Title: NIHR Global Health Research Group on POsT Conflict Trauma; PrOTeCT, Imperial College London
Funder: Department of Health and Social Care

Abstract: We seek to identify the types of injuries that have led to early amputation and are amenable to salvage and to develop and to clinically deploy technology, in partnership with Sri Lanka (SL), for limb salvage and limb regeneration that will be appropriate wherever blast injuries occur. Our research questions are to: identify patient and injury characteristics that have led to early avoidable amputation (WP1); provide immediate surgeon education for limb salvage/amputation using state of the art techniques (WP2); and develop simple, low cost bespoke instruments and implantable devices to maximise the extent of limb salvage (WP3 & 4). INSTITUTION FIT AND SUPPORT Imperial College’s (IC) strategy aims to improve the health of all in society in the UK and worldwide. The Centre for Blast Injury Studies (CBIS, currently funded until 2022), which forms the foundations for this proposal and ensures a sustainable structure for continuity of the proposed Group’s activities, epitomises IC’s ethos of multidisciplinary research excellence, and is uniquely placed to deliver the College’s mission of technological advancement in core engineering disciplines and cross disciplinary engagement to address societal needs in the field of health. IC’s commitment to the biomedical engineering field is evidenced by the Michael Uren Biomedical Engineering Research Hub, a 13-floor development with state-of-the-art laboratory, clinic, and office facilities currently under construction. Imperial recognises the importance of collaboration with external partners and through such global connections believes its excellence and breadth of knowledge can inform key decision makers for the benefit of society. GROWING CAPABILITY Health risks and long term clinical needs are not always addressed or identified in post conflict countries; injury is dealt with rapidly focusing on immediate preservation of life. Universities focus primarily on the education of the young, and research sits low on the list of expenditure. Transitory NGOs identify lessons during their time in these countries, but these lessons can go unlearned by those who stay behind. Growing capability for the benefit of the poorest in SL is embedded at all levels within this proposal. Our key mechanism for achieving this is to create a single research group between the UK, SL, and Lebanon, with engineers, clinicians and scientists from each location working together. Training is included at all levels with courses in the UK, SL, and development of technologies for remote training for advanced surgery. The UoM has recently introduced a biomedical engineering programme and research interest group. This proposal will strengthen this interest group through sharing of expertise, two-way visits and two-way placements, further supporting the development of UoM as a regional centre of excellence in translational biomedical engineering wherein local researchers are enabled to address problems of local interest and relevance. PROGRAMME Our four Work Packages (WP) provide a management structure, a focus on capacity building, education and training, and structured research across the three main locations. WP1 Data, Management, Capacity, Sustainability and Policy (Bull/Burke/Karunaratne/Abu-Sittah/Clasper) We will perform capacity building activities, maintain records, manage communications, run and organise meetings and secondments, provide project and alliance management support, coordinate academic investigators and manage finances and reporting. Under WP1 we will generate data to help create a predictive model for amputation following blast injury. We will utilise key databases available to CBIS through the military. A second dataset will be derived through surveying SL clinicians in order to identify their specific training needs. We will also survey the network of trauma surgeons established across 9 nations affected by landmines, with a specific focus on sharing data with the AUB Medical Centre, the regional centre for blast injuries with the highest caseload internationally. The formal amalgamation and analysis of the data in this work package will serve as evidence for the appropriate assessment of the post conflict status of countries and will be used to inform health care providers and to influence global policy such as demining and land clearance and official development assistance to support effective and targeted intervention by the high-income countries. WP2 Surgical Education and Training (Cobb/Clasper/Hettiaratchy/Abu-Sittah) We will educate and train surgeons for limb salvage/amputation using state of the art techniques that can be easily reproduced in low and low-middle-income countries. The techniques that we have available are reproducible, low cost, and utilise reusable parts. Our three-stage training programme is intended to be transferable to other settings for future use: 1: a surgical team will be brought to the UK to train on cadavers and limb simulants. We have previously developed and run such a course (http://tinyurl.com/h6k84zu); 2: training of surgeons on-site in SL on patients after patient selection and establishment of logistics; and 3: utilisation and development of an augmented reality (AR) training tool, Proximie, to enhance the training initially through telementoring. This will enable the future use of this technology not only for training, but also in surgery. AUB has successfully deployed AR software in providing intra-operative support during reconstructive surgery of blast injuries in Gaza and are currently negotiating its deployment for teams in Syria. IC has used this in arthroplasty. Successful completion of Stage 3 will allow local surgeons to wear Proximie to perform cases whilst surgeons in the UK/Lebanon observe and guide them through the cases. This technology can also be used to assess competency and maintain skills in the long term. WP3 Surgical Planning & Bespoke Reconstruction Technology (Jeffers/Cobb/Bull/Clasper) We will develop technology utilising underlying computer models to virtually reconstruct intact limb geometry from X-rays of the injured limb and the contralateral limb, where available and intact. This will be used to create geometries for fixation devices and surgical cutting guides that work on the principle of maximum tissue salvage and minimum tissue resection that can be made bespoke to the individual injury. The software interface for the surgical planning tool and fixation design will ensure accessibility in remote places for the poorest patients. Surgical guides and fixation devices will be manufactured by selective laser sintering (SLS), a cheap manufacturing method for bespoke devices. The guides will be pinned to the bones in the surgical site and used to guide complex multiplanar cuts required to restore limb alignment, or hold together multiple fragments in a segmented fracture whilst fracture fixation devices are applied. These technologies, with the training provided, will be transferable to other significant musculoskeletal trauma suffered by the poorest, including, road traffic trauma, the leading cause of death and major musculoskeletal trauma for young people aged 15-29 and the second cause of DALYs in the young in LMICs [1]. WP4 Biodegradable Structural Biomaterials (Stevens/Jones/Karunaratne) The need to establish a short term stable interface for healing is balanced against the longer term human and financial cost relating to the possible need to remove fixation devices at a later date. WP4 will design and test biodegradable scaffolds made by SLS or by 3D extrusion printing. The base materials for SLS will be polymers which can be processed into a new hierarchical strut organisation design developed at IC to match trabecular bone strength (patent pending Stevens/Reznikov). This SLS design is currently in pre-clinical evaluation in sheep and we aim to incorporate this technology as part of the fixation devices described in WP3. We will also utilise 3D extrusion printing from hybrids of bioactive glass and biodegradable polymer (e.g. polycaprolactone), which will be osteoconductive and biodegradable, and will also be able to share cyclic loads experienced in meta/diaphyseal defects. 3D printing “Inks” compositions patented by Jones [2] will be made through a sol-gel route and can be incorporated into the reconstructions in WP3 to increase the scope of injuries that can be salvaged. Both scaffolds are ‘near-term’ in translation with the base components having FDA approval for orthopaedic human use. This WP represents the highest risk in the proposal and also offers the highest reward by offering a step change in what injuries could be salvaged in addition to reducing the longer term human and financial liability associated with current interventions. TIMELINES Six Month Targets: recruitment of all staff and students; completion of training needs survey and predictive model of amputation (WP1). Medium-Term Aims & Objectives: deliver a limb salvage/amputation cadaver and surrogate training course in the UK with surgeons from SL and other appropriate countries (WP2); deliver a limb salvage/amputation training course on site in SL with patients (WP2); provide a procedure for geometric planning of subject-specific reconstructions of traumatised limbs of landmine victims to a pre-trauma state using post-trauma data (WP3); develop computational models that quantify loading on tissues for limb salvage and limb reconstruction for preclinical testing of the surgical reconstruction and biomaterials to test their efficacy during loading in activities of daily living (WP3). Long-Term Aims & Objectives: To create biodegradable scaffolds that can regenerate large bone defects (WP4). To provide bespoke instrumentation that enables limb and joint salvage devices to be fixed/deployed with minimal bone removal and maximal tissue salvage (WP3)

Lay abstract: Trauma predominantly affects the young and so accounts for more productive years of work lost than other illnesses. 90% of trauma occurs in Low and Middle Income Countries (LMICs) with a high proportion due to war and conflict. Post-conflict trauma has a large and visible bearing on health outcomes with a high impact on mortality rates, injuries, ill-health, and psychological damage. It is essential that the best health care is provided to trauma patients. Good medical care saves lives, increases functional outcomes, provides independence and enhances quality of life. Landmine explosions are the leading cause of traumatic amputation in Sri Lanka today. Ninety percent of Sri Lanka’s estimated 160,000 amputees lack proper prosthetic limbs and as such are denied a suitable quality of life following injury. Our aim of developing and clinically deploying appropriate technology for limb salvage will change this. Building on our prior work we will seek to develop a thriving research community between the UK, Sri Lanka, and Lebanon, integrating trauma practice, engineering and clinical research. Conflict does not recognise borders and is therefore a global health challenge. The clinical goal for this NIHR Group is limb salvage for victims of conflict trauma. Over the 3 years of the grant, the Group will: • identify patient characteristics that have led to early avoidable amputation; • provide immediate surgeon education for limb salvage/amputation using state of the art techniques; and • co-develop with our partners a biomaterial for bone that can be made locally, based on x rays, and that will resorb over time. This will help us with addressing a number of scientific challenges such as the lack of appropriate surgical skills in Sri Lanka, capacity building and increasing the experience of UK researchers and clinicians in the treatment of civilian blast injuries and their long term issues in LMICs. The Group also seeks to create a single research and translation team with surgeons, engineers and materials scientists co-located in Sri Lanka, Lebanon and the UK. Importantly, it is also hoped that the grant will help strengthen the Biomedical Engineering programme at the University of Moratuwa to include a Trauma stream. Ultimately, the Group will be able to access rare data and experiences to allow an improved understanding of civilian blast injury where global terror remains a threat to civilian populations and this will help us better understand the healthcare burden post conflict to influence and enable overseas intervention.

Research activity codes: 5.4 SURGERY;6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: INJURIES AND ACCIDENTS