Fucoidan-Coated Silica Nanoparticles Promote the Differentiation of Human Mesenchymal Stem Cells into the Osteogenic Lineage

Abstract

Silica nanoparticles (SiNPs) are widely used in biomedical applications, such as cancer therapy/diagnosis or tissue engineering and regenerative medicine. Herein, we synthesized SiNPs and modified them with sulfonic acid groups (by organosilylation followed by oxidation) or a sulfated polysaccharide (i.e., fucoidan, a seaweed biopolymer, by using electrostatic surface immobilization) due to the known capacity of the sulfonic/sulfate moieties to stabilize proteins and promote stem cell differentiation toward the osteogenic lineage. The developed pristine and functionalized nanoparticles were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS), showing the monodisperse size distribution (between 360 and 450 nm) and the success of the coating/functionalization with fucoidan or sulfonic groups. The developed SiNPs (at a concentration of 50 μg/mL) were assessed through their contact with SaOs2 cells evidencing their cytocompatibility. Furthermore, the osteogenic differentiation of bmMSCs was evaluated by the quantification of ALP activity, as well as the expression profile of osteogenic-related genes, such as Runx2, ALP, and OP. We found that the coating of the SiNPs with fucoidan induced the osteogenic differentiation of bmMSCs, being an effective mediator of bone regeneration.

Effects of Different Surface Functionalizations of Silica Nanoparticles on Mesenchymal Stem Cells

“…Small molecules or forced expression of reprogramming factors are commonly used to generate human-induced pluripotent cells from somatic cells and differentiate them into the desired cell types. − A few studies have recently reported the successful use of silica nanoparticles to modulate cell differentiation. For example, the induction of MSCs to specific cell types such as osteocytes , and adipocytes was achieved using specific silica nanoparticles. Similarly, silica nanoparticles have also been used to inhibit the differentiation of MSCs to adipocytes.…”

“…This is in line with studies related to the important role of phosphate in the development of mineralized tissues such as initial bone deposition and enhancement of the early stages of osteoblastic differentiation. − Nevertheless, the majority of current differentiation induction approaches used a Matrigel-based scaffold material or a culture dish coated with specific biomaterials to modulate cell signaling externally, and only a limited number of studies used functionalized nanoparticles to modulate cell signaling intracellularly and promote stem cell differentiation. For example, silica nanoparticles modified with other chemical functional groups such as fucoidan, calcium phosphate, and strontium have also been successfully used to induce osteogenic stem cell differentiation. Therefore, silica nanoparticles functionalized with small chemical moieties such as phosphate groups can potentially be used for facilitating osteogenesis and accelerating recovery in bone fracture patients.…”

“…46−48 A few studies have recently reported the successful use of silica nanoparticles to modulate cell differentiation. For example, the induction of MSCs to specific cell types such as osteocytes 49,50 and adipocytes 51 was achieved using specific silica nanoparticles. Similarly, silica nanoparticles have also been used to inhibit the differentiation of MSCs to adipocytes.…”