Alginate/layered double hydroxide composite aerogels for 3D culture and scaffolding

Abstract

Alginate (Alg) hydrogels are widely investigated as scaffolds for 3D cell culture despite their inherent limitations in supporting cell adhesion, proliferation, and differentiation. Incorporating inorganic fillers, such as layered double hydroxides (LDH), is expected to enhance both the mechanical and biological properties of these materials. In this study, LDH intercalated with osteoinductive small molecules (OSM) were synthesized and incorporated into highly porous Alg aerogels. These aerogels exhibited rapid hydration while maintaining their overall shape and size, with significant morphological changes occurring only after 5–10 weeks. This rapid rehydration .facilitated an immediate and homogeneous initial seeding of MC3T3-E1 mouse preosteoblasts throughout the scaffold volume upon rehydration. The resulting scaffolds maintained structural integrity for over five weeks—an effect further enhanced by the LDH particles. Nevertheless, the intercalated anions were also a decisive factor, with glycerophosphate-loaded LDH leading to a decrease in long-term structural integrity. Furthermore, the scaffolds served as templates for the deposition of apatite-like materials in simulated body fluid media. While all Alg scaffolds supported cell growth, the LDH-containing composites showed improved proliferation and differentiation, which were modulated by the specific intercalated anions. Although cell proliferation was concentrated primarily near the scaffold surface in contact with the growth medium, the structural stability and initial cell distribution indicate that these aerogels are promising precursors for 3D cell cultures and bone tissue engineering applications.