Membrane Drug Loading and Release for Skin Tissue Regeneration, Repair and Protection

The development of biodegradable nano-structured membranes with specific functionalities and structural features able to provide adaptable biomimetic microenvironments for the control of the cell fate, represents one of the major challenges in skin tissue engineering [1-2]. Moreover, the membrane loading with a bioactive molecule constantly released in the time represents a further strategy to trigger or modulate biological processes needed for skin regeneration and repair. In this work, microporous membranes of chitosan loaded with a natural compound with therapeutic and healing properties were developed. 18-β-Glycyrrhetic Acid (GA) is a natural derivative of licorice (Glycyrrhiza) extract, with a wide range of pharmacological activities, including anti-oxidant, anti-carcinogenic, anti-inflammatory, wound healing, and protective of aging- and UV-induced skin damages. The biomolecule was incorporated in the microporous structure of the chitosan membrane as a water-soluble inclusion complex with β-cyclodextrin (β-CD). Composite CHT membranes, with different ratio of βCD-GA inclusion complex, were realized by phase inversion process [3]. Membranes were characterized to evaluate structural, physico-chemical and biodegradation properties, and the GA incorporation and release were assessed in the time. Successively, the developed membranes were used for the formation of epidermal constructs by using human keratinocytes. The morphological behaviour, proliferation, metabolic functions, and the expression of specific cytokeratins involved in the keratinocytes differentiation, were expressed at different levels by cells cultured on native chitosan membrane, and on chitosan/βCD-GA composite membranes. Moreover, the protective effect of the GA was assessed after UV and oxidative stress damages induced in the developed epidermal membrane constructs, highlighting the pivotal protective role played by GA incorporated and released in the chitosan/βCD-GA membrane system. These achievements represent an attractive tissue engineering approach for the creation of membrane skin models that incorporate bioactive molecules useful in the tissue regeneration processes, and that could be used as a patch for topical drug delivery, wound healing and skin repair.