Neutralization-Induced Self-Assembly of Cellulose Oligomers into Antibiofouling Crystalline Nanoribbon Networks in Complex Mixtures

Abstract

Molecular self-assembly in solutions is a powerful strategy for fabricating functional architectures. Various bio­(macro)­molecules have been used as self-assembly components. However, structural polysaccharides, such as cellulose and chitin, have rarely been a research focus for molecular self-assembly, even though their crystalline assemblies potentially have robust physicochemical properties. Herein, we demonstrated the neutralization-induced self-assembly of cellulose oligomers into antibiofouling crystalline nanoribbon networks to produce physically cross-linked hydrogels. The self-assembly proceeded even in versatile complex mixtures, such as serum-containing cell culture media, in a controlled manner for 3D cell culture. The cultured cells grew into cell aggregates (spheroids), which were simply collected through natural filtration due to the mechanically crushable property of the crystalline nanoribbons through water flow by pipetting. We will show the potential of cellulose oligomers for biocompatible, crystalline soft materials.

pH‐Triggered Self‐Assembly of Cellulose Oligomers with Gelatin into a Double‐Network Hydrogel

“…[27][28][29] Accordingly, we used a cellulose oligomer prepared using glucose primer as the raw material to compare the resultant DN hydrogels with previous studies. On the other hand, our previous report on the pH-triggered self-assembly of cellulose oligomers used shorter cellulose oligomers with an average DP of 7 as the raw material, [30] which was prepared using cellobiose primer ( Figure S1B, Supporting Information). [42,43] Therefore, we first investigated the pH-triggered self-assembly of the longer cellulose oligomer in the absence of gelatin.…”

“…The final conditions were 0.25−1.5% (w/v) cellulose oligomers in phosphate-buffered saline (PBS, pH 7.4) containing 0.137 m NaCl at 25 °C, which was in accordance with the previous pH-triggered self-assembly of the shorter cellulose oligomer. [30] Photographs of the resultant mixtures after 1 d of incubation are shown in Figure 2. Gelation occurred above 0.50% (w/v) of cellulose oligomers, even though the gels at 0.50% (w/v) were nonuniform macroscopically.…”

“…[26] The resultant multicomponent gels exhibited high stiffness, which was approximately three times the sum of the stiffnesses of the cellulose oligomer alone gels and the gelatin alone gels. Because cellulose oligomer assemblies have antifouling properties toward proteins, [30] the improvement in stiffness was considered to be based on the physical entanglement of the rigid cellulose oligomer networks and soft gelatin networks, indicating that the gels are so-called double-network (DN) hydrogels. [31,32] The biocompatibility of both components (i.e., cellulose oligomer [30] and gelatin [33] ) accompanied with the improved stiffness make the DN hydrogels promising as a biomaterial.…”

“…Because cellulose oligomer assemblies have antifouling properties toward proteins, [30] the improvement in stiffness was considered to be based on the physical entanglement of the rigid cellulose oligomer networks and soft gelatin networks, indicating that the gels are so-called double-network (DN) hydrogels. [31,32] The biocompatibility of both components (i.e., cellulose oligomer [30] and gelatin [33] ) accompanied with the improved stiffness make the DN hydrogels promising as a biomaterial. However, the process for preparing DN hydrogels needs to be refined for practical application, because it requires a special enzyme and a few days of reaction time, making it impossible to prepare the material on-demand.…”

“…Although the enzymatic synthesis and concurrent in situ self-assembly of cellulose oligomers has been the representative method for constructing cellulose oligomer-based selfassembled materials including gels, [27,28,[34][35][36][37][38][39][40][41] we recently demonstrated a novel alternative method: pH-triggered selfassembly. [30] In this method, as-prepared cellulose oligomer was dissolved in an alkaline NaOH solution at pH ≈ 13, followed by adding acidic HCl solution for the neutralization to trigger the self-assembly, leading to the formation of nanoribbon network hydrogels. The gelation occurred very quickly within 1 min to a few hours, depending on the conditions, such as cellulose oligomer concentration, temperature, and ionic strength.…”