Dodecyl glycoside intercalated organo-montmorillonite promoted biomimetic alginate/microcrystalline cellulose/nano-hydroxyapatite composite hydrogels for bone tissue engineering

To eliminate the brittleness of single ceramic materials and the poor mechanical properties, uncontrollable swelling and low biological activity of biological polysaccharides, thereby forming the tissue engineering scaffold capable of simulating natural bone tissue, alginate/microcrystalline cellulose/hydroxyapatite/organo-montmorillonite (ALG/MCC/HAP/OMMT) composite hydrogels were fabricated by in-situ crosslinking of alginate/microcrystalline cellulose mixed aqueous solution under the action of D-glucono-δ-lactone (GDL), using organo-montmorillonite (OMMT) as the filler and hydroxyapatite (HAP) as reinforcing agent and crosslinking agent. The experimental results indicated that non-ionic dodecyl polyglucoside (APG) intercalated into the interlayer of montmorillonite (MMT) through efficient wet ball milling technology to achieve the miscibility and effective dispersion of OMMT in alginate matrix. The presence of HAP and OMMT not only improved the mechanical properties, thermal stability, controllable swelling and degradability of the fabricated ALG/MCC/HAP/OMMT, but also enhanced their in vitro biomineralization performance. Furthermore, ALG/MCC/HAP/OMMT exhibited high encapsulation efficiency (EE) and loading rate (LR) for bovine serum albumin (BSA), and the BSA loading capacity increased with the increase of OMMT content. Meanwhile, ALG/MCC/HAP/OMMT also displayed good controlled release performance for BSA. Finally, the porous composite hydrogels formed by HAP, MCC and OMMT in alginate matrix presented good cell adhesion, proliferation and differentiation properties under the synergistic effect of their respective characteristics. To note, the implantation experiment in rabbit radius indicated that the ALG/MCC/HAP/OMMT composite hydrogels could effectively promote new bone formation in vivo, which was expected to be applied to clinical research. The ultimate goal of this study is to clarify the regulation rule of OMMT content on the physicochemical properties and structure of ALG/MCC/HAP/OMMT composite hydrogel, protein loading and release, cell compatibility and bone repair in vivo by investigating the interaction between components in composite hydrogel, so as to acquire unique alginate composite hydrogel based bone tissue engineering scaffolds.