s lab, I worked on a summer project that involved designing custom sleep apnea masks for children with craniofacial malformations. I enjoy learning new skills, and the opportunity to integrate biology with additive manufacturing was a fascinating new area for me.
Alexander’s top tip
Focus on cultivating a strong work ethic and staying self-motivated. Pursuing your own interests makes this easier and more engaging. If you run into challenges along the way, don’t hesitate to reach out for help.
Madeline Barker
Position: Master’s student
Fields of research: Mechanical engineering, knee osteoarthritis
While I’m interested in the day-to-day work I do in the lab, I’m also passionate about the big picture. I’ve always been interested in the space industry, and aware that the health risks are high with space travel. It has been incredible to be part of the work to reduce these risks and satisfying to be able to work on a large-scale project that will also benefit the general population.
It is important to me to be part of the younger generation’s journey in biomedical science and encourage them to pursue opportunities in this exciting field.
Madeline’s top tip
Have confidence in yourself and push through discouragement. I definitely had times when I felt as though I wasn’t cut out for what I was pursuing. I discovered that as long as I worked hard and genuinely cared about my subject, I could succeed.
Do you have a question for Adetola?
Write it in the comments box below and Adetola will get back to you. (Remember, researchers are very busy people, so you may have to wait a few days.)
Learn more about another kind of arthritis called ankylosing spondylitis:
www.futurumcareers.com/improving-treatment-options-for-people-with-ankylosing-spondylitis
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