Piel ingenierizada para el tratamiento tópico de enfermedades cutáneasdesarrollo, producción farmacéutica y establecimiento de nuevos prototipos

Abstract

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare disease originated by mutations in the type VII collagen gene. It provokes cutaneous fragility at the level of the dermo-epidermal junction in the basement membrane zone. Starting from a clinically proven human skin construct, this Ph.D. Thesis has developed a bilayer skin equivalent adapted to Good Manufacturing Practice (GMP). To this end, we have set up and validated (i) skin production from epidermolysis bullosa patient biopsies, (ii) quality control (both in process and in the end product), and (iii) end product packaging materials and stability after distribution to Hospital. All these protocols were set up in accordance with Spanish Medicinal Product Agency. We have produced cells for a Phase II clinical trial to evaluate safety and efficacy of engineered skin therapy containing healthy donor fibroblasts in the artificial dermis. The clinical trial has finished the recruitment and treatment phases and we just finished one year follow-up of the last patient. Finally, we have improved the original skin equivalent and shown that plasma hydrogel-based adipose tissue may be engineered in vitro and that, on top of it, it may functionally interact with dermal and epidermal layers to influence the in vitro epidermal proliferation and differentiation program. This novel engineered skin trilayer might present multiple applications such as use for in vitro drug absorption tests and regenerative therapies.