Engineering Cartilage-Mimetic hMSC-Laden Hydrogels via Diels-Alder
Bioorthogonal Click Chemistry for Cartilage Tissue Regeneration
Rabia Fatima, M.S.
Abstract
Osteoarthritis (OA) is a debilitating joint disorder that affects over 32.5 million adults in the
United States. Current OA treatments are constrained by short-term efficacy and the inability
to facilitate the repair of large cartilage defects. Consequently, the limited regenerative capacity
of articular cartilage remains a significant clinical challenge. Tissue engineering strategies
employing biomimetic hydrogels and mesenchymal stem cells (MSCs) present a promising
approach by mimicking the physicochemical cues of the native cartilage extracellular matrix
(ECM). However, existing hydrogel and MSC-based therapies face limitations, including
insufficient mechanical properties, poor cytocompatibility, mismatched biodegradation rates
relative to cellular remodeling, and compromised long-term stability under physiological
conditions. We propose to address these challenges by using a bioorthogonal Diels-Alder click
chemistry-based hydrogel platform composed of hyaluronic acid (HA) and type I collagen (Col
I), designed to replicate key structural and biochemical features of the cartilage ECM. The
hydrogels are fabricated using furan-functionalized HA (HA-furan), furan-functionalized type
I collagen (Col-furan), and bis-maleimide-functionalized polyethylene glycol (mal-PEG-mal)
under physiological conditions at 37 °C for 24 hours without the need for catalysts or initiators.
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. Notably, the incorporation of Col introduces native Arg-Gly-Asp (RGD) motifs,
enhancing bioactivity and promoting cell-matrix interactions. Collectively, this bioactive,
biodegradable, and mechanically tunable hydrogel platform provides a promising avenue for
the fabrication of ECM-inspired biomaterials for treating degenerative joint diseases, such as
OA.
Thursday, July 10th, 2025, at 11:00 am
CAMP 372
Rabia Fatima received her BS in Biochemistry from Kinnaird
College and her MS in Industrial Biotechnology from the National
University of Science and Technology, Pakistan. Currently, she is a
second-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.