2013-01-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/642825摘要：由細胞與細胞間質交互作用產生的分枝發育是腺體發育必需的過程，尤其，如唾液腺這類具有功能性的腺體再生，分枝發育的重要性是不可獲缺的。但對於其是否受到生醫材料所影響，至今尚無人探討，本實驗室在過去的研究中已發現幾丁質可以促進頜下唾液腺的分枝，本計劃則進一步探討不同生醫材料對唾液腺再生的影響以及研究生醫材料對調控頜下唾液腺分枝的機轉，這些研究結果將幫助找出促進組織工程唾液腺分枝發育的生醫材料，長期目標是開發一種人工唾液腺的新系統來治療唾液腺功能喪失。本計畫可分成下列四個目標：(目標一) 生醫材料對唾液腺分枝發育型態的影響此計劃以胚胎唾液腺為動物模型。經由觀察細胞組織的活動，探討不同生醫材料對唾液腺分枝的影響，生醫材料包括可分解與不可分解高分子，不同親疏水性高分子，混掺高分子。此外，也將探討唾液腺間質細胞與上皮細胞在不同生醫材料上的細胞特性。因為細胞移動與分枝發育密切相關，也將一併探討。(目標二) 生醫材料對分枝發育形態生成之作用如果有生醫材料可於體外培養中促進唾液腺分枝。則可藉由研究此物質的類似物或具相同化學結構的衍生物對分枝發育的影響，及其調控唾液腺的形態生成作用，來瞭解其生醫材料和組織間的交互作用。因此高分子生醫材料將進一步被改質，如去官能基與接枝不同氨基酸。(目標三) 唾液腺組織對生醫材料形態生成作用之反應因為發育型態是一連串上皮細胞與間質細胞交互作用的結果。此研究目標在測試不同生醫材料對唾液腺細胞之作用及其相關之細胞生物學之機轉。本目標欲瞭解生醫材料是否能強化細胞間質對分枝發育所扮演的角色，並在調控唾液腺上皮細胞的發育型態上與細胞間質生成因子的生物特質相互合作。(目標四) 生醫材料對唾液腺分枝發育形態生成之作用機轉此目標在檢測不同的生醫材料對唾液腺組織的分枝發育型態的作用機轉。由於唾液腺組織在組織生成中藉由許多因子的調空和交互作用，得以完成其形態學之發生。故此子計畫的目標在探索期間之作用機轉。<br> Abstract: Branching morphogenesis is an essential developmental process resulting from the interaction of cells and extracellular matrix, but whether it is influenced by biomaterials has never been explored. In the previous study, chitosan has been demonstrated to enhance branch formation of submandibular gland (SMG). The objective of present project is further to investigate the effects of different biomaterials on salivary gland regeneration and to study the mechanism of biomaterials in regulating salivary gland branching. This information may be helpful to develop appropriate biomaterials for inducing branching of tissue-engineered salivary glands for future use in the treatment of patients with salivary hypofunction. The objectives in this project will be achieved through the following specific aims.Specific Aim 1: Biomaterial effect on branching morphogenesis of salivary gland By using embryonal SMG as a model, the effect of different biomaterials on branching morphogenesis of salivary gland, a biological event in the tissue level will be assessed. The biomaterials used in this study include degradable and non-degradable polymers with different chemical properties, and blended polymers with enhanced biocompatible properties. Besides, the effect of biomaterials on the migration of both salivary mesenchymal and epithelial cells will be investigated. Specific Aim 2: Characterization of biomaterial morphogenetic properties on salivary tissue If there is any biomaterial capable of promoting SMG explants branching in the ex vivo culture system, the effects of these biomaterials and the related analogues or derivatives with similar chemical structures on salivary gland morphogenesis will be tested. Toward this aim, biomaterial surface properties will be further modified by protein coating and chemical treatment to control the behaviors of SMG explants.Specific Aim 3: Exploration of salivary tissue responses to biomaterial morphogenetic effectSince the morphogenesis is a consequence resulting from the reciprocal interaction between epithelia and mesenchyme, this specific aim will test the capacities of biomaterial to influence the SMG epithelium and mesenchyme and the related tissue interactions. It is proposed that biomaterial is competent to intensify the morphogenetic role of mesenchyme and cooperates with the biological functions of mesenchyme-derived factors in regulating SMG epithelial morphogenesis. Specific Aim 4: The underlying mechanism of biomaterial effects on branching morphogenesis of salivary tissue The intrinsic mechanisms which accounts for salivary tissue morphogenesis when it is engineered by different biomaterials will be further explored. If there is any biomaterial capable of promoting SMG explants branching in the engineering system, the change of gene expression of branching morphogen will be tested. In addition, the effect of biomaterials on exogenous supplemented factors and the interaction between the biomaterials and the intrinsic regulating factors responsible for SMG phenotypes will also be examined.唾液腺分枝發育salivary glandbranching morphogenesis