Ulster University has established a collaboration with leading universities in the USA and Ireland on a £1.5 million research project to revolutionise bone fracture healing in patients across the globe. Brian Meenan talks to OPN about the pioneering project.
Tell us a little about your background and education in the orthopaedic industry?
My academic background is in surface chemistry and its applications to advancing biomaterial science. In particular, my research group at Ulster has been studying the effects of bioactive calcium phosphate materials such as hydroxyapatite (HA) on bone and stem cell biology for over 15 years. It is the application of these systems as potential coatings on implant devices that has been the basis of our interactions with the orthopaedic industry and with clinicians.
Along with my colleagues Adrian Boyd and Patrick Lemoine, we are using physical deposition methods such as radio-frequency magnetron sputter deposition to modify the surfaces of orthopaedic metal alloys in a way that promotes their more rapid integration with bone tissue in vivo. Although such coating techniques are difficult to apply to joint replacement devices such as the femoral stem, they are ideal for providing thin bioactive coatings on pins and wires, where processes such as plasma spraying are less effective due to the need for surface roughening to induce a well-adhered surface layer.
Our recent work on sputter coating from substituted hydroxyapatite materials (i.e. replacing calcium ions in the HA lattice with strontium, zinc, magnesium or silver ions) provides the opportunity to further tune cell response to the implant surface in a way that reflects the maturity and pathology of the contacting tissue, as appropriate.
Could you tell us more about the magnesium-based orthopaedic implants and how they are able to be reabsorbed by the body after a fractured bone has healed?
The overall aim of this US–Ireland R&D centre-to-centre partnership collaboration is to develop bioresorbable orthopaedic implants made from novel high-strength, high-ductility magnesium and magnesium alloy systems that can replace the permanent metals/metal alloys usually used in applications ranging from thin wires to thicker pins, rods and elastic stable intramedullary nails (ESINs), as well as meshes for the treatment of complex bone fractures. We will use both existing high-purity magnesium systems and new magnesium alloys that are currently being developed by the National Science Foundation Engineering Research Centre (NSF-ERC) for Revolutionizing Metallic Biomaterials (RMB) using novel processing methods (patents pending).
In addition to using them in their inherent state, we are employing advanced surface modification and coating procedures developed at the Nanotechnology and Integrated BioEngineering Centre (NIBEC) at Ulster University to control key interfacial properties for the clinical applications concerned; we use bespoke, finite element models developed at the Science Foundation Ireland Centre for Research in Medical Devices (CÚRAM) at the National University of Ireland, Galway (NUIG) to provide the data to target multiple applications by varying bulk and surface properties.
How will your device help surgeons and benefit patients?
A severe bone fracture often requires surgery using metal pins, rods or plates to ensure it heals in the correct position. These implants are most commonly made from stainless steel or titanium and often need to be removed after a fracture has healed.
The novel magnesium-based orthopaedic device being developed by the collaborating universities will encompass the lightweight and durable properties of titanium and stainless steel, along with the ability to be completely reabsorbed into the body. This innovative approach will reduce the need for their subsequent removal, lowering surgical risks to patients and decreasing associated healthcare costs.
Tell us more about the partnership, combining expertise across academia and industry
This exciting partnership represents a unique team of internationally leading academic, clinical and industrial expertise in the fields of material processing, experimental characterisation and computational modelling, with the goal of developing next-generation bioresorbable magnesium alloy systems for the promotion of regenerative biological function in orthopaedic implant devices.
In addition to the project-based objectives, the collaboration also seeks to foster a culture of innovation in bioengineering research and education; providing for entrepreneurship and economic development that will help the USA, Republic of Ireland and Northern Ireland to succeed in a global economy by directly engaging small innovative firms, industries and practitioners and technology transfer officers.
In addition, it will allow graduate students and post-doctoral researchers from RMB, CÚRAM and NIBEC to interact across, both institutional and discipline boundaries in terms of the various research tasks that they undertake.
Who are the other participating universities in Ireland and the USA, and which components of the research are they working on?
The partners involved in the collaboration entitled ‘Bioresorbable magnesium alloy systems for the promotion of regenerative biological function in orthopaedic implant devices’ are: NIBEC at Ulster University (PI Brian Meenan); NSF-ERC for RMB in the USA (PI Jagannathan Sankar); and CÚRAM at NUIG (PI Patrick McGarry).
Will the device only be used in children?
While the development of specialist orthopaedic implant devices for paediatric use is a major focus of this partnership, it is intended that the research will be extended to other areas where the use of magnesium can bring attendant clinical benefits.
In this regard, we will address issues with the long-term invasive nature of current devices, due to their bioresorbable properties under normal physiological conditions, and (importantly) the by-products of resorption are also biocompatible.
Clinically, this feature is highly desirable because it again prevents the need for a second surgery for implant removal, which occurs 20 to 50 per cent of the time among adults and almost always among growing children. Magnesium has the potential to induce mineralisation and bone regeneration, because the (magnesium) ions released by resorption are known to stimulate bone formation by promoting the differentiation of bone-forming cells (osteoblasts), as shown in recent in vivo studies.
While it is recognised that permanent metals are mechanically superior to almost all forms of magnesium and its alloys in regard to their use in the fabrication of weight-bearing orthopaedic implants, they also have a much higher modulus than bone and this can impede healing. Optimal bone healing requires the maturing bone cells to be subjected to physical stresses, such as normal articulating loading and unloading or micro-motions.
When permanent metals support all of the load distribution, stress-shielding of the bone can occur such that in sub-optimal conditions bones can undergo secondary fractures. While a great deal has been done to ensure that stress shielding is minimised by both choice of metal alloy and device design, it still remains a problem.
As magnesium has basic mechanical properties that are much closer to those of bone, its use should then help to prevent stress-shielding.
What stage of development are you currently at?
The collaboration formally launched at the beginning of January 2017 and the various teams are now in place at the partner centres to undertake the integrated work programme.
Preliminary data acquired during the proposal planning phase and proactive support from our clinical and industrial partners has provided us with a specific set of performance targets for the magnesium alloy orthopaedic devices. The collaborating partners from all three jurisdictions will then be responsible for hosting, supervising and training researchers, all of whom will travel to the laboratories of the other partners during the duration of the research programme to carry out key elements of the magnesium orthopaedic device development work.
Are you currently working with any medical device companies?
The work plan is currently supported by inputs from industrial partners OrthoKinetic Technologies, OrthoKinetic Testing Technologies and FWM. Once we have established the required data needed to meet the performance targets for the magnesium alloy orthopaedic devices, as guided by our US clinical partner, we will then engage with the relevant companies in the sector.
What could your product mean for the future of orthopaedics and regenerative medicine?
Ulster University will collaborate with leading universities in the USA and Ireland on a £1.5 million research project to revolutionise bone fracture healing in patients across the globe.
This research has a specific focus on delivering new orthopaedic implant devices for paediatric use, as the need for a second implant removal surgery is almost always required in children as their bones are still growing. This international partnership will see university experts in engineering and healthcare technologies collaborate with industry and clinicians to transform solutions for bone fracture healing.
The partnership has been established so as to foster a culture of innovation in bioengineering research and education, providing opportunities for international research participation for undergraduate and post-doctoral students.
Brian Meenan is the lead researcher from Ulster University’s Nanotechnology and Integrated BioEngineering Centre (NIBEC).
The ERC-RMB is based at the North Carolina Agricultural & Technical State University (NCAT) with partner activities and resources at the universities of Cincinnati and Pittsburgh. ERC-RMB has expertise in materials research, bioengineering, biomaterials, regenerative medicine, smart nanotechnology and engineered systems and test beds, and will lead development and processing of magnesium alloys with input from both CÚRAM and NIBEC.
Based at Ulster University’s Jordanstown campus NIBEC has expertise in medical instrumentation, sensors, diagnostic systems, surface science and biomaterial coating strategies, and will be responsible for the implementation surface engineering and coating of the magnesium alloys for enhanced regenerative biological function, with input from ERC-RMB and CÚRAM.
CÚRAM is based at NUIG and is developing affordable, transformative solutions for a range of chronic diseases, and will provide advanced computational models for the simulation of magnesium alloy orthopaedic device performance under physiological conditions, with input from ERC-RMB and NIBEC.