The Synergistic Effect of Cyclic Tensile Force and Periodontal Ligament Cell-Laden Calcium Silicate/Gelatin Methacrylate Auxetic Hydrogel Scaffolds for Bone Regeneration. Cells The development of 3D printing technologies has allowed us to fabricate complex novel scaffolds for bone regeneration. In this study, we reported the incorporation of different concentrations of calcium silicate (CS) powder into fish gelatin methacrylate (FGelMa) for the fabrication of CS/FGelMa auxetic bio-scaffolds using 3D printing technology. Our results showed that CS could be successfully incorporated into FGelMa without influencing the original structural components of FGelMa. Furthermore, it conveyed that CS modifications both the mechanical properties and degradation rates of the scaffolds were improved in accordance with the concentrations of CS upon modifications of CS. In addition, the presence of CS enhanced the adhesion and proliferation of human periodontal ligament cells (hPDLs) cultured in the scaffold. Further osteogenic evaluation also confirmed that CS was able to enhance the osteogenic capabilities via activation of downstream intracellular factors such as pFAK/FAK and pERK/ERK. More interestingly, it was noted that the application of extrinsic biomechanical stimulation to the auxetic scaffolds further enhanced the proliferation and differentiation of hPDLs cells and secretion of osteogenic-related markers when compared to CS/FGelMa hydrogels without tensile stimulation. This prompted us to explore the related mechanism behind this interesting phenomenon. Subsequent studies showed that biomechanical stimulation works via YAP, which is a biomechanical cue. Taken together, our results showed that novel auxetic scaffolds could be fabricated by combining different aspects of science and technology, in order to improve the future chances of clinical applications for bone regeneration. 10.3390/cells11132069

Construction of tissue-customized hydrogels from cross-linkable materials for effective tissue regeneration. Journal of materials chemistry. B Hydrogels are prevalent scaffolds for tissue regeneration because of their hierarchical architectures along with outstanding biocompatibility and unique rheological and mechanical properties. For decades, researchers have found that many materials (natural, synthetic, or hybrid) can form hydrogels using different cross-linking strategies. Traditional strategies for fabricating hydrogels include physical, chemical, and enzymatical cross-linking methods. However, due to the diverse characteristics of different tissues/organs to be regenerated, tissue-customized hydrogels need to be developed through precisely controlled processes, making the manufacture of hydrogels reliant on novel cross-linking strategies. Thus, hybrid cross-linkable materials are proposed to tackle this challenge through hybrid cross-linking strategies. Here, different cross-linkable materials and their associated cross-linking strategies are summarized. From the perspective of the major characteristics of the target tissues/organs, we critically analyze how different cross-linking strategies are tailored to fit the regeneration of such tissues and organs. To further advance this field, more appropriate cross-linkable materials and cross-linking strategies should be investigated. In addition, some innovative technologies, such as 3D bioprinting, the internet of medical things (IoMT), and artificial intelligence (AI), are also proposed to improve the development of hydrogels for more efficient tissue regeneration. 10.1039/d1tb01935j