Application of chitin-based biomaterials to regulate the basement membrane dynamics for engineering epithelial structure formation

摘要

Tissue structure is important for inherent physiological function of epithelial organs, and also critically required in organ regeneration when tissue is engineered. Many essential organs responsible for secretion, nutrition supply, or metabolite exchange, are featured and benefited by ramified tissue architecture during organogenesis. For the purpose of tissue engineering, formation of tissue structures are still challenging. The salivary gland is a typical epithelial organ important for saliva secretion and regulation. The salivary glands develop from epithelial-mesenchymal interaction, and accordingly depend on the support of basement membrane (BM). It is therefore hypothesized that regulation of BM components by biomaterial may facilitate the tissue structure formation. Chitin-based biomaterials had been demonstrated to be competent in facilitating tissue structural formation of the salivary glands. Using the developing submandibular gland as a model, it was found that chitosan effect diminished when BM components were removed from cultured SMG explants. With chitosan, BM components and receptors increased, and expressed in tissue-specific manners beneficial for SMG branching. Chitosan effect decreased when either BM components or receptors were removed, and reduced as well when downstream signaling of BM components and receptors was blocked. Our results revealed that the morphogenetic effect of chitosan on salivary glands branching is through the regulation of the dynamics of BM components. This study revealed the underlying mechanism accounting for chitin-based biomaterial effect in engineering branching structure formation of the salivary glands, which paves ways for further optimization and application of chitin-based biomaterials in facilitating structure formation of epithelial organs.