Tissue-Engineered Skin in Burn Management and Research, How to Collect the Evidence

The functionally and cosmetically best therapeutic option for the treatment of full thickness skin defects is transplantation of full thickness autologous skin. This option is limited due to donor-site availability with respect to size and morbidity. Coverage of extended lesions therefore still poses a significant challenge, and outcome is often suboptimal in terms of scarring. Although skin cells have been cultured since decades, there are no commercially available autologous, patient’s own cultured skin constructs for clinical use in the treatment of burns and large acute full thickness skin defects today. In the past, epidermal cell cultures were applied, but lacked success since no dermal component was present.

Tissue-engineered skin offers significant advantages over ‘classical’ cultured epithelial autografts (CEA), in providing a dermal component next to the epidermal coverage. Furthermore, recent advances allow introduction of other skin elements such as endothelial cells for blood vessel development, lymphatic capillaries, nerve cells as well as new hair development.

Translation of these laboratory developments to the clinical setting poses new demands, both on the development side – all products used to make the skin construct need to be compliant with clinical use – and on the application side – how do we prove that this product is actually better than the standard of care? Furthermore, these products fall into the category of Advanced Therapy Medicinal Products (ATMP’s), which brings along further regulatory burden.

To collect clinical evidence, we provide some non-invasive outcome measures that can be of use in clinical trials on skin and scar management. Wound healing as well as scar outcome parameters are valuable in conducting such trials. We previously used take and epithelialization as wound healing parameters, and  POSAS, skin elasticity parameters, scar colour parameters as well as surface roughness measurements as quantitative scar measurements in a trial on an ATMP skin construct.

Our data support the use of cultured autologous cells in treatment of extensive burns. However, regulatory issues and international law pose complicated, not internationally uniform and time consuming demands on the use of ATMP constructs.

This lecture is presented by Prof. Esther Middelkoop, Netherlands