Injuries such as burns that involve damage to the dermis rarely heal without formation of a scar. Scar tissue is not identical to the tissue that it replaces and is usually more fibrous and of inferior functional quality. The scar shows an increase in the thickness of the new epithelial layer but the attachment of epidermis is poor making the surface vulnerable to further injury. Sometimes the scarred skin extends beyond the three-dimensional boundary of the original tissue resulting in a raised or hypertrophic scar. Hypertrophic scarring is seen in up to 50% of healed deep burns and this can lead to wound contracture if the scar affects a joint as the skin over the joint is firmer and less extensible and this in turn then limits movement of the joint. Both the contracture and hypertrophic scarring process peak between 3 and 6 months after injury and partially resolve at 12 to 18 months, frequently long after the patient has been discharged.
Restrictive contractures due to serious burn injuries can result in long term aesthetic and physical consequences. Skin contractures bridging or located proximal to a joint lead to joint deformities that severely restrict range of motion (ROM) of the effected joint. Skin contractures are also often accompanied by debilitating levels of chronic pain requiring a high dependency on pain medication. This pain medication can also lead to other undesirable side-effects and unwanted dependency on the drugs administered to control the pain. These factors in isolation or combined can lead to significant disruption in both social and professional life, leading to a marked impact on wounded warrior’s quality of life
Burns account for approximately 10% of all combat casualties (Tina L. Palmieri MD ATAAC St. Pete Beach August 2008) and it has been shown in a study of almost 1000 patients that 38.7% of adult burn survivors admitted to a regional burn center developed at least one contracture and amongst these patients the mean number of contractures was three per patient (Schneider JC et al J. Burn Care Res 2006 pp 508-514).
Post-burn contractures are therefore a very significant problem for the injured war fighter and that any treatment that can alleviate this problem will be of tremendous benefit. Moreover, extensive traumatic skin loss and resulting contractures also occurs with other battlefield injuries that do not necessarily involve thermal burns and is particularly an issue with Improvise Explosive Devices (IEDs)
The current standard of care for a wound contracture involves surgical release or excision of the contracture itself and skin grafting which requires extensive and often repeated surgeries.
Previously, groups both in the UK and US have shown that simple injections of either cultured autologous (from the patient themselves) or cultured allogeneic (from an unrelated donor) human dermal fibroblasts can result in remodelling of the skin and significantly improve the quality the dermis and mobility of the affected joint(s) when injected into burn contractures. Wound contractures that have been present for many years can be improved and softened within weeks. Allogeneic fibroblasts have been shown by many different laboratories not to illicit an immune reaction and they have the distinct advantage over autologous cells in that they can be cultured, banked and tested for things such as viral safety before use and can moreover be provided at point of need in almost unlimited amounts.
As the product is delivered in a series of superficial injections and can be carried out in a doctor’s office, this treatment could represent a new less invasive therapy of choice for patients with burn contractures, where current recourse would be to surgery. This advance could have significant positive benefits to the patient in terms of:• no side-effects of surgery
• treatment given in an out-patient environment without the need for expensive hospitalization
• enhanced quality of life
• lower costs
ICX-RHY has already been used to treat a small number of patients with restrictive contractures and the results led to a collaboration with the McGowan Institute for Regenerative Medicine that is funded by the U.S. Department of Defense to examine this treatment in a Phase I/IIa clinical study.