Engineering Functioning Salivary Glands Using Micropatterned Scaffolds

使用微图案支架工程功能唾液腺

• 批准号: 8035611
• 负责人: MELINDA LARSEN
• 金额: $ 7.6万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT ALBANY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-08 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8035611
• 关键词: Adult; Adverse effects; Affect; American; Area; Artificial Saliva; Autoimmune Diseases; Biocompatible; Bladder; Cell Line; Cells; Clinical; Collagen; Complex; Data; Dental; Dental caries; Development; Diagnosis; Differentiation Antigens; Duct (organ) structure; Ductal; Dysphasia; Embryo; Engineering; Environment; Epithelial Cells; Extracellular Matrix; Fibronectins; Future; Gland; Goals; Grant; Head and neck structure; Health; Human; Implant; Infection; Kidney; Knowledge; Laboratories; Lead; Link; Liquid substance; Lung; Mammary gland; Methods; Morbidity - disease rate; Morphology; Movement; Mucositis; Mus; Nanotechnology; Natural regeneration; Nature; Oral; Oral cavity; Organ; Oropharyngeal; Output; Pancreas; Patients; Pattern; Pharmaceutical Preparations; Polymers; Production; Prostate; Quality of life; Radiation therapy; Research; Resistance; Saliva; Salivary; Salivary Gland Tissue; Salivary Glands; Shapes; Site; Sjogren' s Syndrome; Smooth Muscle Myocytes; Structure; Surface; Symptoms; Taste Perception; Testing; Therapeutic; Tight Junctions; Tissue Engineering; Tissues; Topical application; Translational Research; Transplantation; Tube; United States; Universities; Work; Xerostomia; base; college; combinatorial; design; efficacy testing; experience; head and neck cancer patient; improved; in vivo; innovation; monolayer; mouse model; novel strategies; poly-L-lactic acid; programs; prototype; public health relevance; saliva secretion; scaffold; self assembly; self organization; three dimensional structure

DESCRIPTION (provided by applicant): The goal of this application is to engineer a complex 3D artificial salivary gland using an innovative strategy combining adult salivary gland cells with a micropatterned artificial scaffold. The long-range goal of my research program is to facilitate translational research by engineering of an artificial salivary gland for use in human patients suffering from salivary hypofunction. Head and neck radiation therapy and Sjogren's syndrome both lead to decreased saliva production following irreversible salivary gland tissue damage. In these patients, lack of saliva production causes significant morbidity due to dry mouth that results in dysphasia, dental caries, oropharyngeal infections, mucositis, and loss of taste. A novel strategy for restoring salivary flow is to replace damaged salivary tissue with engineered tissue that is composed of self-organized cells attached to a scaffold. The hypothesis tested in this application is that self-organized salivary gland functional units that are attached to a micropatterned artificial scaffold can create a functioning artificial gland. This hypothesis is based on our previous demonstration that embryonic salivary gland cells have an inherent capacity to self- organize into functional salivary gland tissue. In Aim 1, conditions will be established for growing primary adult mouse salivary gland cells, a functionalized micropatterned scaffold will be created, and conditions whereby the salivary gland cells can attach to the scaffold will be established. In the second Aim, we will assemble an engineered gland by first facilitating self-organization of the adult salivary gland cells into functional units and then attach these units to the scaffold through functionalized nucleation sites, and form a 3D artificial gland structure. The function of this artificial gland will be tested in vivo in a future R01 application. The methods used for this approach will facilitate engineering of a human artificial salivary gland and also serve as a prototype for engineering other complex branched organs such as pancreas, kidney, and lung. PUBLIC HEALTH RELEVANCE: The data obtained from this grant will advance basic scientific knowledge regarding the ability of adult salivary epithelial cells to self-organize into saliva-secreting structures when placed in a local environment consisting of the appropriate extracellular matrix composition and structure. We also create an artificial scaffold to which we can attach salivary gland cells and that will function as a conduit for delivery of saliva into the oral cavity. Together, the self-organized cells attached to the artificial scaffold will create an artificial salivary gland that will be tested for function in vivo in a future R01 application. This work will lead to a human artificial salivary gland will improve the oral, dental, and overall health of patients suffering from lack of saliva production by the salivary gland due to Sjogren's syndrome, radiation therapy, or other causes.

描述（由申请人提供）：本申请的目的是使用将成年唾液腺细胞与微图案的人工脚手架结合的创新策略来设计复杂的3D人造唾液腺。我的研究计划的远距离目标是通过工程化唾液腺的工程来促进转化研究，以用于唾液功能障碍的人类患者。头颈辐射疗法和Sjogren综合征都导致不可逆的唾液腺组织损伤后唾液产生降低。在这些患者中，缺乏唾液产生会导致口干引起明显的发病率，从而导致症状，龋齿，口咽感染，粘膜炎和味觉丧失。恢复唾液流动的一种新型策略是用工程组织替代由脚手架上的自组织细胞组成的工程组织。在此应用程序中检验的假设是，与微图案的人工支架相连的自组织唾液腺功能单元可以创建一个功能的人造腺体。该假设基于我们以前的证明，即胚胎唾液腺细胞具有自我组织到功能性唾液腺组织中的固有能力。在AIM 1中，将建立生长原代成年小鼠唾液腺细胞的条件，将创建功能化的微图案支架，并建立唾液腺细胞附着在支架上的条件。在第二个目标中，我们将通过首先促进成年唾液腺细胞的自组织为功能单位组装工程腺，然后通过功能化的成核位点将这些单元连接到支架上，并形成3D人造腺结构。该人造腺的功能将在未来的R01应用中在体内进行测试。用于这种方法的方法将促进人造唾液腺的工程，并作为工程其他复杂的分支器官（例如胰腺，肾脏和肺部）的原型。 公共卫生相关性：从这笔赠款中获得的数据将提高有关成年唾液上皮细胞自我组织为分泌唾液分泌结构的能力的基本科学知识，该结构将其放置在包括适当的细胞外基质组成和结构的当地环境中。我们还创建了一个人工支架，我们可以将唾液腺细胞附着在该脚手架上，这将充当将唾液输送到口腔中的管道。一起，附着在人工支架上的自组织细胞将产生人造唾液腺，该唾液腺将在未来的R01应用中测试在体内的功能。这项工作将导致人造唾液腺改善由于sjogren综合征，放射疗法或其他原因而导致唾液腺缺乏唾液腺患者的口服，牙齿和整体健康。

项目成果

Localization of AQP5 during development of the mouse submandibular salivary gland.

• DOI: 10.1007/s10735-010-9308-0
• 发表时间: 2011-02
• 期刊: JOURNAL OF MOLECULAR HISTOLOGY
• 影响因子: 3.2
• 作者: Larsen, Helga S.;Aure, Marit H.;Peters, Sarah B.;Larsen, Melinda;Messelt, Edward B.;Galtung, Hilde Kanli
• 通讯作者: Galtung, Hilde Kanli