The Synergistic Effect of Cyclic Tensile Force and Periodontal Ligament Cell-Laden Calcium Silicate/Gelatin Methacrylate Auxetic Hydrogel Scaffolds for Bone Regeneration

Abstract

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.

Additive manufacturing of barium-doped calcium silicate/poly-ε-caprolactone scaffolds to activate CaSR and AKT signalling and osteogenic differentiation of mesenchymal stem cells

“…28 Additive manufacturing, also known as 3D printing, has made advances both in manufacturing and in regenerative medicine. 29–31 The ability to create custom structures with repeating and specific internal morphologies enables the development of scaffolds for the regeneration of tissues, such as skin, cartilage, or bone. 31 There have been several studies and products focused on 3D-printed PCL scaffolds for application in bone regeneration.…”

Distinct and overlapping functions of YAP and TAZ in tooth development and periodontal homeostasis

“…Currently, most research on YAP and TAZ focuses on indirectly targeting their activation by molecules such as blebbistatin, Cytochalasin D, Y-27, XAV939, and C3 toxin ( Yang et al, 2018 ; He et al, 2019 ; Xu et al, 2019 ; Wang Y. et al, 2020 ; Wei et al, 2020 ; Ehlinger et al, 2021 ; Hu et al, 2021 ). Verteporfin acts as a direct inhibitor of YAP ( Belgardt et al, 2020 ; Li et al, 2020 ; Lee et al, 2022 ). However, the majority of these interventions are still at the cellular or animal experimental stages.…”

Auxetic metamaterials for bone-implanted medical devices: Recent advances and new perspectives

“…Hence, stem cells could proliferate and differentiate more notably in NPR or auxetic scaffolds (Figure 10). Furthermore, (Lee Jr et al, 2022) developed an auxetic structure to find the effect of cyclic tensile force on bone regeneration of an auxetic scaffold. They utilized calcium silicate and gelatin methacrylate to fabricate scaffolds with the 3D printing method.…”