Author:
Stampoultzis Theofanis,Rana Vijay Kumar,Guo Yanheng,Pioletti Dominique P.
Abstract
AbstractHyaline 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 hydrogels, tailored to mimic the dynamic molecular nature of hyaline cartilage. To this end, we infused non-covalent 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 varied concentrations of introduced polyrotaxanes (instilling different levels of supramolecular dynamism in the hydrogel systems) on 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, PIEZO1), signaling molecules (SOX9) and matrix remodeling enzymes (LOXL2). Such outcomes were further elevated upon external application of biomimetic thermomechanical loading that 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 potential for advancing cartilage engineering within load-bearing joints.Graphical AbstractDouble network supramolecular hydrogels enhanced chondro-induction significantly compared to purely covalent-based hydrogels as indicated by enhanced accumulation of extracellular matrix molecules.
Publisher
Cold Spring Harbor Laboratory