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）：本申请的目标是使用将成人唾液腺细胞与微图案人工支架相结合的创新策略来设计复杂的 3D 人工唾液腺。我的研究计划的长期目标是通过人工唾液腺工程来促进转化研究，以用于患有唾液功能减退的人类患者。头颈放射治疗和干燥综合征都会导致唾液腺组织损伤，导致唾液分泌减少。在这些患者中，唾液分泌不足会导致严重的口干症，从而导致言语困难、龋齿、口咽感染、粘膜炎和味觉丧失。恢复唾液流动的一种新策略是用由附着在支架上的自组织细胞组成的工程组织替代受损的唾液组织。本申请测试的假设是，附着在微图案人工支架上的自组织唾液腺功能单元可以创建功能性人工腺体。这一假设基于我们之前的证明，即胚胎唾液腺细胞具有自组织成功能性唾液腺组织的固有能力。在目标 1 中，将建立原代成年小鼠唾液腺细胞生长的条件，将创建功能化的微图案支架，并建立唾液腺细胞可以附着到支架上的条件。在第二个目标中，我们将通过首先促进成体唾液腺细胞自组织成功能单元来组装工程腺体，然后通过功能化成核位点将这些单元附着到支架上，并形成3D人工腺体结构。这种人工腺体的功能将在未来的 R01 应用中进行体内测试。这种方法所使用的方法将有助于人类人工唾液腺的工程设计，并且还可作为工程设计其他复杂分支器官（如胰腺、肾脏和肺）的原型。 公共健康相关性：从这项资助中获得的数据将推进有关成人唾液上皮细胞在放置在由适当的细胞外基质组成和结构组成的局部环境中时自组织成唾液分泌结构的能力的基础科学知识。我们还创建了一个人造支架，我们可以将唾液腺细胞附着在其上，并将其用作将唾液输送到口腔中的导管。附着在人工支架上的自组织细胞一起将创建一个人工唾液腺，该唾液腺将在未来的 R01 应用中进行体内功能测试。这项工作将导致人类人工唾液腺改善因干燥综合征、放射治疗或其他原因导致唾液腺分泌不足的患者的口腔、牙齿和整体健康。

项目成果

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

AQP5 在小鼠颌下唾液腺发育过程中的定位。

• 发表时间: 2011-02
• 影响因子: 3.2
• 作者: Larsen, Helga S;Aure, Marit H;Peters, Sarah B;Larsen, Melinda;Messelt, Edward B;Kanli Galtung, Hilde
• 通讯作者: Kanli Galtung, Hilde