Amino acid-based supramolecular chiral hydrogels promote osteogenesis of human dental pulp stem cells via the MAPK pathway

• Published in: Materials today bio Vol. 25; p. 100971
• Main Authors: Li, Peilun, Jin, Qiaoqiao, Zeng, Kangrui, Niu, Chenguang, Xie, Qianyang, Dong, Ting, Huang, Zhengwei, Dou, Xiaoqiu, Feng, Chuanliang
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2024; Elsevier
• Subjects: Bone regeneration; Bone tissue engineering; Cell differentiation; Chiral supramolecular hydrogels; Full Length; Human dental pulp stem cells; Human dental pulp stem cells; Bone tissue engineering; Cell differentiation; Bone regeneration; Chiral supramolecular hydrogels
• ISSN: 2590-0064; 2590-0064
• DOI: 10.1016/j.mtbio.2024.100971

Critical-size defects (CSDs) of the craniofacial bones cause aesthetic and functional complications that seriously impact the quality of life. The transplantation of human dental pulp stem cells (hDPSCs) is a promising strategy for bone tissue engineering. Chirality is commonly observed in natural biomolecules, yet its effect on stem cell differentiation is seldom studied, and little is known about the underlying mechanism. In this study, supramolecular chiral hydrogels were constructed using L/d-phenylalanine (L/D-Phe) derivatives. The results of alkaline phosphatase expression analysis, alizarin red S assay, as well as quantitative real-time polymerase chain reaction and western blot analyses suggest that right-handed D-Phe hydrogel fibers significantly promoted osteogenic differentiation of hDPSCs. A rat model of calvarial defects was created to investigate the regulation of chiral nanofibers on the osteogenic differentiation of hDPSCs in vivo. The results of the animal experiment demonstrated that the D-Phe group exhibited greater and faster bone formation on hDPSCs. The results of RNA sequencing, vinculin immunofluorescence staining, a calcium fluorescence probe assay, and western blot analysis indicated that L-Phe significantly promoted adhesion of hDPSCs, while D-Phe nanofibers enhanced osteogenic differentiation of hDPSCs by facilitating calcium entry into cells and activate the MAPK pathway. These results of chirality-dependent osteogenic differentiation offer a novel therapeutic strategy for the treatment of CSDs by optimising the differentiation of hDPSCs into chiral nanofibers. [Display omitted] •Chirality is a critical factor affecting the development and function of mesenchymal stem cells.•This study demonstrated that right-handed D-Phe hydrogel significantly promoted osteogenic differentiation of hDPSCs.•The D-Phe fibers promoted entry of calcium into cells and subsequent activation of the MAPK signaling pathway.•The L-Phe fibers enhanced adhesion of hDPSCs.•This report is the first to reveal the regulation effect and mechanisms of chiral supramolecular hydrogel on hDPSCs.