Polyethylene glycol Hydrogels for Salivary Gland Regeneration

用于唾液腺再生的聚乙二醇水凝胶

• 批准号: 8831776
• 负责人: Andrew Dean Shubin
• 金额: $ 2.84万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-01 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8831776
• 关键词: Address; Adsorption; Affect; Basement membrane; Biocompatible Materials; Biologic Characteristic; Biological Factors; Cancer Etiology; Cancer Survivor; Cell Adhesion; Cell Communication; Cell Proliferation; Cell Survival; Cell Transplantation; Cell Transplants; Cell secretion; Cells; Characteristics; Chemicals; Chemistry; Clinical; Complement; Cues; Defect; Dental Hygiene; Dental caries; Development; Diagnosis; Diet; Duct (organ) structure; Encapsulated; Ensure; Enzymes; Ethylene Glycols; Experimental Designs; Extracellular Matrix; Functional disorder; Future; Geometry; Gland; Head and Neck Cancer; Healed; Histology; Hydrogels; Image; Impairment; In Situ; In Vitro; Inflammation; Injection of therapeutic agent; Injury; Investigation; Knowledge; Laminin; Lead; Ligation; Link; Maintenance; Matrix Metalloproteinases; Measures; Mechanics; Mediating; Medical; Membrane Proteins; Methods; Microspheres; Modeling; Mus; Natural regeneration; Nature; Organ; Pain; Patients; Phenotype; Physicians; Polyethylene Glycols; Proliferating; Property; Proteins; Quality of life; Radiation; Radiation therapy; Reactive Oxygen Species; Recovery; Reporting; Research; Research Training; Saliva; Salivary; Salivary Gland Tissue; Salivary Glands; Scientist; Speech; Submandibular gland; Sulfhydryl Compounds; Suspension Culture; Testing; Therapeutic; Tissue Engineering; Tissues; Training; Transplantation; Wild Type Mouse; Work; Writing; Xerostomia; base; cancer therapy; design; ethylene glycol; experience; functional restoration; healing; improved; in vivo; insight; irradiation; novel; novel therapeutic intervention; photopolymerization; polymerization; public health relevance; regenerative; regenerative therapy; response; restoration; saliva secretion; scaffold; soft tissue; technology development; tissue regeneration

 DESCRIPTION (provided by applicant): Over 40,000 patients in the U.S. are diagnosed with head and neck cancers annually. Radiation therapy for these cancers causes irreparable damage to the salivary glands resulting in permanent xerostomia or dry mouth. Xerostomia significantly detracts from patient quality of life by adversely impacting oral hygiene, and currently no regenerative therapy exists to restore proper saliva secretion. Recent work has demonstrated that direct injection of primary submandibular gland (SMG) cells prepared by suspension culture into a radiation damaged glands leads to modest recovery of gland function in vivo. Thus, we aim to develop a biomaterials approach to augment gland recovery after irradiation by supporting SMG survival and function. Hydrogels, which are hydrophilic and bio-inert, have mechanical properties that are similar to those seen in soft tissues; however, few investigations have been reported regarding hydrogel-mediated salivary gland regeneration approaches. This project seeks to address this gap in knowledge by exploring the use of poly(ethylene glycol) (PEG) hydrogels as a means to transplant submandibular gland cells and regenerate functional salivary tissue. PEG hydrogels can be functionalized with both degradable and bioactive moieties to enhance the regenerative potential of SMG cells and can be formed in situ using photopolymerization. This project aims to develop permissive hydrogel encapsulation methods for primary salivary gland cells, design hydrogel milieus to promote salivary gland regeneration through cell-material interactions, and to form hydrogels in situ for salivary gland cell transplantation and gland regeneration. To design cytocompatible encapsulation methods, the effects of different types of hydrogel polymerizations on therapeutic SMG cells will be assessed in Aim 1. Cytocompatible PEG hydrogels chemistries will be further modified in Aim 2 to include cell-dictated degradability as well as vital cell adhesion motifs found in the salivary gland extracellular matrix (ECM) to improve the regenerative potential of the hydrogel scaffold. In Aim 3 SMG cells will be transplanted using in situ photopolymerization in both duct ligation and radiation models of salivary gland injury to track cell incorporation and functional gland recovery. Completion of these aims will determine the feasibility of hydrogel encapsulation for SMG based therapies and approach for tissue engineering approaches for the salivary gland. Detailed within this application are activities to complement the research training of the applicant. Both sponsors are dedicated to the applicant's development as a physician-scientist and will continue to train the applicant in experimental design, scientific writing, and presentation. The applicant will also pursue two longitudinal clinical experiences with physicians working in cancer treatment to gain a better understanding of the clinical context of his research. Finally, the applicant will continue involvement in the development of future studies during his medical training.

 描述（由申请人提供）：美国每年有超过40，000名患者被诊断患有头颈癌。这些癌症的放射治疗会对唾液腺造成不可修复的损伤，导致永久性口干或口干。口干症通过不利地影响口腔卫生而显著降低患者的生活质量，并且目前不存在恢复适当唾液分泌的再生疗法。最近的工作表明，直接注射的原代下颌下腺（SMG）细胞制备的悬浮培养到辐射损伤的腺体导致适度恢复腺体功能在体内。因此，我们的目标是开发一种生物材料方法，通过支持SMG存活和功能来增加照射后的腺体恢复。水凝胶是亲水性和生物惰性的，具有与软组织中所见相似的机械性质;然而，关于水凝胶介导的唾液腺再生方法的研究报道很少。该项目旨在通过探索使用聚乙二醇（PEG）水凝胶作为移植下颌下腺细胞和再生功能性唾液组织的手段来解决这一知识差距。PEG水凝胶可以用可降解和生物活性部分官能化以增强SMG细胞的再生潜力，并且可以使用光聚合原位形成。本项目旨在开发适用于原代涎腺细胞的水凝胶包封方法，设计水凝胶微环境以通过细胞-材料相互作用促进涎腺再生，并原位形成水凝胶用于涎腺细胞移植和腺体再生。为了设计细胞相容的包封方法，将在目的1中评估不同类型的水凝胶聚合对治疗性SMG细胞的影响。细胞相容性PEG水凝胶化学将在目标2中进一步修改，以包括细胞决定的降解性以及在唾液腺细胞外基质（ECM）中发现的重要细胞粘附基序，以提高水凝胶支架的再生潜力。在目标3中，将使用原位光聚合在导管结扎和唾液腺损伤的辐射模型中移植SMG细胞，以跟踪细胞掺入和功能性腺体恢复。这些目标的完成将确定水凝胶包封用于基于SMG的治疗的可行性和用于唾液腺的组织工程方法的方法。本申请中详细介绍了补充申请人研究培训的活动。两个赞助商都致力于申请人作为一个医生，科学家的发展，并将继续培训申请人在实验设计，科学写作和演示。申请人还将与从事癌症治疗的医生一起追求两个纵向临床经验，以更好地了解其研究的临床背景。 最后，申请人将继续参与其医学培训期间未来研究的发展。