Innovation Case Studies

Follow the latest case studies that showcase the diversity of outcomes from our medical device manufacturing research.

To download a printable version of our case studies, visit our downloads page where you can access our latest annual report.

Detail of our approach to research and innovation can be found on our innovation challenges and research page.

Our goal is to advance methods for simulation, design and pre-clinical testing of hip prostheses to address variations in surgical positioning and patient anatomy.

These variations, alongside device design and patient activities, have a significant influence on the function, performance and lifetime of a hip joint replacement. With a revision rate of 30% in the younger, active population, there is a distinct clinical and economic need to deliver improvements.

Our experimental and computational simulation systems are the most advanced in the world. They can be used to control variables during the design, pre-clinical testing and patient delivery stages. They can also be used to predict the effect these variables will have on function and performance, enabling us to increase the precision and reliability of devices – and ultimately improving the long-term outcomes of hip joint replacements for different patient groups.

More specifically, our recent collaborative work with Simulation Solutions includes the development and validation of enhanced hip joint simulation equipment and experimental methods to investigate the effect of differential surgical positioning of components on friction, wear and fatigue of hip prostheses.

Alongside our industry partners, DePuy Synthes and Mathys, we’re applying these advanced methods to both existing prostheses and new designs.

We’ve developed enhanced dynamic computational models that are able to predict the effect of surgical positioning on the contact mechanics and the material stresses and strains of hip prostheses.  We have also delivered a world-first in combining biomechanical, tribological and surgical factors to predict function in pre-clinical simulations.

Our expertise continues to impact on the international community, with MeDe Innovation researchers leading and contributing to the drafting of new international standards for pre-clinical testing of hip prostheses. Our collaboration with Simulation Solutions is now seeing our co-developed simulators being sold around the world.

The next phase of our work see us move towards experimental simulations from a 3D perspective. To date we have used the input of motion and forces on five axes which do not include forces acting at the hip in the anterior/posterior direction. EPSRC’s investment in four new 6-axis hip joint simulators will support this, and research is already underway in collaboration with DePuy Synthes and Simulation Solutions.

Despite the prevalence of joint replacements to treat osteoarthritis in the knee, functional outcomes do not meet the expectations of many patients and well over a third of prostheses need revision in the lifetime of younger, more active patients in their 50s.

These poorer outcomes in terms of function and performance are influenced by the design of the prostheses, but more importantly by the anatomy of the patient and the sheer range of physical activities they expect to be able to regain or maintain.

Current prosthesis designs have been primarily evaluated under a single set of kinematic conditions but, when used clinically, this is clearly at odds with diverse patient populations with a much greater range of kinematic demands and motions.

We are developing enhanced simulation equipment and experimental and computational methods to investigate the effect of different kinematics on the wear and performance of knee prostheses. Not only are we applying these methods to evaluate existing devices, we’re working with industry partners to apply them during the design, pre-clinical testing and patient delivery of new prosthesis designs, enabling us to work towards knee joint replacements that meet patient expectations and last their lifetime.

We’ve produced enhanced dynamic computational simulations to predict the effect of different kinematics on contact mechanics, material stresses
and strains and wear of knee prostheses, leading to the development of new computational wear models. This is the first time that predictive models of the effect of kinematic conditions on contact stress and cross shear on wear have been possible in knee prostheses, and we have validated these
predictions with independent experimental simulations and measurements.

In industry, Biocomposites is using our simulation methods in studies to support new product development and Invibio has adopted our methods
to generate evidence for its product design dossier and to support regulatory approvals of its new PEEK all-polymer knee which is to be rolled out into global clinical trials.

Our long-standing collaboration with Simulation Solutions has led to the manufacture and commercial sale of new electro-mechanical knee simulators to the UK, Europe and Asia.

MeDe Innovation researchers are developing next-generation tissue sparing interventions in the natural knee joint in the form of biological scaffolds and other regenerative therapies.

Intended for use as earlier interventions to treat osteoarthritis and traumatic injuries often caused by sports activity (see theme 1B), these show great promise in helping to avoid full knee replacement surgeries. However, to be fully effective, there’s a clear need to match these interventions to the native properties and function of the individual patient’s knee.

The advent and progress in the development of these tissue sparing interventions has presented new and significant challenges for testing in natural tissue, with pre-clinical simulation of biomechanical and tribological functions being critical to the success of their design, development, manufacture and implantation.

To support this important area of research, we have developed and validated the world’s first experimental natural knee simulation system which can used to pre-clinically evaluate the biomechanical and tribological function of these devices in the natural knee. This is supported by the development of advanced biphasic computational models of the human knee.

This work has included the successful development and evaluation of experimental models for the simulation of ligament constraints and the
development and evaluation of standard operating procedures for evaluating osteochondral grafts.

We have validated the computational models and used these to complete initial studies of the function of allograft and synthetic osteochondral grafts. Although it’s too early to show patient benefits from this research, the methods we’ve developed have been translated for use by industry with simulators co-created with our partner Simulation Solutions that are being sold commercially. We are continuing to advance the simulation system to help realise the potential of innovations in tissue sparing interventions that are being developed by other research groups across the UK.

Injuries to the anterior cruciate ligament (ACL) are a common sporting injury, resulting in loss of stability in the knee.
They account for around 40% of all sports injuries and in the USA over 70,000 ACL reconstructions are performed annually. Most procedures use autograft transplants from a healthy tendon elsewhere in the patient’s body while a smaller number use donor tissue from a deceased donor.

Allografts can reduce operating time and the need to damage another tissue site, but they bring problems with immune rejection and limited availability. Our goal is to develop acellular xenogeneic tendon scaffolds for ACL replacement, providing an off-the shelf product to match surgical and patient needs.

The porcine superflexor tendon was identified as having the appropriate structure and properties for developing a decellularised class III medical device for use in ACL reconstruction. A bioprocess for removing the living cells from the porcine superflexor tendon was developed. This was evaluated over a six month period in sheep, where it showed good functional performance and there was evidence of regeneration.

The know-how from this research was transferred to Tissue Regenix Group Plc who began a clinical trial of OrthoPure XT, a decellularised porcine tendon implant, in 2015 and they remain on track to gain CE marking in Europe.

Our research has continued to examine the effects of variables in the decellularisation process on the biomechanical properties of the resulting scaffolds. This has included looking at the effects of different methods for reducing fat content and bioburden during the bioprocess. Sterilisation with gamma ray irradiation was also found to have some effect on the biomechanical properties of the acellular tendons, but they still retained sufficient strength and flexibility to be used as an ACL replacement. We are also continuing to analyse the cellular mechanisms of regeneration and integration after a graft has been implanted in a joint.

There is still research to be done to determine how we can better match grafts to patients. The ACL can vary greatly between a young female runner, for example, and a young male rugby player. We will explore how varying the age of the pigs the donor tissue is taken from and the bioprocess used to create the acellular implants can better tune ACL replacements to the patient’s body.

The majority of anterior cruciate ligament (ACL) reconstructions are carried out using either bone-patellar tendon-bone (BPTB) or
hamstring tendon autograft. Our research has been aimed at developing off-the shelf acellular allogenic bone-tendon-bone
biological scaffolds for ACL replacement.

We have developed processes for the decellularisation of BPTB grafts from human cadaveric donors. By pretreating the bone and using additional washing, it is possible to decellularise both the hard and soft tissue equally so they can be implanted. Our work allowed us to incorporate approved reagents into the processes, establish microbial monitoring procedures and gain an understanding of how variations in the duration of washes affect the robustness of the process.

These procedures have been transferred to our partners at NHS Blood and Transplant Tissue & Eye Services, who are now working with us to develop a manufacturing process that conforms to Good Manufacturing Practices. When complete, this will allow clinical trials of human BPTB scaffolds for ACL replacement to go ahead and it could provide a new treatment for UK orthopaedic surgeons.

Meanwhile, our work has shown that while additional processing of grafts – such as using acetone to reduce the lipid content and sterilising with gamma irradiation – can reduce the biomechanical properties of the resulting acellular graft, these are still within range of human ACL.

Trials of acellular BPTB scaffolds in sheep have shown excellent functional performance over a six month period along with demonstrating their
regenerative capacity. Evaluation of the cell infiltrate during regeneration is now ongoing.

Further work is underway to evaluate different surgical fixation methods. This will include evaluation in a natural knee joint simulator and virtual models to predict function. Work has also started with NHS Blood and Transplant Tissue & Eye Services to develop a novel chemical sterilisation process for the scaffolds.

Osteoarthritis is the progressive deterioration of articular cartilage, which can lead to severe pain and loss of mobility in sufferers. It is one of the most common joint disorders and is the second cause of disability in the UK. In the USA it is found in 10% of men and 13% of women over the age of 60, accounting for more than 27 million people.

One of the leading causes of early onset osteoarthritis is injury, particularly among younger people who are engaged in sports. Damage to the cartilage, which occurs most often in the knee, is unable to heal and leads to a progressive deterioration. An estimated 10,000 people in the UK suffer knee injuries each year that require cartilage repair surgery. Globally there are more than 2.4 million procedures to repair cartilage
lesions carried out annually. Cartilage allografts are currently rarely performed as the high water content of the tissue means it cannot be easily cryopreserved or frozen, making storage difficult.

To overcome this, our research aims to develop off-the-shelf acellular osteochondral scaffolds that can be implanted to restore cartilage function and
encourage regeneration over time that will, in the long term, either delay or even prevent the onset of osteoarthritis.

Our research has investigated the properties of cartilage from different animal species and joints to find those that are most appropriate for
implantation in the human knee. This identified two potential sources and led us to focus on tissue from young healthy pigs.

In order to get good cartilage replacement, however, our work determined that both bone and cartilage would need to be harvested to produce composite scaffolds. This can help to ensure the graft will fix sufficiently to allow it to integrate.

While acellular porcine bone shows excellent integration into sheep condyles over a 12-week period, the bioprocesses needed to decellularise
osteochondral plugs caused the cartilage to be damaged. To overcome this, a new bioprocess was developed to decellularise whole pig knee joint
condyles while allowing the integrity of the cartilage to be retained. This involved additional washing steps and treatment of the bone component prior to the standard washing process.

Acellular osteochondral grafts produced in this way will be implanted into sheep for 12 months to allow evaluation of these implants. Sterilisation methods will also be evaluated in future work, as will the confluency of grafts in joints. We also have funding to support the translation of the methods and knowledge to human donor tissue for use by the NHS.

Collagen scaffolds are used extensively for tissue regeneration both as a way of maintaining structure and delivering cells for repair. For some uses, however, collagen can degrade too rapidly after implantation to allow adequate repair to take place. Our goal was to develop a novel, multiscale manufacturing platform that would enable the formation of collagen systems with its native triple helix structure still intact, but would allow the stability of the scaffold product to be tuned as desired.

Our process introduces photosensitive organic compounds to the lysine groups on the backbone of atelocollagen in a way that does not denature
the collagen structure. Exposure to ultraviolet or blue light then causes covalent cross-linking between the collagen triple helices, resulting in an increase in the stability of biomaterial. This can be achieved using commercially available ultraviolet lights and is similar to the curing of resin-based dental materials using blue light. This means that the physical stability of the collagen structure can be modified during manufacture and also by surgeons in the clinic.

Our process also allows us to produce a number of clinically useful forms of functionalised atelocollagen, including fibres, filaments, yarns, nonwoven fabrics, films and hydrogels. These can be produced with unusual property combinations not found in natural collagen, including a high degree of swelling without a significant loss of stability. We have been able to produce collagen hydrogels that can swell as much as commercially available hydrogels but have three times the compressive strength, meaning the material is easier to handle. This is an important factor in the clinic.

Among the applications we are developing with our clinical partners is a biomaterial for guided bone regeneration in periodontal surgery. Dental surgeons require bone to secure implants and so need to encourage regeneration in cavities where bone has been lost. Our approach uses collagen to create a membrane that can be placed over the bone cavity to prevent soft tissue from growing into the space, hampering bone regeneration.

Our manufacturing process produces membranes that can last over four weeks, in contrast to commercially-available dental membranes, which
vary greatly in when they fail. We are currently conducting pre-clinical in vivo studies that will pave the way for the first human clinical studies in
collaboration with the Institute of Dentistry at Queen Mary University of London.

Our platform also allows us to produce larger scaffolds that are more suited to wound healing. By creating atelocollagen fibres that can be
assembled into nonwoven fabrics, these can be applied as a wound dressing, helping to manage the moisture levels and so aid healing. These nonwoven fabric assemblies not only combine the stable swelling capacity of our atelocollagen, but the fabric itself is also porous, giving the material a high absorbent capacity while remaining strong enough to be used as a dressing. These dressings have shown accelerated wound healing in vivo in comparison to commercial benchmark products. There are plans for a first-in-human pilot study of this material on digital ulcers in scleroderma patients, in collaboration with Chapel Allerton Hospital in Leeds.
We are in the early stages of producing ‘stem cell bandages’, where collagen-based fabrics can be loaded with stem cells and wrapped around bone
lesions. This can deliver stem cells to the site of a defect to aid regeneration while also providing a physical barrier to keep soft tissue from intruding.
We will also continue research to explore the ability  of atelocollagen materials to control microbial activityand regulate matrix metalloproteinases, which play a key role in wound healing. Further work will also be done in the future on ensuring the long term reliability and consistency of wet spinning of atelocollagen fibres.

One major challenge facing the use of resorbable materials in medical implants is the sudden loss of mechanical properties
while the degraded product is still present, preventing tissue ingrowth. Instead, it is desirable to have controlled degradation so
cells can gradually repopulate an area as the device is resorbed.

Our research has generated phosphate-based glasses where we can tailor the degradation rate by altering their chemical composition. We have
produced phosphate-based glass fibres that have varying resorption rates, which can be bundled together, coextruded with degradable polymers and
then these bundles manufactured into products. This reduces the rapid degradation of the interface between the fibres and the polymer matrix, producing a composite that has mechanical properties that match human bone. Other manufacturing methods include oscillating compression moulding to prevent porosity and improve interfacial strength between the fibres and the matrix. These methods are being used to manufacture prototype resorbable intramedullary nails, which are currently undergoing testing in vitro.

We have also developed a method for enhancing the surfaces of orthopaedic devices by coating them in phosphate-based glass of differing compositions. Using plasma-assisted sputtering, we can produce highly reproducible phosphate-based glass layers with thicknesses of a fraction of a nanometre up to several micrometres. This allows coatings to be applied while preserving the fine topography of an implant. We are currently exploring how to use this technique to introduce coating layers with different properties. Sacrificial layers, for example, can be added to protect the implant during handling before degrading to reveal an osteoconducting layer underneath. Similarly, a thin antibacterial layer can be created to help stop microorganisms forming on the surface of implants, reducing the risk of infection. We are now examining the antimicrobial effect of different glasses and how rapid degradation of a surface layer can prevent bacteria from attaching. Our research is being tracked by DePuy Synthes,
JRI Orthopaedics and Zimmer Biomet.
We have also used an innovative manufacturing process to produce unique porous glass microspheres from phosphate, borate and silicate glasses. These have potential use in multiple applications, including as a bone filler in regenerative medicine. Patients with low bone density could receive an injection of these microspheres together with their own stem cells to encourage the bone to densify. Animal trials are currently underway and work is ongoing with our industry partners, Surgical Dynamics and Ceramisys, to translate this technology further.

Modern hospitals use a variety of different medical imaging technologies and the combination of these with additive manufacturing techniques offers enormous opportunities for the production of highly patient-specific medical devices and surgical tools. The images needed to create
such products, however, need to have a high degree of resolution. We have developed intelligent noise reduction and imaging processing techniques to help generate accurate three dimensional models from medical images. We have also developed analysis and design protocols to ensure
that custom medical devices and tools are manufactured with sufficient accuracy to ensure patient safety.

We have used these technologies to pilot new medical device technologies related to spinal surgery, in collaboration with industry partners. Two of these devices are spinal implants created using additive manufacturing or multi-axis CNC milling. These have been evaluated using a combination of pre-clinical testing and computational modelling to assess the impact the design will have on the device and the loading of the patient’s tissues. Pre-clinical work is to be conducted with the aim of taking these forward to clinical trials.

We have also demonstrated that the technology can be used to produce devices such as drill guides to enhance accuracy in image-guided and robotic
surgery. This offers the potential to enhance patient safety and reduce the time needed to conduct surgery.

The virtual modelling developed for manufacturing medical devices can also be used to help assess the healing process following surgery. Applying the advanced processing and noise reduction techniques to medical images has made it possible to generate 3D models of the trabecular of the spine, even if the medical images are only just sufficient to identify these. This can allow detailed monitoring of the remodelling of bone graft substitutes used in spinal fusion.

Using an MRI-compatible spinal loading device, in combination with MRI imaging sequences and post processing techniques, we have also been able to visualise and quantify the motion of the spine under dynamic loading and assess its deformation.

We also now exploring how the lessons learned from this work in orthopaedics can now be applied to cardiac devices.

Calcium phosphates are well known for their ability to promote bone regeneration in medical implants. Producing them as nanoscale particles is an attractive approach, as this means they can be mixed into a putty or paste that can be injected into a bone defect, allowing repairs to be conducted in a minimally invasive way.

Manufacturing nanoscale calcium phosphates, however, has required complex procedures and is consequently expensive, making this approach prohibitively costly for use in general healthcare settings.

Our research has produced a rapid mix process that can produce medical grade nanoscale hydroxyapatite. Work is now ongoing with our industry partner Ceramisys to scale up this manufacturing process with the aim of producing a commercial product.

We are now also exploring ways to introduce new biofunctionality to these injectable nanoscale calcium phosphates. This research, also conducted
in partnership with Ceramisys, is attempting to enhance the material’s bioactivity to further improve bone regeneration and also to introduce antimicrobial activity.

The risk of bacterial infection in bone following surgery represents a major clinical threat, especially in elderly patients and in immunocompromised
patients. While antibiotics can offer some solution, excessive use of these drugs is undesirable as it can drive antibiotic resistance.

By adding elements to nanoscale calcium phosphates that can suppress pathogens, these innovative materials offer a potential alternative to reducing infection. We have received funding to develop these materials into a new generation of bone graft substitutes for orthopaedic and dental surgery.

The development of 3D printing has offered the ability to produce highly specific and customised structures on demand. For osteochondral surgery, this presents the possibility of creating implants where both the macro and micro porosity can be controlled, allowing them to be tailored to the needs of the patient in the clinic. Using bioactive materials for 3D printing, however, has meant it has been difficult to produce structures with sufficient load
bearing capacity.

We have used the binder jetting 3D printing process, which uses powdered raw material bonded with a polymer, to create novel bioceramic  structures that have load bearing capacity. The composite printed structures are heated in a furnace to burn off the polymer binder and sinter the powder, creating a part that is porous. We have shown that a range of bioceramic materials can be processed, including apatite-wollastonite and silicate glasses.

In a collaboration with the Chinese Academy of Sciences (CAS), we have shown it is possible to process a novel sol-gel synthesised phytic acidderived bioglass, developed at the CAS Institute of Chemistry in Beijing, into scaffolds. This work involved a highly productive exchange of early career researchers between Newcastle University and the research group in China.

The porous scaffolds produced in this way have been shown to have mechanical properties similar to cortical bone. The 3D printing process allows us to create macroscopic channels within the scaffold, which can help to support new bone growth and vascularisation. Tests in vitro have shown the 3D printed scaffolds support the growth of mesenchymal stem cells, while in vivo studies in mice have shown osteoid growth within porous scaffolds.

The next stages of this work will focus on developing devices for specific applications on a large scale with industry partners.

While 3D printing technology offers a potentially powerful way of creating customised implants in the clinic, combining these with cells to allow tissue regeneration is challenging. Printing a single cell is understood, but producing cultures of multiple cells brings problems of agglomeration, where the natural tendency of the cells to adhere to surfaces can cause blockages. To overcome this, we have developed a cell encapsulation process
that allows droplets of media containing single cells to be deposited using an ink-jet printing technique.

Cells are encapsulated in poly-L-lysine (PLL), which creates a temporary electrically charged shell, preventing the bio-ink from coagulating. The shell breaks down and is resorbed within a few hours, restoring normal function to the cells in the printed structure. This approach has allowed us to reliably print cells at rates of up to 1,000 per second. In addition, we have shown that groups of cells can also be deposited through a microvalve printing technique. This research has led us to develop new printhead assemblies, which allow multiple cell types to be dispensed in parallel, allowing the creation of co-cultures. This could eventually lead to the manufacture of entire implants made from multiple cell types in the clinic.

With increased reliability and speed, there is also the potential to produce customised implants that are populated by the patient’s own cells within the timeframe of a single surgical procedure. This would require implants to be turned around in less than an hour to be clinically viable and we are collaborating with clinicians to refine the processes needed to do this. Our research on printing multiple cell types has also opened up new lines of research, where cocultures can be printed for drug testing or disease modelling. We have just received an award, as part of a collaboration led by Alcyomics, from the National Centre for the Replacement, Refinement and Reduction of Animals in Research to print osteoarthritis-on-a-chip for in vitro testing. The “Osteo-chip” will combine several cell  types - osteoblasts, osteoclasts, chondrocytes, synovial cells, immune cells and adipose cells – to mimic the human knee and potentially replace the need for animal models. Osteoarthritis models in animals have limitations and there is a need for more consistent, predictive ways of modelling the disease and testing treatments. This work promises to lead to new collaborations with industry partners.

In the future, we will aim to develop other printed models of cardiac and liver tissue for use in disease modelling and drug testing. We will also continue to develop our printing techniques to produce multicellular microtissues for regenerative medicine.

Producing hydrogels laden with cells offers an attractive way of creating composite structures that have both soft and hard elements. Depositing a gel onto a bone analogue, such as a bioceramic scaffold, provides a cartilage facing modality that can be embedded with cells.

The most common way of bioprinting a hydrogel structure is to use a syringe based system, but these can suffer from slow rates of deposition and, in some cases, poor cell viability after printing. We have developed a jet impingement process that attempts to overcome these issues and enables cells to be rapidly deposited within hydrogels on other biomaterial substrates.

The process directs two jets of gel precursors at one another in mid-air, where they react and form a gel that lands on the substrate. The advantage of this process is that the gel precursors are much easier to process than finished gels. By having the gel-forming reaction at a late stage, it allows printing to be faster and more reliable. We have printed cells in fibrin gels by mixing thrombin and fibrinogen through two impinging jet flows. It has also been possible to print cells in alginate gels by impinging droplet streams of alginic acid sodium salt solution and calcium chloride
solution. We have been able to show that cell-filled gels printed in this way have high viability.

Our work has also led to the manufacture of a multiple jet head that is capable of printing four different materials at once. This provides new levels
of control over the kinds of hydrogel structures that can be produced. By varying the gel formation from point to point, for example, it becomes possible to vary the stiffness of the gel. This could prove useful in a clinical setting where it might be desirable to have a stiffer gel on the outside that is robust enough to survive handling during implantation, while inside the gel may be more liquid to help it bond to the harder bone analogue material.

A patent application has now been filed around the Reactive Jet Impingement technology and the methods for controlling the process. This is the first stage towards commercialisation of this new 3D printing process.

Future work will continue to showcase the full capabilities of the process and its ability to create complex, 3D cell-laden cell structures. We are also
working on integrating our cell printing technique with hard scaffolds for load bearing applications.