Abstract: The physical environment plays a critical role in modulating stem cell differentiation into specific lineages. In this study, we designed and synthesized a series of low-molecular-weight gels (LMWGs) with different moduli based on phenylboronic acid derivatives. The moduli of the LMWGs were readily tuned by varying the alkyl chain without any chemical crosslinker. The cell responses to the gels were evaluated with mesenchymal stem cell (MSCs), in respect of cell morphology, proliferation and differentiation. The prepared gels were non-toxic to MSCs, suggesting good biocompatibility. The hydrogel stiffness exerted a striking modulation effect on MSC fate decisions, where MSCs were inclined to differentiate into osteoblasts in stiff LMWGs and into chondrocytes in soft LMWGs. The pivotal elastic modulus of the LMWGs to drive MSC differentiation into osteoblastic lineage and chondrocytic lineage were approximately
20 kPa – 40 kPa and 1 kPa – 10 kPa, respectively. Overall, our results demonstrated that the modification of hydrogel stiffness via tuning the alkyl chain was a simple but effective approach to regulate MSC differentiation into specific lineage, which might have important implications in the design of LMWGs for tissue engineering applications.

Key words: phenylboronic acid, mesenchymal stem cell, osteoblast differentiation, low-molecular-weight gels, chondrocytic differentiation, alkyl chain