ERI: Investigating the Fundamental Interactions between Mesenchymal Stem Cells and Hydrogels – Towards a Stem Cell-Biomaterial Therapy for Osteoarthritis

ERI：研究间充质干细胞和水凝胶之间的基本相互作用 — 走向骨关节炎的干细胞生物材料疗法

• 批准号: 2138587
• 负责人: Bethany Almeida
• 金额: $ 20万
• 依托单位: Clarkson University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2138587&HistoricalAwards=false
• 关键词: ERI; Investigating; Fundamental; Interactions; between

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2). Human mesenchymal stem cells (hMSCs) have the promise to treat a wide variety of human disease conditions due to the cells’ ability to transform into many mature cell types. Stem cells also have the potential to influence immune response and wound healing. However, their promise has not yet been realized in the clinic. Recent work has explored how biomaterials can control hMSC behavior. However, how hMSCs change biomaterials over time is unknown. This Engineering Research Initiation (ERI) award will address how biomaterials change over time due to stem cells, how stem cells respond to biomaterials, and the interrelationship between the two. The results of this project may lead to improved stem cell-based therapies for conditions like osteoarthritis. The project will introduce local K-12 students to the exciting possibilities of careers in biomedical engineering through hands-on demonstrations for the Potsdam North Country Children's Museum. The project will enhance the Clarkson University curriculum through undergraduate research opportunities and a new course.The overall goal of the project is to understand how biodegradable hydrogels, mimetic of the native cartilage microenvironment, direct lineage specificity of encapsulated human mesenchymal stem cell (hMSC). This goal will be achieved by designing an hMSC-laden hydrogel capable of modulating cellular stiffness and shape and investigating the interrelationship between hydrogel physicochemical properties and stem cell culture conditions. A systematic approach will be used to fabricate a series of hydrogels with varying physicochemical properties. The specific design criteria include the polymer type, molecular weight, and concentration, presence of a known chondrogenic small molecule eluting from a polymeric nanoparticle that is incorporated into the hydrogel backbone, and the patterning and encapsulation of the hMSCs within the hydrogel. Upon fabrication of the hydrogel variations, the dynamic hydrogel physicochemical properties will be investigated in various stem cell culture conditions and the effects of the hydrogel variations on hMSC chondrogenesis will be explored. Completion of this project will result in the generation of new knowledge that may be used to guide biomaterial-stem cell therapies for treatment of osteoarthritis, as well as lay the foundation for a paradigm shift towards developing a deeper understanding of the fundamental interrelationship between biomaterial physicochemical properties and the stem cell microenvironment.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该奖项全部或部分根据2021年美国救援计划法案（公法117-2）资助。人类间充质干细胞（hMSCs）有希望治疗各种各样的人类疾病，因为细胞能够转化为许多成熟的细胞类型。干细胞还具有影响免疫反应和伤口愈合的潜力。然而，他们的承诺尚未在临床上实现。最近的工作探索了生物材料如何控制hMSC的行为。然而，hMSCs如何随着时间的推移改变生物材料是未知的。该工程研究启动（ERI）奖将解决生物材料如何随着时间的推移而变化，由于干细胞，干细胞如何响应生物材料，以及两者之间的相互关系。该项目的结果可能会改善基于干细胞的治疗方法，用于骨关节炎等疾病。该项目将通过为波茨坦北部国家儿童博物馆进行实际演示，向当地K-12学生介绍生物医学工程职业的令人兴奋的可能性。该项目将通过本科生的研究机会和一门新的课程来加强克拉克森大学的课程。该项目的总体目标是了解生物可降解水凝胶，天然软骨微环境的模拟物，包封的人间充质干细胞（hMSC）的直接谱系特异性。这一目标将通过设计能够调节细胞刚度和形状的hMSC负载水凝胶并研究水凝胶理化性质和干细胞培养条件之间的相互关系来实现。 一个系统的方法将被用来制造一系列的水凝胶具有不同的物理化学性质。具体的设计标准包括聚合物类型、分子量和浓度、从掺入水凝胶骨架中的聚合物纳米颗粒洗脱的已知软骨形成小分子的存在，以及水凝胶内hMSC的图案化和包封。在制造水凝胶变体后，将在各种干细胞培养条件下研究动态水凝胶物理化学性质，并探索水凝胶变体对hMSC软骨形成的影响。该项目的完成将产生新的知识，可用于指导生物材料干细胞疗法治疗骨关节炎，以及为发展对生物材料物理化学性质和干细胞微环境之间基本相互关系的更深入理解的范式转变奠定基础。该奖项反映了NSF的法定使命，并被认为值得通过以下方式获得支持：使用基金会的知识价值和更广泛的影响审查标准进行评估。