title: Chitosan facilitates structure formation of the salivary gland by regulating the basement membrane components.
abstract: Tissue structure is important for inherent physiological function and should be recapitulated during tissue engineering for regenerative purposes. The salivary gland is a branched organ that is responsible for saliva secretion and regulation. The salivary glands develop from epithelial-mesenchymal interactions, and depend on the support of the basement membrane (BM). Chitosan-based biomaterials have been demonstrated to be competent in facilitating the formation of salivary gland tissue structure. However, the underlying mechanisms have remained elusive. In the developing submandibular gland (SMG), the chitosan effect was found to diminish when collagen and laminin were removed from cultured SMG explants. Chitosan increased the expression of BM components including collagen, laminin, and heparan sulfate proteoglycan, and also facilitated BM components and the corresponding receptors to be expressed in tissue-specific patterns beneficial for SMG branching. The chitosan effect decreased when either laminin components or receptors were inhibited, as well when the downstream signaling was blocked. Our results revealed that chitosan promotes salivary glands branching through the BM. By regulating BM components and receptors, chitosan efficiently stimulated downstream signaling to facilitate salivary gland branching. The present study revealed the underlying mechanism of the chitosan effect in engineering SMG structure formation.
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital, College of Medicine, Taipei, Taiwan; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: yangtl@ntu.edu.tw.
authors.forename: Tsung-Lin
authors.initials: TL
authors.lastname: Yang
authors.affiliation: Department of Ophthalmology, Zhongxing Branch, Taipei City Hospital, Taipei, Taiwan; Department of Ophthalmology, College of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ya-Chuan
authors.initials: YC
authors.lastname: Hsiao
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000502:physiology*; D001672:Biocompatible Materials / Q000008:administration & dosage; D048271:Chitosan / Q000008:administration & dosage*; D003094:Collagen / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D066298:In Vitro Techniques; D007797:Laminin / Q000378:metabolism*; D051379:Mice; D009024:Morphogenesis / Q000187:drug effects / Q000502:physiology; D012469:Salivary Glands / Q000187:drug effects / Q000502:physiology*
chemical_list: D001672:Biocompatible Materials; D019812:Heparan Sulfate Proteoglycans; D007797:Laminin; D003094:Collagen; D048271:Chitosan
keywords: Basement membrane; Biomaterials; Branching morphogenesis; Chitosan; Salivary gland; Tissue engineering