K-Carrageenan Stimulates Pre-Osteoblast Proliferation and Osteogenic Differentiation: A Potential Factor for the Promotion of Bone Regeneration?

Abstract

Current cell-based bone tissue regeneration strategies cannot cover large bone defects. K-carrageenan is a highly hydrophilic and biocompatible seaweed-derived sulfated polysaccharide, that has been proposed as a promising candidate for tissue engineering applications. Whether κ-carrageenan can be used to enhance bone regeneration is still unclear. In this study, we aimed to investigate whether κ-carrageenan has osteogenic potential by testing its effect on pre-osteoblast proliferation and osteogenic differentiation in vitro. Treatment with κ-carrageenan (0.5 and 2 mg/mL) increased both MC3T3-E1 pre-osteoblast adhesion and spreading at 1 h. K-carrageenan (0.125–2 mg/mL) dose-dependently increased pre-osteoblast proliferation and metabolic activity, with a maximum effect at 2 mg/mL at day three. K-carrageenan (0.5 and 2 mg/mL) increased osteogenic differentiation, as shown by enhanced alkaline phosphatase activity (1.8-fold increase at 2 mg/mL) at day four, and matrix mineralization (6.2-fold increase at 2 mg/mL) at day 21. K-carrageenan enhanced osteogenic gene expression (Opn, Dmp1, and Mepe) at day 14 and 21. In conclusion, κ-carrageenan promoted MC3T3-E1 pre-osteoblast adhesion and spreading, metabolic activity, proliferation, and osteogenic differentiation, suggesting that κ-carrageenan is a potential osteogenic inductive factor for clinical application to enhance bone regeneration.

Sulfated carboxymethyl cellulose and carboxymethyl κ-carrageenan immobilization on 3D-printed poly-ε-caprolactone scaffolds differentially promote pre-osteoblast proliferation and osteogenic activity

“…Moreover, it has been shown that sulfated polymer grafting onto a scaffold surface increases the secretion of fibronectin and collagen by osteoblasts (Pavon-Djavid et al, 2007). The Frontiers in Bioengineering and Biotechnology frontiersin.org sulfated polysaccharide ĸ-Car promotes paxillin protein expression by pre-osteoblasts (Cao et al, 2021). Protein adsorption on a scaffold surface promotes cell adhesion, proliferation, and osteogenic differentiation (Gandavarapu et al, 2013).…”

“…Glycosaminoglycan (GAG)-like anionic polysaccharides are also widely used for biomaterial functionalization, because of their ability to facilitate cell adhesion, proliferation, and differentiation (Malliappan et al, 2022). Among several kinds of anionic polysaccharides, carboxymethyl cellulose (CMC; a plant-based carboxymethylated polysaccharide) (Seddiqi et al, 2021), and κcarrageenan (a seaweed-derived sulfated polysaccharide) (Cao et al, 2021) have attracted attention for tissue engineering applications. The ease of chemical functionalization, hydrophilicity, favorable mechanical properties, and biocompatibility make CMC and κcarrageenan interesting for tissue engineering applications (Cao et al, 2021;Zennifer et al, 2021).…”

“…Among several kinds of anionic polysaccharides, carboxymethyl cellulose (CMC; a plant-based carboxymethylated polysaccharide) (Seddiqi et al, 2021), and κcarrageenan (a seaweed-derived sulfated polysaccharide) (Cao et al, 2021) have attracted attention for tissue engineering applications. The ease of chemical functionalization, hydrophilicity, favorable mechanical properties, and biocompatibility make CMC and κcarrageenan interesting for tissue engineering applications (Cao et al, 2021;Zennifer et al, 2021). The chemical modification of anionic polysaccharides by sulfate and carboxymethyl groups is an important route to enhance their bioactivity (Palhares et al, 2021).…”

Notoginsenoside R1 Promotes Migration, Adhesin, Spreading, and Osteogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stromal Cells

“…The attached number of cells was considered to represent cell adhesion. The surface area of cells was considered to quantitatively represent cell spreading [ 74 , 75 ].…”

Carrageenan-Based Compounds as Wound Healing Materials

“…In addition to wound healing applications, K-carrageenan presents remarkable results in the field of regenerative medicine [ 124 ]. Thus, K-CG has been reported to have osteogenic potential because it induced the metabolic activity of pre-osteoblast cells [ 125 ]. Silk fibroin/K-CG electrospun nanofibers showed great osteogenic properties [ 126 ].…”