At a glance
- Osteoarthritis (OA) is a debilitating disease affecting more than 528 million people worldwide.
- There are currently no medical therapies to effectively restore the long-term function of OC tissue, forcing many patients to undergo expensive surgery to receive a prosthetic implant, which that often require complex revisions surgeries - a limiting factor especially for younger patients
- To address this challenge, clinicians are exploring alternative therapies based on the concept of Tissue Engineering where cartilage and bone tissues are regenerated rather than simply replaced
- Through the combination of advanced biomaterials, stem cells and bioprinting, Manchester researchers are now developing 3D models of human cartilage and bone.
- This research has the potential to provides the foundations to revolutionise osteoarthritis treatment, creating technology that will be invaluable to study human skeletal development, reduce dependency on animal models and facilitate the safety, efficacy and evaluation of therapies and drugs for the treatment of OA.
Bioprinting_ImagePromo500x298 528 million people are living with problems associated with osteoarthritis (World Health Organisation, 2019).
Despite its prevalence, there is no effective therapy to slow disease progression or regenerate the damaged tissue. In general, patients suffer chronic pain for years without treatment to intervene as the osteoarthritis expands from the cartridge to the bone, before receiving knee replacements when they can no longer walk.
Unfit for purposeWith osteoarthritis most prevalent in people over 60; as our life expectancy grows, so will the percentage of the population suffering. To compound this, available therapies have limited impact. Implants such as prosthetic knee joints eventually require expensive and painful revision surgeries; while less invasive options, such as cell therapy and grafts, fail to regenerate and maintain long-term function of cartilage.
In collaboration with clinicians and cell biologists and using the unique capability of The University of Manchester’s Bioprinting Platform, Dr Marco Domingos is developing new technology-driven regenerative strategies to deliver effective, affordable and long-term therapies, that doesn’t just look to replace the function of the damaged OC tissue but to fully regenerate it.
The vision for a new generation of therapiesThe long-term ambition of our group and others is to deliver a new generation of personalised therapies to effectively restore the function of damaged OC joints and patients’ mobility. Towards this goal we are developing a library of sustainable biopolymers that can be easily tuned to match the biomechanical properties of OC tissues and support the encapsulation of stem cells to create --bioinks--. In the future, we envisage these bioinks being created directly in the clinics using patients- own cells or cell banks and printed into 3D osteochondral surrogates capable of guiding bone and cartilage regeneration. When combine with currently available medical imaging technology, clinicians will be able to bioprint implants that are fully customized to the size and shape of the patients- defect thus improving long-term biomechanical function of the joint. Over time, the biological surrogates will be degraded by the cells and gradually replaced with newly formed tissue.
Driving a fundamental breakthroughThe lack of blood supply and nerves, makes cartilage regeneration extremely challenging. In fact, there are no clinical or Tissue Engineered therapies currently available to fully restore articular joint’s function. In collaboration with other academic groups from Manchester, Dr Domingos is exploring new biofabrication strategies to accurately control the spatiotemporal function and position of stem cells towards the fabrication of a new generation of OC tissue constructs with well-defined but seamlessly integrated bone and cartilage regions.
By tailoring the viscoelasticity and composition of the materials developed in house, his group is already exploring the creation of distinct physicochemical environments to support the encapsulation and stem cell differentiation towards bone or cartilage. These biological materials, also known as bioinks, are then used by his group to print multiple cartilage or bone tissue models, separately, and directly inside tissue culture plates of 6, 12 or 24 wells, with high reproducibility and throughput. In the horizon remains the ambition of developing more physiologically relevant models through the integration of bone and cartilage into a single OC construct. These biomimetic tissue models will allow us to interrogate a multitude of complex mechanisms underpinning cartilage and bone regeneration, paving the way towards the development of new, more affordable and more efficient therapies to treat OC defects.
Using the unique capability of the Bioprinting Technology Platform - based at Henry Royce Institute on The University of Manchester campus - and the potential of bioprinting, he is able to test approaches at scale, to accelerate the transition to clinical trial, reducing the need of human or animal testing.