emerging as a potential alternative to these problems. The tissue engineering triad involves the effective integration of cells, scaffolds, and signals for the development of biological substitutes to restore, maintain, and replace injured tissues and organs. [2] The scaffold plays a substantial role in the field of tissue engineering, primarily by providing physical support (structures and substrates) for cells to attach and grow, subsequently resulting in tissue formation. [3] A variety of natural and synthetic biomaterials have been explored to develop tissue-engineered scaffolds. By incorporating exogenous growthstimulating signals, such as growth factors or small molecules, scaffolds can provide specific bioactivities, that is, biochemical signals required for cellular behaviors and tissue regeneration. [4] As biomaterials are essentially comprised of chemical molecules, they are capable of supplying inherent biochemical signals to guide and influence cells. For example, cells residing in tissue-engineered scaffolds can establish cell-biomaterial communication networks partially through biochemical signaling. The degradation products of various biodegradable biomaterials after implantation in vivo also provide specific biochemical signals to the cells in and around the Silk fibroin (SF) and sericin (SS), the two major proteins of silk, are attractive biomaterials with great potential in tissue engineering and regenerative medicine. However, their biochemical interactions with stem cells remain unclear. In this study, multiomics are employed to obtain a global view of the cellular processes and pathways of mesenchymal stem cells (MSCs) triggered by SF and SS to discern cell-biomaterial interactions at an in-depth, high-throughput molecular level. Integrated RNA sequencing and proteomic analysis confirm that SF and SS initiate widespread but distinct cellular responses and potentiate the paracrine functions of MSCs that regulate extracellular matrix deposition, angiogenesis, and immunomodulation through differentially activating the integrin/PI3K/Akt and glycolysis signaling pathways. These paracrine signals of MSCs stimulated by SF and SS effectively improve skin regeneration by regulating the behavior of multiple resident cells (fibroblasts, endothelial cells, and macrophages) in the skin wound microenvironment. Compared to SS, SF exhibits better immunomodulatory effects in vitro and in vivo, indicating its greater potential as a carrier material of MSCs for skin regeneration. This study provides comprehensive and reliable insights into the cellular interactions with SF and SS, enabling the future development of silk-based therapeutics for tissue engineering and stem cell therapy.
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.
The network-assisted full-duplex (NAFD) system realizes flexible duplex in the spatial domain within the same time-frequency resource. With the explosive growth of the number of users and remote antenna units (RAUs) under 6G scenario, the resource utilization of the system is lower. When the resource of users is selected by the RAUs to send or receive, collisions or congestion may occur due to mechanisms such as grant-free. Aiming at making better use of system resources, a load-aware dynamic mode selection scheme with NAFD scheme is proposed to improve the access efficiency and resource utility of the system. This paper first propose a centralized Q-learning algorithm which determines a clever strategy to approach the ultimate goal by itself and excels in environment dynamics. However, the size of the Q-table used in the centralized Q-learning algorithm for storage is huge. Further, a distributed multi-agent Q-learning algorithm is proposed which has a smaller size of Q-table and lower complexity to suit for actual scenarios. The simulation results showed that the proposed load-aware dynamic mode selection scheme can significantly improve resource utility and throughput performance than other traditional schemes.
Silk fibroin (SF) and sericin (SS), the two major proteins of silk, are attractive biomaterials that show great potential in regenerative medicine. However, their biochemical interactions with stem cells were not fully understood. Here, we employed multiomics to obtain a global view of the triggered cellular processes and pathways of MSCs by SF and SS. Integrated RNA-seq and proteomics revealed that SF and SS strongly enhanced the paracrine activity of MSCs through differentially activating integrin and glycolytic pathways, rather than directly regulating stem cell fate to initiate multiple but distinct biological processes in MSCs. Those specific paracrine signals of MSCs stimulated by SF and SS effectively promoted skin wound healing by influencing the behaviors of multiple resident cells in skin wound microenvironments. This study provides comprehensive and reliable insights into the cellular interactions with SF and SS, enabling future development of silk-based therapeutics for tissue engineering and stem cell therapy.
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