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

Clarkson University, Potsdam NY

Investigators

Abstract

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.