MB ChB MRCS CClinEd
RN BSc PhD
Professorial Unit of Surgery
University Hospital of North Tees
David J Leaper
MD ChM FRCS FACS
Department of Wound Healing
European Tissue Repair Society
The repair of soft connective tissue (eg, skin, muscle) begins with several cascades and overlapping phases of coagulation and collagen/platelet interactions, followed by various cellular activities involving inflammation and angiogenesis (preparation phase), the appearance of fibroblasts and finally the formation of scar tissue (maturation phase). In hard connective tissue (eg, bone) the repair is commenced with the formation of mineralised cartilage matrix, later replaced by woven and lamellar bone, which is finally remodelled to increase the strength of the repair. In specialised tissue (eg, liver), the repair process involves specific physiological activities at cellular level, which can result in tissue regeneration.
In the clinical environment, the process of tissue repair is most commonly seen during the recovery phase following traumatic injury or surgery. The methods and the time taken for repair vary with different tissue types. However, factors such as wound infection and poor nutritional status can have detrimental effects, prolonging and interfering with the repair process. A prolonged repair process can delay patient mobilisation and increase the length of hospital stay. Wound infection, while delaying the healing process, also increases the overall cost of care. A pan-European review suggests that the cost to its healthcare systems associated with surgical site infections alone may be as high as €19.1bn per annum.(1) Antibiotic treatment for wound infection may cause adverse effects and can increase the likelihood of resistance. Therefore the importance of optimising the process of tissue repair, without infection, to improve clinical outcomes and cost-effectiveness cannot be overemphasised. This paper gives a short overview of just a few of the exciting developments taking place.
Innovative clinical applications
Warming The negative impact of perioperative hypothermia on patient care is well documented. Patient warming, which is traditionally used to avoid or to treat hypothermia, has now been shown to provide further clinical gains, such as reducing the rate of wound infection and shortening hospitalisation.(2,3) It has been demonstrated that warming can influence the local tissue environment by improving blood flow and increasing oxygen tension.(4) A clinical study demonstrated that the oxygen availability to the wound tissue might be an important factor in predicting wound infection.(5) Warming either locally (eg, wound warming) or systemically (eg, whole body warming) can be considered as an innovative way to provide optimal conditions for the process of tissue repair. The two types of systemic warming, which are becoming the most popular, can be undertaken using forced warm air or the more flexible conductive carbon polymer mattress.
Wound dressings There are a growing number of wound dressings, ranging from simple to complex, passive and interactive. They can vary in terms of their type of material, constituents (such as antimicrobials or growth-stimulating factors) and character (such as simple or sustained release of antimicrobials). For example, the role of silver in wound care has been recognised for a long time, and various clinical trials involving several different silver dressing presentations have been published, but conclusive evidence is lacking. A systematic review investigating the role of silver in acute or chronic wounds concluded that there was insufficient evidence to recommend the use of silver.(6) Despite this, it has been suggested that there are good indications for the use of silver dressings to remove or reduce an increasing bioburden in burns and open wounds healing by secondary intention, or to act as a barrier against cross-contamination of resistant organisms such as MRSA.(7)
Topical negative pressure Topical negative pressure (TNP) therapy is a relatively recent technological advance in the management of acute and chronic wounds. The open wound is covered with a contact material, and active suction is applied uniformly across the material, creating a negative pressure across the wound surface. Studies have shown that TNP may promote wound-healing factors such as better perfusion, reduction of wound oedema and stimulation of granulation tissue and cell proliferation.(8) There are an increasing number of different TNP products on the market. When used appropriately, TNP may be a useful adjunct to conventional wound management.
Scars and tissue engineering Scars are a natural part of the dermal tissue repair process and consist of networks of fibrous collagen tissue laid down in response to dermal injury, with superficial regeneration of the epidermis above. Skin scars develop following a surgical incision, and some may progress into a more prominent aggressive form: “hypertrophic” (heaped up and red, but confined to the wound edge) or “keloid” (when the scar becomes almost tumour-like and extends without the margins of the scar). They have many functional or psychological sequelae for the patients who develop them, requiring non-invasive (eg, compression therapy) to more invasive (eg, steroid injections, surgical excision) treatment approaches. None of them gives particularly good results. In addition, some patients may need psychological support. It is estimated that around 30 million surgical procedures are conducted in Europe each year.(1) Therefore, any improvement in this field may have a significant impact on patient care and health economics. The International Advisory Panel on Scar Management has recommended the use of intralesional steroid injection for hypertrophic and keloid scars. In fact, for any abnormal scars, steroid injections have been the main, but not satisfactory, treatment option.
Researchers have discovered that embryos of some animal species that are wounded early during the gestation period heal with no scar. Further investigation has led to the development of anti-scarring factors, such as transforming growth factor ß, which modify adult wound healing and reduce scarring. These new therapies have a widespread potential for use in areas such as traumatic injury, burns and cosmetic surgery, particularly when there is the functional disadvantage of a scar over a joint. In addition, they could be used in combination with scar revision surgery to remove or reduce existing unacceptable or keloid scars. These new therapies are in the early stages of human clinical trials but initial results appear promising.(9)
Other current issues
MRSA infection MRSA has emerged as a major public health concern in the past decade. Infection by MRSA may double the rate of mortality after major surgery. MRSA screening and prevention policies are costly to implement but may be offset by the prevention of resistant infections. One study of patients having orthopaedic surgery for femoral fracture has demonstrated that the cost of additional bed occupancy, antibiotic treatment and wound care in those patients with MRSA infection amounted to an additional £13,972 per patient.(10) The market for antibiotics for MRSA is experiencing significant growth but remains a largely unmet need, particularly if measures are not in place to regulate the overuse of antibiotics. The benefits of antibiotic therapy have to be balanced with its cost and side-effects. Another serious side-effect of inappropriate antibiotic use, and one that has caused significant concern, is the increasing number of Clostridium difficile infections.
Chronic wound and tissue viability Healthcare professionals have encountered significant challenges in dealing with chronic wounds that have complex healing problems. A substantial amount of resources and manpower, both in hospitals and in the community, are needed to tackle the problem. The cost of treating chronic wounds in the UK has been estimated at about £1bn per year,(11) but this estimate is almost certainly already out of date. Tissue viability is a growing specialty that deals with the management of all aspects of skin and soft tissue wounds, pressure ulcers and all forms of leg ulceration. The provision of specialist medical and nursing staff can help to improve efficiency and outcome in this field. Healthcare institutions need to meticulously assess short- and long-term outcomes and the overall cost-effectiveness when planning multidisciplinary wound management and tissue viability services.
Future strategic development
The negative clinical consequences of MRSA infections and their financial impact on healthcare are unquestionable. Some healthcare institutions are currently implementing MRSA containment or treatment policies. It is likely that MRSA infection will continue as a dominant political healthcare issue. Various national surveillance methods may provide data for future prevention, containment or treatment policies. The process of tissue repair can be considered as a link between increasing knowledge of human physiology and clinical outcomes in that optimising the physiological process may contribute towards greater clinical gains. Innovative methods using modern technology are providing, and will continue to provide, an exciting area for future developments. All healthcare providers have a responsibility to recognise the role of tissue repair and to implement policies aimed at improving the process.
- Leaper DJ, et al. Int Wound J 2004;1(4):247-73.
- Kurz A, et al. N Engl J Med 1996:334(19):1209-15.
- Melling AC, et al. Lancet 2001;358:876-80.
- Rabkin JM, et al. Arch Surg 1987;122:221-5.
- Ives CL, et al. BJS 2007;94(10):87-91.
- Vermeulen H, et al. Cochrane Database Syst Rev 2007;24(1):CD005486.
- Leaper DJ. Int Wound J 2006;3(4):282-94.
- European Wound Management Association (EWMA). Position Document: topical negative pressure in wound management. London: MEP Ltd, 2007.
- Bayat A, et al. BMJ 2003;326:88-92.
- Nixon M, et al. JBJS 2006;88-B(6):812-5.
- Harding KG, et al. BMJ 2002;19(324):160-3.