Burn injury is a devastating trauma with systemic consequences. Although survival rates are increasing, burn injury remains a great challenge in the field of cutaneous wound healing. Major burn patients lack enough skin to cover their burns and the currently used cutaneous substitutes and cultured epithelial autograftsare still neither efficient nor effective solutions.

Transplanted skin from donors is currently not an option due to rejection; however, augmenting immunotolerance via stem cell therapy may overcome this problem. Regenerative medicine using stem cells is an efficient, low-morbidity and high-quality therapy for skin coverage in burns, mainly due to the regeneration of skin appendages and the minimal risk of hypertrophic scarring. Furthermore, stem cells may be able to address the other systemic effects of burn injury, such as hyper metabolism and inflammation.

Cell therapy has been used to treat burns since the introduction of composite epithelial autografts by Green in 1975, evolving to dermal substitutes, later on to dermal-epidermal bio-engineered cultured skin substitutes and eventually to stem cells. Stem cell therapy after burn injury emerges as a promising treatment strategy, not only for wound healing, but also to treat systemic effects of burn trauma, the hyper metabolic response, inflammation and immunosuppression.Stem cell therapy may offer an alternative to large volume resuscitation and be an adjunct to lung-protective ventilation strategies after severe burn injury.

For the treatment of acute and chronic non-healing wounds (not burn related), combined gene delivery with stem cell therapy appears promising. Gene therapy involves the insertion of a gene into recipient cells by viral transfection, naked DNA application, high pressure injection or liposomal vectors. Sequential growth factor gene therapy delivers a cocktail of growth factor genes at strategic time points of wound healing.

To enhance the therapeutic response after stem cell treatment in burn patients, intense tissue engineering with the development of 3D scaffolds or matrices is of vital importance, as well as improved preconditioning cell treatments and optimized culture conditions.

If we focus on wound healing, application of cells to the burn wound could be performed, either by the bedside as a non-invasive procedure, or in the operating room, immediately after debridement. The cells should be transferred on a matrix, scaffold or dermal substitute. One method is to first spray cells onto the wound with fibrin sealant and afterwards cover with a dermal substitute, skin graft or film. The cover over the cells acts not only as a temporary dressing, but also to theoretically enhance cell paracrine signaling and homing of the cells, improving wound healing. Although the use of cell administration using spray technologies is currently being performed in the clinical setting, there are no conclusive data to support its validity as a matrix vehicle.