A Novel Approach Using Diels-Alder Click Chemistry to Engineer a Cartilage-Mimetic,
Human Mesenchymal Stem Cell-Laden Hyaluronic Acid-Collagen Hydrogel
Rabia Fatima, M.S.
Abstract
Osteoarthritis (OA) is a debilitating joint disorder affecting over 32 million adults in the United States. Current OA treatments are limited by short-term effectiveness and an inability to repair large defects. Therefore, a major healthcare challenge remains due to the limited regenerative capacity of articular cartilage. Tissue engineering using biomimetic hydrogels and mesenchymal stem cells (MSCs) offers a promising solution by having the potential to replicate the physicochemical signals of the native cartilage extracellular matrix (ECM). However, current hydrogel and MSC therapies encounter challenges such as inadequate mechanical strength, biodegradation on a different timeline than cell remodeling, and long-term stability under physiological conditions. We propose to address these challenges by using a bioorthogonal
Diels-Alder click chemistry approach to fabricate a biocompatible, biodegradable, and tunable hydrogel composed of hyaluronic acid (HA) and type I collagen (Col I), which mimics cartilage ECM properties. Briefly, HA and Col I are modified to express a furan group, then mixed with bismaleimide poly(ethylene glycol) (Mal-PEG-Mal), where the furan and maleimide will ‘click’ together and form a gel after 24 hours at 37°C. By adjusting the Molar ratio between furan and maleimide, we can precisely tune the mechanical and degradation properties of the hydrogels, optimizing them for cartilage tissue engineering. Our ongoing research aims to optimize hydrogel parameters and physicochemical properties to improve mechanical characteristics and mimic natural cartilage more closely. Future studies will explore how hydrogel stiffness influences the chondrogenesis of encapsulated hMSCs for cartilage regeneration.
Monday, October 7th, 2024 at 04:30 pm
CAMP 176
Rabia Fatima received her BS in Biochemistry from Kinnaird College and her MS in Industrial Biotechnology from National University of Science and Technology, Pakistan. Currently, she is a first-year Ph.D. student in the Department of Chemical and Biomolecular Engineering at Clarkson University working in the Biomaterials and Stem Cell Engineering Lab under the supervision of Dr. Bethany Almeida. Her research is focused on fabricating advanced biomaterials, such as biocompatible hydrogels and drug-delivery nanoparticles, which may serve as a therapeutic platform for treating degenerative joint diseases, such as OA.