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

该奖项的全部或部分资金来自《2021年美国救援计划法案》(公法117-2)。人骨髓间充质干细胞(HMSCs)具有转化为多种成熟细胞的能力，有望治疗多种人类疾病。干细胞也有可能影响免疫反应和伤口愈合。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尚不清楚。该工程研究启动(ERI)奖将阐述干细胞如何随着时间的推移改变生物材料，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导致改进基于干细胞的治疗方法，以治疗骨关节炎等疾病。该项目将通过波茨坦北部国家儿童博物馆的实践演示，向当地的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可生物降解水凝胶是如何模拟天然软骨微环境，直接识别包裹的人骨髓间充质干细胞(HMSC)的谱系特异性的。这一目标将通过设计一种能够调节细胞硬度和形状的hMSC水凝胶来实现，并研究水凝胶的物理化学性质与干细胞培养条件之间的相互关系。一种系统的方法将被用来制备一系列具有不同物理化学性质的水凝胶。具体的设计标准包括聚合物的类型、相对分子质量和浓度、从被结合到水凝胶骨架中的聚合物纳米颗粒中洗脱出的已知成软骨小分子的存在，以及hMSCs在水凝胶中的图案化和封装。在制备了不同类型的水凝胶后，将研究不同干细胞培养条件下的动态水凝胶的物理化学性质，并探讨不同类型的水凝胶对hMSC软骨形成的影响。该项目的完成将产生新的知识，可用于指导骨关节炎的生物材料-干细胞疗法，并为范式转变奠定基础，以便更深入地了解生物材料的物理化学性质和干细胞微环境之间的基本相互关系。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.