The ReCell Spray‑On Skin system for treating skin loss, scarring and depigmentation after burn injury

The ReCell Spray‑On Skin system (Avita Medical; 'ReCell') is a rapid, autologous cell harvesting, processing and delivery system for treating skin loss and preventing scarring and depigmentation in adults and children with burns. ReCell Spray‑On Skin is prepared by shaving a 0.15 mm to 0.20 mm‑thick piece of skin, measuring up to 2 cm by 2 cm, from a donor site close to the burn. The donor skin is added to a proprietary enzyme solution (derived from pigs) in a processing unit and heated for 15 to 30 minutes to disaggregate the cells. The skin is then removed and scraped with a scalpel to develop a plume of cells. These cells are added to a buffer solution, aspirated and filtered to create a cell suspension that contains keratinocytes, melanocytes, fibroblasts and Langerhans cells. The suspension is delivered to the debrided burn using a spray applicator, or it can be dripped directly onto the site. It is designed so that cells from the suspension are able to proliferate rapidly and migrate in the wound bed. The regenerative nature of these skin cells is intended to promote the growth of healthy skin to achieve rapid healing. The procedure is designed to be carried out by clinicians, without input from specialised laboratory staff.

ReCell is supplied as a sterile pack containing all the components needed to create and apply a skin cell suspension sufficient to treat burn injuries up to 320 cm². The cost of ReCell stated in the sponsor's submission is £950 plus VAT per pack.

The claimed benefits of ReCell in the case for adoption presented by the sponsor are:

• A reduction in the size and depth of the skin graft donor site.

• Shorter healing time, fewer complications and reduced morbidity at the donor site.

• Shorter healing time at the recipient site, leading to:

  • improved aesthetic results for burn wounds, with a reduced likelihood of scarring

  • reduced likelihood of later readmission to hospital for corrective surgery as a result of improved aesthetic results.

• Repopulation of melanocytes to reduce hypopigmentation and improve skin colour match in healed wounds.

• Reduced frequency of dressing changes to weekly rather than daily, allowing for a shorter stay in hospital and outpatient management.

• Reduced need for dressing changes under anaesthetic.

• A reduction in the need for external technical laboratory support.

The treatment of burns can be considered in 2 phases: acute and reconstructive. The acute phase is the initial management of the burn wound, where the aim is to heal with minimal scarring and physical limitation. The reconstructive phase aims to improve the functional or visual effect of scarring, usually by surgical means, and may be done months or years after the initial injury.

The first step in managing a burn is to assess the site of the injury, the proportion of the body surface area involved and the burn depth. The extent of a burn is usually expressed as a proportion of the total body surface area affected. Burn depth is classified according to the layer of skin (epidermis, dermis or subcutaneous layer) affected. Burns can be classified as:

• epidermal or superficial, affecting the epidermis only, as in cases of sunburn

• partial thickness or dermal, affecting the dermis and stratified into superficial, mid‑dermal or deep

• full thickness, where the epidermis, dermis and subcutaneous layer, and in some cases the underlying muscle or bone, are affected.

Superficial epidermal burns and full thickness burns are easily identifiable by experienced clinicians, but burn depth can be more difficult to assess accurately in partial‑thickness burns and in children because they have thin skin. Burn depth is usually assessed by clinical evaluation using visual and tactile assessment. When burn depth is uncertain, NICE recommends assessing it using the moorLDI2 Burns Imager: a laser doppler blood flow imager for burn wound assessment in its medical technologies guidance. Burns can be of mixed depths within a single injury site and can be dynamic, becoming deeper over time, depending on the cause and initial treatment. Burns of uncertain depth are often classed as indeterminate or intermediate.

Epidermal and superficial partial thickness burns tend to heal without scarring or surgical intervention within 21 days. Mid‑dermal or deep partial thickness burns and full thickness burns may need surgical excision or debridement to remove the burnt skin and tissues. It is usual for surgical excision to be done within 48 hours of admission to hospital. The burn wounds are then dressed with conventional or biosynthetic dressings or skin grafts in more serious burns. Skin grafting is used to promote rapid healing, to minimise scarring and to reduce complications. Healing can occur only from the edges of a burn wound, so without a skin graft the wound can contract. This contraction and formation of scar tissue can lead to a poor cosmetic outcome and reduced mobility. Skin grafting grafts is often used to treat mid‑dermal or deep partial thickness burns. For mixed‑depth burns, or if there is uncertainty over depth, a decision about whether to use skin grafting is based on assessment of burn healing and the patient's condition, between 10 and 21 days after the injury. Delayed healing (more than 21 days) increases the probability of hypertrophic scarring. Full thickness burns more than 1 cm in diameter will always need skin grafting because the regenerative components of the skin have been lost.

Skin grafts may be classified as partial or full thickness grafts, depending on how much of the dermis is harvested by the surgeon. The clinical 'gold standard' for skin grafting is an autologous (from the patient's own skin) split‑thickness graft taken from an area of unburnt skin. Grafts should ideally be taken from donor sites adjacent to the injury to improve the match with the surrounding skin. However, the size and location of the burn injury can limit the choice of donor site, so grafts may be taken from other areas of the body. The donor site is itself a wound and needs treatment to ensure healing. If large grafts are needed for extensive burns, the donated skin can be perforated (or meshed) to increase its surface area. The mesh ratio differs depending on the area needing coverage and is generally between 1:1.5 and 1:4 times the original skin size. The pattern of meshing can be visible after healing, so sheet (non‑meshed) grafting is preferable for a good cosmetic result.

Alternatives to autologous skin grafts for deep partial thickness and extensive full thickness burns include bio‑engineered skin substitutes, that may be cultured autologous skin cells (epithelial autografts), synthetic dermal substitutes or artificial membranes. Cultured epithelial autografts need cells (usually keratinocytes) from a donor site to be grown in vitro either as sheets or in a liquid suspension. Culturing can take days or weeks and cells are then applied directly to the wound or can be attached to synthetic or biological carriers such as silicone, collagen or fibrin glue. Cultured skin cells can also be used in conjunction with other dermal substitutes or autologous grafts in full thickness injuries.