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Advanced Science · 2023 · IF 15.1

Tough Gelatin Hydrogel for Tissue Engineering

Ximin Yuan,Zhou Zhu,Pengcheng Xia,Zhenjia Wang,Xiao Zhao,Xiao Jiang,Tianming Wang,Qing Gao,Jie Xu,Debin Shan,Bin Guo,Qingqiang Yao,Yong He

Tough hydrogel has attracted considerable interest in various fields, however, due to poor biocompatibility, nondegradation, and pronounced compositional differences from natural tissues, it is difficult to be used for tissue regeneration. Here, a gelatin-based tough hydrogel (GBTH) is proposed to fill this gap. Inspired by human exercise to improve muscle strength, the synergistic effect is utilized to generate highly functional crystalline domains for resisting crack propagation. The GBTH exhibits excellent tensile strength of 6.67 MPa (145-fold that after untreated gelation). Furthermore, it is directly sutured to a ruptured tendon of adult rabbits due to its pronounced toughness and biocompatibility, self-degradability in vivo, and similarity to natural tissue components. Ruptured tendons can compensate for mechanotransduction by GBTH and stimulate tendon differentiation to quickly return to the initial state, that is, within eight weeks. This strategy provides a new avenue for preparation of highly biocompatible tough hydrogel for tissue regeneration.

CAS / MDL: 9000-70-8
研究领域: 生物材料 · 组织工程 · 生物医学工程
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Advanced Science · 2023 ·Vol. 10 ·期 17 ·2206814 · IF 15.1

Material Stiffness in Cooperation with Macrophage Paracrine Signals Determines the Tenogenic Differentiation of Mesenchymal Stem Cells

Renwang Sheng,Jia Liu,Wei Zhang,Yifan Luo,Zhixuan Chen,Jiayu Chi,Qingyun Mo,Mingyue Wang,Yuzhi Sun,Chuanquan Liu,Yanan Zhang,Yue Zhu,Baian Kuang,Chunguang Yan,Haoyang Liu,Ludvig J. Backman,Jialin Chen

Stiffness is an important physical property of biomaterials that determines stem cell fate. Guiding stem cell differentiation via stiffness modulation has been considered in tissue engineering. However, the mechanism by which material stiffness regulates stem cell differentiation into the tendon lineage remains controversial. Increasing evidence demonstrates that immune cells interact with implanted biomaterials and regulate stem cell behaviors via paracrine signaling; however, the role of this mechanism in tendon differentiation is not clear. In this study, polydimethylsiloxane (PDMS) substrates with different stiffnesses are developed, and the tenogenic differentiation of mesenchymal stem cells (MSCs) exposed to different stiffnesses and macrophage paracrine signals is investigated. The results reveal that lower stiffnesses facilitates tenogenic differentiation of MSCs, while macrophage paracrine signals at these stiffnesses suppress the differentiation. When exposed to these two stimuli, MSCs still exhibit enhanced tendon differentiation, which is further elucidated by global proteomic analysis. Following subcutaneous implantation in rats for 2 weeks, soft biomaterial induces only low inflammation and promotes tendon-like tissue formation. In conclusion, the study demonstrates that soft, rather than stiff, material has a greater potential to guide tenogenic differentiation of stem cells, which provides comprehensive evidence for optimized bioactive scaffold design in tendon tissue engineering.

CAS / MDL: 30525-89-4
研究领域: 生物材料 · 组织工程 · 细胞生物学 · 免疫学
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Journal of Materials Chemistry B · 2024 · IF 6.1

3D-Printed Biomimetic Scaffold Loaded with ADSCs and BMP-2 for Enhanced Rotator Cuff Repair

Zhonglian Wu,Jian Yang,Hui Chong,Xiaomei Dai,Haidi Sun,Junli Shi,Meijuan Yuan,Dianwei Liu,Mengbo Dang,Hang Yao,Wen-Yong Fei

Rotator cuff tear repair poses significant challenges due to the complex gradient interface structure. In the face of disease-related disruptions in the tendon-bone interface (TBI), the strategy of constructing a biomimetic scaffold is a promising avenue. A novel 3D-printed rotator cuff scaffold loaded adipose stem cells (ADSCs), bone morphogenetic protein-2 (BMP-2), and collagen type I (COL I). The efficiency of the slow-release BMP-2 design depended on the dopamine-hyaluronic acid (HAD) and BMP-2 reaction. The cumulative release of BMP-2 was 44.97% ± 5.45% at 4 weeks. The 3D-printed bilayer scaffold, incorporating COL I and BMP-2, effectively promoted the differentiation of ADSCs into osteogenic, tenogenic, and chondrogenic lineages in vitro. The combination of 3D-printed bioactive scaffolds and ADSCs demonstrated a superior repair effect on rotator cuff injuries in vivo. Therefore, these findings indicated that the 3D-printed biomimetic scaffold loaded with ADSCs and BMP-2 holds potential as a promising graft for TBI healing.

研究领域: 生物医学工程 · 组织工程 · 再生医学 · 骨科
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