Impact of Molecular
Dynamics of Polyrotaxanes on Chondrocytes
in Double-Network Supramolecular Hydrogels under Physiological Thermomechanical
Stimulation
posted on 2024-01-02, 20:34authored byTheofanis Stampoultzis, Vijay Kumar Rana, Yanheng Guo, Dominique P. Pioletti
Hyaline cartilage, a soft tissue enriched with a dynamic
extracellular
matrix, manifests as a supramolecular system within load-bearing joints.
At the same time, the challenge of cartilage repair through tissue
engineering lies in replicating intricate cellular–matrix interactions.
This study attempts to investigate chondrocyte responses within double-network
supramolecular hybrid hydrogels tailored to mimic the dynamic molecular
nature of hyaline cartilage. To this end, we infused noncovalent host–guest
polyrotaxanes, by blending α-cyclodextrins as host molecules
and polyethylene glycol as guests, into a gelatin-based covalent matrix,
thereby enhancing its dynamic characteristics. Subsequently, chondrocytes
were seeded into these hydrogels to systematically probe the effects
of two concentrations of the introduced polyrotaxanes (instilling
different levels of supramolecular dynamism in the hydrogel systems)
on the cellular responsiveness. Our findings unveiled an augmented
level of cellular mechanosensitivity for supramolecular hydrogels
compared to pure covalent-based systems. This is demonstrated by an
increased mRNA expression of ion channels (TREK1, TRPV4, and PIEZO1),
signaling molecules (SOX9) and matrix-remodeling enzymes (LOXL2).
Such outcomes were further elevated upon external application of biomimetic
thermomechanical loading, which brought a stark increase in the accumulation
of sulfated glycosaminoglycans and collagen. Overall, we found that
matrix adaptability plays a pivotal role in modulating chondrocyte
responses within double-network supramolecular hydrogels. These findings
hold the potential for advancing cartilage engineering within load-bearing
joints.