Dual-Cross-linked Liquid Crystal Hydrogels with Controllable Viscoelasticity for Regulating Cell Behaviors

Abstract

The liquid crystal properties and viscoelasticity of the natural bone extracellular matrix (ECM) play a decisive role in guiding cell behavior, conducting cell signals, and regulating mineralization. Here, we develop a facile approach for preparing a novel polysaccharide hydrogel with liquid crystal properties and viscoelasticity similar to those of natural bone ECM. First, a series of chitin whisker/chitosan (CHW/CS) hydrogels were prepared by chemical cross-linking with genipin, in which CHW can self-assemble to form cholesteric liquid crystals under ultrasonic treatment and CS chains can enter into the gaps between the helical layers of the CHW cholesteric liquid crystal phase to endow morphological stability and good mechanical properties. Subsequently, the obtained chemically cross-linked liquid crystal hydrogels were immersed into the desired concentration of the NaCl solution to form physical cross-linking. Due to the Hofmeister effect, the as-prepared dual-cross-linked liquid crystal hydrogels showed an enhanced modulus, viscoelasticity similar to that of natural ECM with relatively fast stress relaxation behavior, and fold surface morphology. Compared to both CHW/CS hydrogels without liquid crystal properties and CHW/CS liquid crystal hydrogels without further physical cross-linking, the dual-cross-linked CHW/CS liquid crystal hydrogels are more favorable for the adhesion, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells. This approach could inspire the design of hydrogels mimicking the liquid crystal properties and viscoelasticity of natural bone ECM for bone repair.

Bone ECM-like 3D Printing Scaffold with Liquid Crystalline and Viscoelastic Microenvironment for Bone Regeneration

“…In light of the formation conditions of HCHW liquid crystal, it is necessary to find out whether the introduction of a covalent cross-linking network will destroy the helical arrangement of HCHW. In fact, according to our previous work, this helical arrangement is extremely dependent on the ratio of CS to HCHW, and the excess of CS will destroy this chiral structure. As presented in the polarizing microscope (POM) images of Figure b, both the liquid crystal suspension and CG maintained the liquid crystal state and colorful texture well.…”

“…For the CG, its osteogenic activity is considered to be related to the liquid crystal topology and viscoelasticity. On one hand, the liquid crystal topology of CG could act as the mineralization template to induce the deposition of calcium phosphate salt (Figure g). , On the other hand, as illustrated in Figure h, the mechanical cues of viscoelastic network can be transmitted into BMSCs through integrins, and then activate the Cdc42-mediated Wnt/β-catenin pathway to promote the expression of osteogenic factors. , The DFO-mediated signaling pathway is closely related to the chelation of iron ions by DFO. ,, The iron-deficient environment will inhibit the activity of intracellular prolyl hydroxylases (PHDs), which further inhibits the degradation of HIF-1α. As a result, the continuous accumulation of HIF-1α in cells leads to the activation of the HIF-1α signaling pathway to promote the expression of osteogenesis-related genes.…”

“…On one hand, the liquid crystal topology of CG could act as the mineralization template to induce the deposition of calcium phosphate salt (Figure 6g). 12,19 On the other hand, as illustrated in Figure 6h, the mechanical cues of viscoelastic network can be transmitted into BMSCs through integrins, and then activate the Cdc42-mediated Wnt/βcatenin pathway to promote the expression of osteogenic factors. 47,48 The DFO-mediated signaling pathway is closely related to the chelation of iron ions by DFO.…”

The Diamond Concept Enigma: Recent Trends of Its Implementation in Cross-linked Chitosan-Based Scaffolds for Bone Tissue Engineering

“…Thus, it is arguably a necessary methodology with regards to claiming successful differentiation potential. This assay is sometimes complemented with other techniques such as qPCR, which serves to assess gene 65,66,70,[75][76][77][78]80,82,[86][87][88][89][90]99,105,107,113,120,124,130,131,138,140,145,152,153,162,167,169,170…”

Interface Barrier Layers to Suppress Side Redox Reactions of High‐Voltage Hydrogel Iontronics

“…Therefore, hydrogels have been developed and utilized in a variety of medical applications, including tissue scaffolds, [9] drug delivery, [10] and wound dressings. [11,12] Over the past few years, the assortment of multifunctional soft iontronic devices based on hydrogel/ionogel electrodes have been demonstrated, such as electronic skins, [13][14][15][16] artificial muscles and axons, [17][18][19] AC luminous devices, [20][21][22] liquid crystal devices, [23,24] flexible ionic diodes, [25,26] and triboelectric nanogenerators (TENG). [27][28][29] Nevertheless, the breakdown of hydrogel iontronic devices under electrified conditions should be sufficiently considered.…”