Notice

Competition document: regenerative medicine at the front line

Updated 5 April 2018

This Defence and Security Accelerator (Accelerator) themed competition ‘regenerative medicine at the front line’ is seeking proposals for regenerative technologies that can be applied very early after severe, traumatic injury resulting from combat or acts of terrorism. This competition aims to make a real difference by saving lives and reducing disability.

The competition was briefed at the Accelerator Innovation Network event in Bristol on 1 February 2018 .

Phase 1 proposals must be submitted online via the Accelerator Submission Service no later than midday on 11 April 2018.

1. Background

Recent conflicts in Iraq and Afghanistan saw step changes in trauma care which led to great improvements in survival following severe injury from gunshot wounds or blast. However, this has meant that more people survived with life-changing injuries that demanded novel reconstructive approaches and comprehensive programmes of functional rehabilitation.

The nature of future British combat operations could lead to longer casualty evacuation timelines and medical care being delivered in more austere environments. This creates a challenge for the delivery of life-saving interventions and in the ongoing medical management of the casualty not just to survive but to also maximise functional recovery.

Regenerative medicine is one of the UK Government’s 8 great technologies. It holds a good deal of promise for treating people injured as a result of conflict. However, many current approaches can only be delivered at a mature hospital facility in the home nation.

We believe that there are a number of research areas in tissue engineering and regenerative medicine that would be applicable as early interventions could further revolutionise front line trauma care. By shifting the focus of tissue regeneration to earlier in the care pathway, we hope to maximise the success of later functional recovery.

Operational medical care is frequently delivered in internationally-dispersed and austere environments that are challenging for the development and delivery of regenerative medicine technologies. Accordingly, both the mechanism and severity of injury and the environment and logistical context needs to be addressed when considering the use of regenerative technologies early after combat trauma.

These challenges have engendered an increased appetite for risk meaning that Defence has frequently been an early adopter of novel solutions. The outputs of work carried out under this competition will be used by front line military and civilian medical personnel. Patients will tangibly benefit and the burden on later care supplied by both the Ministry of Defence (MOD) and the National Health Service (NHS) will be reduced .

2. Scope

This competition is looking for new technologies and approaches that bring the principles of regenerative medicine to the front line. The competition has 2 technical challenge areas and for both, your proposed technologies must take into account the particular aspects of delivering trauma care in challenging environments. The Allied Joint Publication 4.10(B) gives details on the fundamental principles of medical support to operations.

We’re looking to fund proposals for the experimental development of technologies and approaches that meet the challenges. As a guide, we expect the majority of proposals to focus on low and medium maturity technologies and approaches. We’re not seeking to fund proposals for fully proven products, except where experimental development is required, for example to re-purpose them to meet the specific competition challenges.

3. Competition challenges

3.1 Challenge 1: bioengineered blood components

Haemorrhage is the leading cause of ‘potentially salvageable’ death on the battlefield. Evidence from past and recent conflicts suggests that the use of blood products before reaching hospital, in both civilian and military scenarios, provides benefit. Despite this, it’s still challenging to store and deliver these high value interventions in austere environments.

We think the tools and techniques of tissue engineering and regenerative medicine will likely hold the key to the logistical challenges of using blood products in future conflicts. The production of blood components in vitro, already a burgeoning research area, seeks to remove the requirements for blood donation. With this, and other advancements, comes further potential for innovation. For example, the principles of tissue engineering could be used to produce blood components with reduced immunogenicity, improved storage profiles or augmented functionality. Enhancing or conferring regenerative functions of blood components themselves could also provide a truly disruptive capability for Defence.

In recent combat operations, red cells and platelets have been the only ‘cellular therapy’ used in theatre as replacements for blood lost during haemorrhage. In this challenge, we’re looking for proposals that push at the boundaries of what these high value assets are able to do. That could be in terms of oxygen carriage, storage profile, or multi-functionality. Some examples are highlighted below. This list is by no means exhaustive and we encourage you to bring your own innovative ideas to this challenge:

• platelets could be harnessed and tailored to deliver different endogenous capabilities, including maximising their inherent regenerative functions
• cellular engineering principles could be used to produce an entirely new blood ‘cell’ which exhibits the desired characteristics of other blood components
• blood components could be engineered for improved storage profiles, including temperature stability and shelf life
• blood components could be engineered to possess multiple functionality, including responding to the systemic environment after trauma

3.2 Challenge 2: the preservation and regeneration of soft tissue using biophysical approaches

In this challenge we’re looking for solutions to be used early after wounding following high energy transfer from ballistics and blast to encourage the regeneration of soft tissue and mitigate the ensuing progressive tissue loss. The repair and regeneration of severe tissue damage involves a complex set of biological processes. These processes need to occur with the right balance, at the right time and in the right sequence for a tissue to repair, regenerate and/or undergo successful reconstructive procedures.

Early intervention often leads to more successful outcomes and a variety of biological approaches are under investigation for the manipulation of wound healing and regeneration after significant soft tissue damage (for example the application of growth factors or cellular therapies). Many of these approaches present logistical difficulties at the front line or during casualty evacuation which could be quite protracted in future operations. Extended time to the delivery of definitive care is also likely to negatively impact progressive tissue loss.

Physical approaches can be used to encourage the repair and regeneration of a variety of tissues. These methods are likely to present less of a logistical burden than biological solutions. They may be a useful way to halt the progressive deterioration of tissue during transit and switch tissues to a regenerative trajectory. Proposals are sought that develop the use of acellular approaches for the preservation and regeneration of soft tissues. These should be suitable for use early after wounding (for example in the first 7 days following injury) and may include, for example, the application of materials and/or the use of mechanobiology to alter cellular function (for example cell migration, differentiation or matrix deposition). It’s not necessarily expected that these methods will produce visible regeneration during the timelines associated with treatment in the field and evacuation.

However, you must include clear demonstration of the potential for tissue preservation or the enhancement of subsequent regeneration and reconstruction in your proposed solution. As well as the development of new technologies we’re interested in proposals that could bias current treatment regimen towards regenerative outcomes.

4. What we want

In this Accelerator themed competition we’re looking for proposals that address at least one of the challenges above.

We’re looking for high-risk, high-potential-benefit research proposals that will demonstrate or de-risk the exploitation of technologies. This includes concepts or practical demonstrations (components or sub-systems as well as complete systems), supported by scientific understanding and analysis.

Proposals should be clear on how they apply to military medical care and the potential benefit that they could provide.

Proposals should:

• consider value for money if exploited, including potential costs to MOD of introduction and time-saving benefits
• describe technologies that could be integrated into existing MOD systems and facilities, taking into account training burden and the austere environments in which they will be used
• describe technologies that can be used very early after injury
• provide information on how the technology can be validated or accredited against care standards
• focus on soft tissue
• be innovative and disruptive (in other words a fundamental change compared to established approaches)
• demonstrate the approach at a proof-of-concept level

5. What we don’t want

In this Accelerator themed competition we don’t want proposals for:

• consultancy
• demonstrations of existing ‘off the shelf’ products
• paper-based studies, literature reviews or projects that only offer a written report
• marginal improvements in capability
• technology watch or horizon scanning
• solutions that offer no significant benefit to Defence
• proposals without clear detail on the metrics that will be used to define the success of the solution
• projects that can’t demonstrate feasibility within the timescale
• solutions that can’t be applied to the front line
• purely storage solutions
• improved methods of debridement or other purely surgical procedures

6. Exploitation

The challenges for this competition have been chosen as a direct result of lessons identified from operations in Iraq and Afghanistan and the UK Government’s recognition of regenerative medicine as one of the 8 Great Technologies that will propel the UK to future growth. There is a recognised user need and the Front Line Commands (FLCs) of the Army, Navy and Air Force will be involved throughout the competition. Although this is an extremely challenging area of medical science, the aim of this competition is to support the rapid development of new technologies suitable for use early after combat trauma.

We aim to take forward a number of the most successful outputs from phase 1 projects for phase 2 funding. Only bidders funded at phase 1 qualify for entry into phase 2 of this competition where at least an additional £500,000 of funding will be made available. Phase 2 funding will be awarded, based on the Accelerator assessment criteria, on a per-project basis. As a deliverable of the phase 1 project, successful bidders will also be expected to produce a costed plan of recommended future work.

This competition is being sponsored by the Regenerative Medicine project, within the Protecting Our People programme at Dstl. This programme is one of several that deliver science and technology (S&T) requirements that align with people related Defence strategic objectives and challenges. Exploitation of successful projects is key and will be supported in a number of ways. As part of the Accelerator process, if you’re successfully funded, you will be assigned a Dstl/MOD Technical Partner who will support your project through its lifecycle and help identify relevant exploitation pathways.

The ultimate aim is for regenerative technologies to be taken through clinical trials and support will be given throughout phase 1, phase 2 and beyond to achieve this, as appropriate. This may include, for example, providing end-user specifications, appropriate links for provision of representative samples or patient cohorts, support with other funding applications or further funding through the Dstl research programme. This competition consists of 2 challenges which focus on different areas of regenerative medicine and therefore different exploitation pathways and timescales may be involved.

The exploitation aim is to provide novel technologies in regenerative medicine to the deployed medical environment. The MOD Medical Capability Branch (Med Op Cap) and the procurement agencies will be involved throughout the competition and will identify potential procurement routes should any project gain the relevant level of maturity within the competition time frame.

In addition, the competition will engender new national and international research collaboration, for the benefit of Defence, and interaction with appropriate stakeholders and end users. As such we will be holding a collaboration event during phase 1 and will support the coming together of research partners (as appropriate) throughout the life of the project. Phase 1 projects will be presented at a demonstration event where projects will be given the opportunity to brief members of MOD’s wider user community, international partners, exploitation agencies and wider industry partners.

7. Important Information

Accelerator Innovation Network Event was held on 1 February 2018 in Bristol and a webinar was held on 20 February.

Proposals for funding must be submitted by midday on Wednesday 11 April using the Accelerator Submission Service.

Up to £500,000 is available for phase 1 of this competition. We expect phase 1 proposals for research projects of up to 12 months duration and we anticipate that we’ll fund around 5 to 7 projects in phase 1, with deliverables completed by June 2019.

At least another £500,000 will be made available for phase 2 of the competition. Only those projects funded through phase 1 will qualify for entry into the phase 2 competition.

Read important information about how to submit a proposal to the Accelerator.

It’s important for you to read the Accelerator terms and conditions. For this competition we will be using the Short Form Contract (SFC). This is a MOD initiative that has been designed to ensure Small-to-Medium Enterprises (SMEs), as well as Universities and larger organisations have access to less complex contracting. Proposals will be assessed by subject matter experts from the MOD, front-line military commands and Dstl.

Read about how your proposal is assessed.

All successfully funded projects will be allocated a Dstl Technical Partner who will work with them to develop and refine the proposed approach in order to maximise the exploitation of the output within a military environment. They will provide the interface with MOD, front-line commands and the Dstl stakeholder community and be supported by the Accelerator Innovation Partners.

Deliverables from contracts will be made available to MOD, front-line commands, Dstl technical partners assigned to each proposal and subject to review by relevant government departments.

Full-rights outputs of funded work may be exposed to international government partners. This will only be done under the protection of existing inter-governmental memoranda of understanding.

8. What your proposal must include

Proposals must be submitted via the online Accelerator submission service and include all the information advised within the submission service guidelines.

In addition, specific to this competition, phase 1 proposals must include costed participation:

• at a one-day collaboration event in December 2018
• at a one day demonstration event in June 2019 at the end of phase 1

These events are likely to be held at a Dstl site or in London.

Proposals should include a descriptive scoping for a longer programme (phase 2 onwards) of any duration, but the proposal should be clearly partitioned with a costed proof-of-concept stage, which is the focus of this Accelerator themed competition. Phase 2 work will only be considered after the phase 1 proof-of concept has delivered. The understanding gained in phase 1 will allow Dstl to make an informed decision about funding for future work.

9. Ethical considerations

9.1 Animal testing

All research involving animal testing conducted or sponsored by Dstl is subject to processes that ensure appropriate ethical review and responsible use of animals by Dstl.

We define “involving animal testing” as:

• research that at any stage has involved or will involve use of animals in the United Kingdom, regulated by the Animals (Scientific Procedures) Act 1986
• research that at any stage has involved or will involve use of animals, conducted outside the United Kingdom, regulated by the relevant competent authority that, if in the United Kingdom, would be regulated by the Animals (Scientific Procedures) Act 1986

This requirement for ethical approval isn’t a barrier to funding. If you think your proposal involves animal testing, please ensure that your proposal highlights this. Proposals of suitable technical merit with the potential for exploitation that include animal testing will be required to provide supplementary information to enable appropriate ethical review to take place. Ethical review will be conducted by moderators with suitable expertise who will consider proposals in the context of the Dstl’s Use of Animals policy.

Proposals will be supported through this process. All contracts that involve animal testing will include break points so that projects containing animal testing that can’t obtain the necessary external licensure within the required timescale (for example a licence as required by the Animals (Scientific Procedures) Act 1986 and/or don’t meet the Dstl’s Use of Animals Policy don’t proceed.

9.2 MOD Research Ethics Committee

All research involving human participation conducted or sponsored by any government department is subject to ethical review under procedures outlined in Joint Service Publication 536 ‘Ministry of Defence Policy for Research Involving Human Participants’), irrespective of any separate ethical procedures (for example from Universities or other organisations). This ensures that acceptable ethical standards are met, upheld and recorded, adhering to nationally and internationally accepted principles and guidance.

The following definitions explain the areas of research that require approval:

• clinical: conducting research on a human participant, including (but not limited to) administering substances, taking blood or urine samples, removing biological tissue, radiological investigations or obtaining responses to an imposed stress or experimental situation.
• non-clinical: conducting research to collect data on an identifiable individual’s behavior, either directly or indirectly (such as by questionnaire or observation) All proposals must declare if there are potential ethical issues.

Securing ethical approval through this process can take at least 3 months.

If you think that your phase 1 proposal may require ethical approval, please ensure that you adopt an approach in your submission as follows:

• milestone 1: gaining ethics approval for the project, including delivery of the research protocols (the protocol will need to be detailed by completing the ethics application form)
• milestone 2: proposed research that will be carried out subject to gaining ethics approval (optional phases to be formally invoked, where appropriate)

A contractual break point must be included after milestone 1.

Read more on the MOD Research Ethics Committee.

The requirement for ethical approval isn’t a barrier to funding; proposals are assessed on technical merit and potential for exploitation. Successful proposals will be supported through the ethical review process; however, an outline of your research methods must be included in your proposal to help this process.

10. Dates

1 February 2018	Competition briefing at Innovation Network event
20 February 2018	Webinar 1pm - 2pm
11 April 2018	Competition closes at midday
17 May 2018	Phase 1 funding decision made
Mid-June 2018	Contract placement initiated and feedback provided
December 2018	Phase 1 collaboration/networking event for Phase 1 projects
May-June 2019	Phase 1 demonstration /presentation event
17 June 2019	Final report delivery and Phase 2 proposal deadline
30 July 2019	Phase 2 funding decisions made

11. Queries and help

While you’re preparing your proposals, you can contact us if you have any questions about this competition.

Technical queries should be sent to [email protected] and copied to [email protected].

Queries about the competition process, including commercial and intellectual property aspects, should be sent to [email protected].

Capacity to answer these queries is limited in terms of volume and scope. Your queries should be limited to a few simple questions or, if provided with a short (few paragraphs) description of your proposal, the technical team will provide, without commitment or prejudice, broad yes/no answers. This query facility is not to be used for extensive technical discussions, detailed review of proposals or supporting the iterative development of ideas.

While all reasonable efforts will be made to answer queries, the Accelerator and Dstl reserves the right to impose management controls when higher than average volumes of queries/resource demands restrict fair access to all potential proposal submitters.