ACS Biomaterials Science & Engineering
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2025
·
IF 5.5
Shiyang Wu,Zhen Chai,Yanshen Yang,Rong Ding,Bei Gao,Chen Chen,Siyu He,Zhuofu Zhang,Wanting Wan,Rui Zou
Two-dimensional (2D) models fail to mimic a three-dimensional (3D) environment in studying mechanosensing of stem cells. Here, we present a 3D culture model to investigate how 3D matrix stiffness influences YAP activation and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) and evaluate the osteogenic potential of hydrogels in vivo. In this study, a 3D culture model with an adjustable matrix stiffness was established. In the in vitro study, first the osteogenic differentiation of hPDLSCs by the expression of OCN, ALP, COL-1, and RUNX-2 was assessed using qRT-PCR, accompanied by ALP staining, and then YAP expression was evaluated by immunofluorescence. In the in vivo study, hPDLSCs, together with gelatin methacrylate (GelMA) hydrogels of different stiffnesses, were implanted into a rat alveolar bone defect model. As matrix stiffness increased, hPDLSCs showed reduced spreading and significantly decreased expression of OCN, ALP, COL-1, RUNX-2, and YAP activation. Specifically, COL-1 expression in the low-stiffness group was 4.3-fold higher than that in the high-stiffness group, and the YAP nuclear/cytoplasmic ratio under low stiffness was 5.5-fold greater than that under high stiffness at day 7. In vivo, the soft-matrix-cell-laden group exhibited more new bone (86.04%) and collagen formation (74.43%) in the defect area than other groups at week 6. Reduced matrix stiffness likely promotes hPDLSC proliferation, spreading, and osteogenic differentiation through YAP activation, and low-stiffness GelMA hydrogels loaded with hPDLSCs significantly enhance alveolar bone regeneration in vivo.
研究领域:
生物医学工程
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干细胞研究
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组织工程
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力学生物学
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2020
·Vol. 8
·期 17
·4779-4791
·
IF 6.183
Chuanchuan Lin,Kun Xu,Ye He,Bailong Tao,Zhang Yuan,Ke Li,Xuemin Li,Zengzilu Xia,Kaiyong Cai
The paracrine function of mesenchymal stromal cells (MSCs) contributes a lot to tissue development, and it is regulated by various physical factors. Moreover, the extracellular matrix (ECM) of MSCs is dynamic, and its remodeling is always occurring. In particular, stiffness changes are prevalent. Accordingly, ECM stiffness changes may affect the paracrine function of MSCs, which has not been investigated much. In this study, for the first time, alginate hydrogels with different stiffening times were used to assess the influence of dynamic ECM stiffness changes on the paracrine function of MSCs. It was found that a stiffer matrix (14.72 ± 1.44 kPa) under static conditions without any additional treatment could significantly potentiate the paracrine function of MSCs compared to a soft matrix (2.44 ± 0.23 kPa). Furthermore, this promotion was regulated by the activation of Yes-associated protein (YAP), which was caused by the polymerization of F-actin. Intriguingly, in a dynamic system, the MSC-encapsulating matrix that stiffened on the third day had stronger YAP activation than the Static-Stiff matrix. However, this activation was weakened when MSCs were cultured in a matrix that stiffened on the fifth day. The results show that an increase in ECM mechanical dosing levels would promote the paracrine function of MSCs. Moreover, an effective mechanical dose that can influence the paracrine function of MSCs indeed exists.
研究领域:
细胞生物学
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组织工程
·
生物力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
npj Science of Food
·
2023
·Vol. 7
·期 1
·1-13
·
IF 6.4
Xu Enbo,Niu Ruihao,Lao Jihui,Zhang Shengliang,Li Jie,Zhu Yiyuan,Shi Huimin,Zhu Qingqing,Chen Yijian,Jiang Yuyan,Wang Wenjun,Yin Jun,Chen Qihe,Huang Xiao,Chen Jun,Liu Donghong
Tissue-like cultured meats of some livestock have successfully been established by different approaches. However, the production of a structure similar to fish fillets is still challenging. Here, we develop tissue-like cultured fish fillets by assembly of large yellow croaker muscle fibers and adipocytes with 3D-printed gel. Inhibition of Tgf-β and Notch signals significantly promoted myogenic differentiation of piscine satellite cells (PSCs). The mixture of fish gelatin and sodium alginate combined with a p53 inhibitor and a Yap activator supported PSC viability and proliferation. Based on the texture of fish muscle tissue, a 3D scaffold was constructed by gelatin-based gel mixed with PSCs. After proliferation and differentiation, the muscle scaffold was filled with cultured piscine adipocytes. Finally, tissue-like fish fillets with 20 × 12 × 4 mm were formed, consisting of 5.67 × 10 7 muscles and 4.02 × 10 7 adipocytes. The biomanufacture of tissue-like cultured fish fillet here could be a promising technology to customize meat production with high fidelity.
研究领域:
生物技术
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食品科学
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组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）