Tissue-engineered human skin substitutes developed from collagen-populatedhydrated gels: clinical and fundamental applications

The field of tissue engineering has opened several avenues in biomedical sc iences, through ongoing progress. Skin substitutes are currently optimised for clinical as well as fundamental applications. The paper reviews the dev elopment of collagen-populated hydrated gels for their eventual use as a th erapeutic option for the treatment of burn patients or chronic wounds: tool s for pharmacological and toxicological studies, and cutaneous models for i n vitro studies. These skin substitutes are produced by culturing keratinoc ytes on a matured dermal equivalent composed of fibroblasts included in a c ollagen gel. New biotechnological approaches have been developed to prevent contraction (anchoring devices) and promote epithelial cell differentiatio n. The impact of dermo-epidermal interactions on the differentiation and or ganisation of bio-engineered skin tissues has been demonstrated with human skin cells. Human skin substitutes have been adapted for percutaneous absor ption studies and toxicity assessment. The evolution of these human skin su bstitutes has been monitored in vivo in preclinical studies showing promisi ng results. These substitutes could also serve as in vitro models for bette r understanding of the immunological response and healing mechanism in huma n skin. Thus, such human skin substitutes present various advantages and ar e leading to the development of other bio-engineered tissues, such as blood vessels, ligaments and bronchi.