Regenerative medicine and war: a front-line focus for UK defence

The recent prolonged conflicts in Iraq and Afghanistan saw the advancement of deployed trauma care to a point never before seen in war. The rapid translation of lessons from combat casualty care research, facilitated by an appetite for risk, contributed to year-on-year improvements in care of the injured. These paradigms, however, can only ever halt the progression of damage. Regenerative medicine approaches, in contrast, hold a truly disruptive potential to go beyond the cessation of damage from blast or ballistic trauma, to stimulate its reversal, and to do so from a very early point following injury. The internationally distributed and, in parts austere environments in which operational medical care is delivered provide an almost unique challenge to the development and translation of regenerative medicine technologies. In parallel, however, an inherent appetite for risk means that Defence will always be an early adopter. In focusing our operational priorities for regenerative medicine, the authors conducted a review of the current research landscape in the UK and abroad and sought wide clinical opinion. Our priorities are all applicable very far forward in the patient care pathway, and are focused on three broad and currently under-researched areas, namely: (a) blood, as an engineered tissue; (b) the mechanobiology of deep tissue loss and mechanobiological approaches to regeneration, and; (c) modification of the endogenous response. In focusing on these areas, we hope to engender the development of regenerative solutions for improved functional recovery from injuries sustained in conflict.

 TS=(regenerative medicine OR regenerative therapies OR stem cell development OR tissue engineering) AND CU= (united kingdom OR UK OR england OR scotland OR wales);  TS=(regenerative medicine OR regenerative therapies OR stem cell development OR tissue engineering OR neur* regen* OR restor* tissue) AND CU= (united kingdom OR UK OR england OR scotland OR wales) Resulting publications were then ranked by UK institution to reveal the top 10 institutions for publishing in the regenerative medicine area over the last 5 years. Authors from these publications were also ranked to reveal the top 50 authors (by numbers of publications) publishing in this area.
A subsequent literature review was conducted to help ascertain the level of trauma-related regenerative medicine research compared to other indications (e.g. cancer or neurodegenerative disorders). This review was conducted using the Web of Science (WOS) and MEDLINE databases. The search terms "regenerative medicine," "stem cell therapy," and "tissue engineering" were combined with a range of terms to cover trauma (e.g. trauma*, wound*, burn*) and alternative indications (e.g. neuro*, cancer, diabetes). These searches were not limited to the UK.
Bibliometric analysis was conducted on a combined dataset which comprised of search results extracted from identical searches of WOS and MEDLINE. The references were merged, de-duplicated and cleaned to provide a single set of unique records. Analysis of references by country and author affiliation was undertaken.
These literature reviews found that trauma has not featured highly in the regenerative medicine literature of the last ten years. When the search term "trauma" is combined with "regenerative medicine," "tissue engineering," or "stem cell therapy," it forms around 2% of the overall literature for that search term in each case. This compares to 12% when "neuro" is combined with "regenerative medicine," for example.
Already-collated information on the prevalence of regenerative medicine research by disease indication or organ system is scarce in the published literature itself. The level of trauma-focussed regenerative medicine research was also assessed using the other approaches detailed in these methods, including via other review and strategy documents.
For example, the 2012 UK strategy on regenerative medicine assesses research council funding in regenerative medicine by disease indication and finds particular focus on generic research (e.g. safety, manufacturing) and musculoskeletal, and neurodegenerative disorders. In this review the percentage of regenerative medicine funding directed at "injury" (as defined by UKCRC health category) was less than 1%, only marginally ahead of stroke (including haemorrhagic). By this definition, however, injury and accidents are categorised as fracture, poisoning and burns.
It has been noted by others that funding for injury-related research and overall interest in the development of novel therapeutics in this field lags far behind other public health concerns.
Our findings from this scoping study have led us to the same conclusion; that the volume of regenerative medicine research focussed specifically on severe traumatic injury is small, compared to the scale of the problem.

Other literature:
A variety of reviews into regenerative medicine research have been carried out by the UK Government in the last ten years. The following documents were consulted during our scoping study. In addition Surg. Capt. Prof. Rory Rickard sat as a member of the UK Government's Regenerative Medicine Expert Group (RMEG).

External engagement:
In order to further assess the current research landscape dedicated meetings were held, or this review discussed, with a variety of relevant organisations including, but not limited to, those listed below as well as a variety of individual research groups at a wide range of UK academic institutions.