Yu-cheng Zhang,Ya-qi Xue,Takayo Ogawa,Satoshi Wada,Jin-Ye Wang
Manufacturing biocompatible materials with higher-order structure has great significance because they can mimic the extracellular medium of the human organism and are a novel strategy for tissue regeneration. In this study, a device with stiffness-gradient characteristics based on two biocompatible materials, alginate with presolidification and photocurable acrylamide-containing supporting bath, was designed and constructed by the 3D printing technique. The presolidification can avoid rapid diffusion of alginate in aqueous solutions, improve mechanical properties without the introduction of heterogeneous gel precursor, and endow gradient stiffness by the controlled diffusion of calcium ions. Besides, a photocurable supporting bath was combined to manufacture a device with a dual-gradient structure by a 4-step procedure, including 3D printing, removal of the inner hydrogel, solidification of alginate, and curing of the supporting bath. A cylinder-like container was manufactured as the template, and the wall of the resultant container with two types of gradient structures showed parabola-like stiffness changes (open upward), resulting from calcium ion diffusion-controlled gradient solidification and alginate diffusion-controlled gradient photocuring. Moreover, the resultant device exhibited lower cytotoxicity to both adherent and suspension cells than containers manufactured with alginate. Because of the high water uptake of the photocured supporting bath, the removal of toxic metabolic products together with cell culture medium from the container leads to better cell compatibility. This diffusion-controlled device is also applicable to other additive manufacturers with biomedical significance.
Hu Yan,Yang Yang,Tian Fei,Xu Pingping,Du Rongcheng,Xia Xuehuan,Xu Shimei
It has attracted much attention to develop a gradient hydrogel for real mimic of the extracellular matrix. Despite simplicity and ease of electrophoresis preparation method, some drawbacks limit the application of the method including toxic organic crosslinker residual, specific ionic monomer types, as well as narrow gradient gaps. In this work, we successfully prepared gradiently crosslinked nonionic PNIPAm/Laponite nanocomposite (NC) hydrogels with controllable gradient structures by adjusting the intensity of the direct current electric field. The results showed that the stiffness, surface property and thermosensitivity of the hydrogel changed with gradient distributions of Laponite. The average stiffness gradients varied from 0.18 kPa/mm, 0.41 kPa/mm to 1.28 kPa/mm by simply adjusting the intensity of the direct current electric field from 0.13 V/mm, 0.20 V/mm to 0.27 V/mm accordingly. The stiffness reached in a range of 13.8∼33.0 kPa. The growth behaviors of human cervical cancer cells (HeLa cells) on the gradient NC hydrogel surface were discussed. Spreading and proliferation, as well as morphology of HeLa cells were closely related to the stiffness of the gradient NC hydrogels. This work develops a stiffness-controllable gradient NC hydrogel and opens up a new insight into the better understanding of cells behaviors in different tissues and organs in vivo .