Thermomagneto-responsive injectable hydrogel for chondrogenic differentiation of mesenchymal stem cells

Damaged cartilage tissue has a limited ability to self-heal due to its avascular nature and low cellularity. To effectively engineer cartilage tissue, innovative techniques such as injectable and interactive hydrogels using a minimally invasive approach are required to mimic the natural properties of cartilage. In this study, an injectable hydrogel containing magnetic iron oxide nanoparticles (MNPs) has been rationally designed to induce chondrogenic differentiation in bone marrow mesenchymal stem cells (BMSCs) using an external magnetic field application. The effect of the incorporation of MNPs with the surface functional group of either carboxyl or amine on the properties of the hydrogels (denoted as HS and HA samples, respectively) has been investigated, and compared to control hydrogel without MNPs (denoted as H). The hydrogels demonstrated thermomagnetic-responsive and shear-thinning behavior. Incorporating MNPs in the hydrogel combination resulted in the formation of a more robust network with increased compressive modulus (by 2 and 2.5 times), cell viability (by 24 % and 7 %), swelling ratio (by 97 % and 42 %) for HS and HA, respectively, as well as better cell adhesion. Also, incorporating MNPs resulted in decreased elastic modulus (by 28 and 5 times), biodegradation rate (by 5 % and 9 %), and viscosity (by 4 and 20 times) for HS and HA, respectively. The results of glycosaminoglycans (GAG) staining indicated the synergistic effect of MNP incorporation and magnetic field application in improving chondrogenic differentiation of BMSCs in vitro. The research findings could lead to the development of superior injectable hydrogels and bioinks for tissue engineering applications.