Control of MSC Differentiation by Tuning the Alkyl Chain Length of Phenylboroinc Acid Based Low-molecular-weight Gelators
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.
Keywordslow-molecular-weight gels phenylboronic acid alkyl chain mesenchymal stem cell osteoblast differentiation chondrocytic differentiation
Unable to display preview. Download preview PDF.
This work was supported by the Natural Science Foundation grants (Nos. 31600765 and 21672164), Natural Science Foundation of Zhejiang Province (No. LY15B020001), Sichuan Province Miaozi Project (No. 2016RZ0032), and Chinese Postdoctoral Science Foundation (2016M062690).
- Lim H J, Mosley M C, Kurosu Y, Callahan L A S. Concentration dependent survival and neural differentiation of murine embryonic stem cells cultured on polyethylene glycol dimethacrylate hydrogels possessing a continuous concentration gradient of n-cadherin derived peptide His-Ala-Val-Asp-Lle. Acta Biomaterialia, 2017, 56, 153–160.CrossRefGoogle Scholar
- He J, Meng G, Yao R, B. Jiang B, Y. Wu Y, F. Wu F. The essential role of inorganic substrate in the migration and osteoblastic differentiation of mesenchymal stem cells. Journal of the Mechanical Behavior Biomedical Materials, 2016, 59, 353–365.Google Scholar