Oxidized sodium alginate (OSA) is selected as an appropriate material to be extensively applied in regenerative medicine, 3D-printed/composite scaffolds, and tissue engineering for its excellent physicochemical properties and biodegradability. However, few literatures have systematically investigated the structure and properties of the resultant OSA and the effect of the oxidation degree (OD) of alginate on its biodegradability and gelation ability. Herein, we used NaIO₄ as the oxidant to oxidize adjacent hydroxyl groups at the C-2 and C-3 positions on alginate uronic acid monomer to obtain OSA with various ODs. The structure and physicochemical properties of OSA were evaluated by Fourier transform infrared spectroscopy (FT-IR), ¹H nuclear magnetic resonance (¹H NMR), X-ray Photoelectron Spectroscopy (XPS), X-ray Diffraction (XRD), and thermogravimetric analysis (TGA). At the same time, gel permeation chromatography (GPC) and a rheometer were used to determine the hydrogel-forming ability and biodegradation performance of OSA. The results showed that the two adjacent hydroxyl groups of alginate uronic acid units were successfully oxidized to form the aldehyde groups; as the amount of NaIO₄ increased, the OD of OSA gradually increased, the molecular weight decreased, the gelation ability continued to weaken, and degradation performance obviously rose. It is shown that OSA with various ODs could be prepared by regulating the molar ratio of NaIO₄ and sodium alginate (SA), which could greatly broaden the application of OSA-based hydrogel in tissue engineering, controlled drug release, 3D printing, and the biomedical field.

It is common knowledge that pure alginate hydrogel is more likely to have weak mechanical strength, a lack of cell recognition sites, extensive swelling and uncontrolled degradation, and thus be unable to satisfy the demands of the ideal scaffold. To address these problems, we attempted to fabricate alginate/bacterial cellulose nanocrystals-chitosan-gelatin (Alg/BCNs-CS-GT) composite scaffolds using the combined method involving the incorporation of BCNs in the alginate matrix, internal gelation through the hydroxyapatite-d-glucono-δ-lactone (HAP-GDL) complex, and layer-by-layer (LBL) electrostatic assembly of polyelectrolytes. Meanwhile, the effect of various contents of BCNs on the scaffold morphology, porosity, mechanical properties, and swelling and degradation behavior was investigated. The experimental results showed that the fabricated Alg/BCNs-CS-GT composite scaffolds exhibited regular 3D morphologies and well-developed pore structures. With the increase in BCNs content, the pore size of Alg/BCNs-CS-GT composite scaffolds was gradually reduced from 200 μm to 70 μm. Furthermore, BCNs were fully embedded in the alginate matrix through the intermolecular hydrogen bond with alginate. Moreover, the addition of BCNs could effectively control the swelling and biodegradation of the Alg/BCNs-CS-GT composite scaffolds. Furthermore, the in vitro cytotoxicity studies indicated that the porous fiber network of BCNs could fully mimic the extracellular matrix structure, which promoted the adhesion and spreading of MG63 cells and MC3T3-E1 cells on the Alg/BCNs-CS-GT composite scaffolds. In addition, these cells could grow in the 3D-porous structure of composite scaffolds, which exhibited good proliferative viability. Based on the effect of BCNs on the cytocompatibility of composite scaffolds, the optimum BCNs content for the Alg/BCNs-CS-GT composite scaffolds was 0.2% (w/v). On the basis of good merits, such as regular 3D morphology, well-developed pore structure, controlled swelling and biodegradation behavior, and good cytocompatibility, the Alg/BCNs-CS-GT composite scaffolds may exhibit great potential as the ideal scaffold in the bone tissue engineering field.

To extend the alginate applicability for the sustained release of hydrophobic medicine in drug delivery systems, the alkyl alginate ester derivative (AAD), including hexyl alginate ester derivative (HAD), octyl alginate ester derivative (OAD), decyl alginate ester derivative (DAD), and lauryl alginate ester derivative (LAD), were synthesized using the alkyl bromides with different lengths of carbon chain as the hydrophobic modifiers under homogeneous conditions via the bimolecular nucleophilic substitution (S_N2) reaction. Experimental results revealed that the successful grafting of the hydrophobic alkyl groups onto the alginate molecular backbone via the S_N2 reaction had weakened and destroyed the intramolecular hydrogen bonds, thus enhancing the molecular flexibility of the alginate, which endowed the AAD with a good amphiphilic property and a critical aggregation concentration (CAC) of 0.48~0.0068 g/L. Therefore, the resultant AAD could form stable spherical self-aggregated micelles with the average hydrodynamic diameter of 285.3~180.5 nm and zeta potential at approximately −44.8~−34.4 mV due to the intra or intermolecular hydrophobic associations. With the increase of the carbon chain length of the hydrophobic side groups, the AAD was more prone to self-aggregation, and therefore was able to achieve the loading and sustained release of hydrophobic ibuprofen. Additionally, the swelling and degradation of AAD microcapsules and the diffusion of the loaded drug jointly controlled the release rate of ibuprofen. Meanwhile, the AAD also displayed low cytotoxicity to the murine macrophage RAW264.7 cells. Thanks to the good amphiphilic property, colloidal interface activity, hydrophobic drug-loading performance, and cytocompatibility, the synthesized AAD exhibited a great potential for the development of hydrophobic pharmaceutical formulations.