ABSTRACT
A previously developed fibrin-agarose skin model-UGRSKIN-showed promising clinical results in severely burnt patients. To determine the histological parameters associated to the biocompatibility and therapeutic effects of this model, we carried out a comprehensive structural and ultrastructural study of UGRSKIN grafted in severely burnt patients after 3 months of follow-up. The grafted epidermis was analogue to native human skin from day 30th onward, revealing well-structured strata with well-differentiated keratinocytes expressing CK5, CK8, CK10, claudin, plakoglobin, filaggrin, and involucrin in a similar way to controls, suggesting that the epidermis was able to mature and differentiate very early. Melanocytes and Langerhans cells were found from day 30th onward, together with a basement membrane, abundant hemidesmosomes and lack of rete ridges. At the dermal layer, we found an interface between the grafted skin and the host tissue at day 30th, which tended to disappear with time. The grafted superficial dermis showed a progressive increase in properly-oriented collagen fibers, elastic fibers and proteoglycans, including decorin, similarly to control dermis at day 60-90th of in vivo follow-up. Blood vessels determined by CD31 and SMA expression were more abundant in grafted skin than controls, whereas lymphatic vessels were more abundant at day 90th. These results contribute to shed light on the histological parameters associated to biocompatibility and therapeutic effect of the UGRSKIN model grafted in patients and demonstrate that the bioengineered skin grafted in patients is able to mature and differentiate very early at the epithelial level and after 60-90 days at the dermal level.
ABSTRACT
A new model of tissue-engineered artificial autologous human skin developed in Andalusia is currently being transplanted into patients suffering from large burns within the Andalusian Public Healthcare System. This product is considered an advanced therapy medicinal product (ATMP) in Europe, and its clinical use implies meeting transplant and medicinal product legal requirements, being the Guidelines of Good Manufacturing Practice for ATMPs of particular importance. The preclinical research and clinical translation of the product have represented a technical, regulatory, and organizational challenge, which has taken 10 years since the first preclinical experiments were designed. Twelve patients with large burns, including 3 pediatric patients, have hitherto received artificial autologous skin grafts with an overall survival rate of 75% and positive clinical, homeostatic, and histologic results. Achieving such a milestone within our Healthcare System was possible through a multidisciplinary approach and the joint efforts of multiple publicly funded institutions and units under the coordination of the Andalusian Initiative for Advanced Therapies. In this article, we present the organizational model set up to facilitate collaboration and logistics among the professionals involved, totaling more than 80 people. The similarities between the tissue-engineered artificial autologous human skin transplant and other organ and tissue transplants, in terms of logistic requirements, reveal how regional and hospital transplant coordination have played a crucial role.
