Natural Sulfated Polysaccharide Research Articles

Fucoidan suppresses proliferation and epithelial-mesenchymal transition process via Wnt/β-catenin signalling in hemangioma.

Hemangioma is a common benign tumour that usually occurs on the skin of the head and neck, particularly among infants. The current clinical treatment against hemangioma is surgery excision, however, application of drug is a safer and more economical therapy for children suffering from hemangioma. As a natural sulfated polysaccharide rich in brown algae, fucoidan is widely recognized for anti-tumour bioactivity and dosage safety in humans. This study aims to demonstrate the anti-tumour effect and underlying mechanism of fucoidan against hemangioma invivo and invitro. We investigated the effects of fucoidan by culturing hemangioma cells invitro and treating BALB/c mice bearing with hemangioma. At first, we measured the cell proliferation and migration ability through invitro experiments. Then, we tested the expression of epithelial-mesenchymal transition (EMT) and Wnt/β-catenin pathway-related biomarkers by western blot and qPCR. Furthermore, we applied β-catenin-specific inhibitor, XAV939, to determine whether fucoidan suppressed EMT via the Wnt/β-catenin pathway in hemangioma cells. Invivo experiments, we applied oral gavage of fucoidan to treat EOMA-bearing mice, along with evaluating the safety and efficacy of fucoidan. We found that fucoidan remarkably inhibits the proliferation and EMT ability of hemangioma cells, which is dependent on the Wnt/β-catenin pathway. These results suggest that fucoidan exhibits tumour inhibitory effect on aggressive hemangioma via regulating the Wnt/β-catenin signalling pathway both invitro and invivo, providing a new potent drug candidate for treating hemangioma.

Cystoseira myrica: from beach-cast seaweed to fucoidan with antioxidant and anticoagulant capacity

This study highlights the potential of the brown algae Cystoseira myrica, collected from raw beach seaweed wastes, as a reliable source of bioactive fucoidan. Fucoidans are natural bioactive sulfated polysaccharides that are gaining popularity worldwide due to their diverse biochemical composition, attractive physical properties, and functional pharmacological activities. The aim of this work is to valorize the beach-Accumulated brown algae C. myrica by fucoidan extraction and to investigate its anticoagulant and antioxidant activity. Fucoidan was extracted using several steps of papain digestion followed by cetyltrimethylammonium bromide (CTAB) precipitation and calcium chloride treatment to avoid the coextraction of other polysaccharides. Structural features of the extracted fucoidan were investigated by Fourier transform infrared spectroscopy (FT-IR), solid-state nuclear magnetic resonance (NMR) and high-resolution mass spectroscopy. Agarose gel electrophoresis was used to confirm the purity of the isolated fucoidan from C. myrica. Anticoagulant properties were studied in vitro by activated partial thromboplastin time (aPTT) and prothrombin time (PT) assays. Furthermore, the antioxidant activity was investigated by 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and Fe chelating ability. Our results indicate that the approach used was effective in extracting fucoidan with a yield of 3.07%, a high amount of sulfate (27.79%), and fucose was found to be the major monosaccharide component. The extracted fucoidan showed an interesting anticoagulant activity. It prolonged aPTT significantly at a concentration of 10 µg/ml and prolonged PT at high doses. This demonstrated that fucoidan from C. myrica may affect intrinsic pathways while having little impact on the extrinsic mechanism of coagulation. However, the extracted fucoidan significantly exhibited an interesting antioxidant capacity as shown by the higher ABTS radical scavenging activity and Ferrous ion-chelating effect. The current findings suggest that fucoidan isolated from C. myrica has unique structural, antioxidant and anticoagulant properties and offers innovative therapeutic possibilities.

Sulfated polysaccharides act as baits to interfere with the binding of the spike protein (SARS-CoV-2) to the ACE2 receptor and can be administered through food

Human civilization is experiencing a global crisis involving an unprecedented viral pandemic, with a high mortality rate, uncontrolled spread, and few effective drugs for treatment. Here, we critically evaluate how sulfated polysaccharides can be applied via foods to reduce the infectious process and increase the chances of an adequate immune response. The approach is directed to the infectious process by SARS-CoV-2 and protein S as a therapeutic focus. We discuss the antiviral activities of certain natural and specific sulfated polysaccharides that bind tightly to protein S. Finally, we identified that sulfated polysaccharides act as baits to interfere with the binding of the spike protein (SARS-CoV-2) to the ACE2 receptor and can be administered through food.

Fucoidan-ferulic acid nanoparticles alleviate cisplatin-induced acute kidney injury by inhibiting the cGAS-STING pathway

Fucoidan (FU) is a natural sulfated polysaccharide with certain biological activity and has been shown to be an excellent nano-delivery material. In this study, ferulic acid (FA)-loaded FU nanoparticles (FA/FU NPs) were prepared and their nephroprotective mechanism was investigated. With a particle size of 158.6 ± 4.5 nm, FA/FU NPs increased the antioxidant activity of FA in vitro, possibly related to the increased dispersity of FA. In vitro results demonstrated that FA/FU NPs significantly protected human renal proximal tubule (HK−2) cells from cisplatin-induced damage, possibly by suppressing cisplatin-induced DNA damage and activating the cGAS-STING pathway. Furthermore, in vivo experiments confirmed that FA/FU NPs protected mice from cisplatin-induced acute kidney injury (AKI). Mechanistic studies confirmed that FA/FU NPs exerted nephroprotective effects by reducing MDA activity and increasing GSH and SOD activity. Our results demonstrated the potential of FU for delivering poorly soluble drug FA and protecting against cisplatin-induced AKI.

Bio-inspired synthesis of amino acids modified sulfated cellulose nanofibrils into multivalent viral inhibitors via the Mannich reaction

Virus cross-infection via surfaces poses a serious threat to public health. Inspired by natural sulfated polysaccharides and antiviral peptides, we prepared multivalent virus blocking nanomaterials by introducing amino acids to sulfated cellulose nanofibrils (SCNFs) via the Mannich reaction. The antiviral activity of the resulting amino acid-modified sulfated nanocellulose was significantly improved. Specifically, 1 h treatment with arginine modified SCNFs at a concentration of 0.1 g/mL led to a complete inactivation of the phage-X174 (reduction by more than three orders of magnitude). Atomic force microscope showed that amino acid-modified sulfated nanofibrils can bind phage-X174 to form linear clusters, thus preventing the virus from infecting the host. When we coated wrapping paper and the inside of a face-mask with our amino acid-modified SCNFs, phage-X174 was completely deactivated on the coated surfaces, demonstrating the potential of our approach for use in the packaging and personal protective equipment industries. This work provides an environmentally friendly and cost-efficient approach to fabricating multivalent nanomaterials for antiviral applications.

Perspectives for the Use of Fucoidans in Clinical Oncology.

Fucoidans are natural sulfated polysaccharides that have a wide range of biological functions and are regarded as promising antitumor agents. The activity of various fucoidans and their derivatives has been demonstrated in vitro on tumor cells of different histogenesis and in experiments on mice with grafted tumors. However, these experimental models showed low levels of antitumor activity and clinical trials did not prove that this class of compounds could serve as antitumor drugs. Nevertheless, the anti-inflammatory, antiangiogenic, immunostimulating, and anticoagulant properties of fucoidans, as well as their ability to stimulate hematopoiesis during cytostatic-based antitumor therapy, suggest that effective fucoidan-based drugs could be designed for the supportive care and symptomatic therapy of cancer patients. The use of fucoidans in cancer patients after chemotherapy and radiation therapy might promote the rapid improvement of hematopoiesis, while their anti-inflammatory, immunomodulatory, and anticoagulant effects have the potential to improve the quality of life of patients with advanced cancer.

Cover Feature: Iron Oxide Nanoparticles Functionalized with Fucoidan: a Potential Theranostic Nanotool for Hepatocellular Carcinoma (ChemBioChem 16/2022)

Iron oxide nanoparticles (NPs) were functionalized with fucoidan, a natural sulfated polysaccharide. NP cellular uptake was quantified by magnetic measurement at various extracellular iron concentrations. Cell invasion and migration were reduced with NPs. Concomitantly, a high decrease of reactive oxygen species production related with a decrease of the matrix metalloproteinase-9 activity and an increase of its expression was observed. Proteomic analysis showed that some fucoidan regulated proteins appeared related to protein synthesis, N-glycan processing, and cellular stress. These results pave the way for USPIO-fucoidan-NPs as potential theranostic nanotools for hepatocellular carcinoma treatment. More information can be found in the Research Article by F. Geinguenaud et al.

Iron Oxide Nanoparticles Functionalized with Fucoidan: a Potential Theranostic Nanotool for Hepatocellular Carcinoma.

Fucoidan is a natural sulfated polysaccharide with a large range of biological activities including anticancer and anti-oxidation activities. Hepatocellular carcinoma is the fourth most common aggressive cancer type. The aim of this study was to investigate the bioactivity of free fucoidan versus its vectorization using nanoparticles (NPs) in human hepatoma cells, Huh-7. Iron oxide NPs were functionalized with fucoidan by a one-step surface complexation. NP cellular uptake was quantified by magnetic measurement at various extracellular iron concentrations. Cell invasion and migration were reduced with NPs while free fucoidan increases these events at low fucoidan concentration (≤0.5 μM). Concomitantly, a high decrease of reactive oxygen species production related with a decrease of the matrix metalloproteinase-9 activity and an increase of its expression was observed with NPs compared to free fucoidan. A proteomic analysis evidenced that some fucoidan regulated proteins appeared, which were related to protein synthesis, N-glycan processing, and cellular stress. To our knowledge, this is the first study which reveals such activity induced by fucoidan. These results pave the way for USPIO-fucoidan-NPs as potential theranostic nanotools for hepatocellular carcinoma treatment.

The anti-inflammatic activity of a sulfated polysaccharide Fucoidan in innate immune cells

Abstract Fucoidan is a series of natural sulfated polysaccharides derived from brown seaweeds and have reported to possess various biological activities such as anti-tumor, anti-virus, and immuno-modulatory effects. In previous study, we revealed that fucoidan derived from Cladosiphon okamuranus activated murine macrophage-like cell line RAW264 cooperatively with Zymosan, a Saccharomyces cerevisiae-derived β-glucan. On the other hand, several reports demonstrated that fucoidan inhibited lipopolysaccharide (LPS)-induced production of nitrogen oxide (NO) and inflammatory cytokines by RAW264 cells. Therefore, in this study, we investigated the potential of fucoidan derived from Undaria pinnatifida to regulate the excessive activation of RAW264 cells in response to overstimulation with pathogen components. RAW264 cells were inoculated at 20000 cells/well in 96-well culture plates, and after a recovery culture for 24 hr, the cells were treated with fucoidan with or without appropriate concentrations of each ligand for pattern recognition receptors (PRRs) including Toll-like receptors (TLRs). Whereas the production of NO was significantly enhanced with fucoidan alone, it was dose-dependently inhibited by fucoidan under stimulation with Pam3CSK4 (TLR1/TLR2 ligand), heat killed Listeria monocytogenes (HKLM, TLR2 ligand), LPS (TLR4 ligand), Pam2CGDPKHPKSF (FSL-1, TLR2/TLR6 ligand). These results suggested that fucoidan have beneficial ability to alleviate excessive inflammatory reaction during pathogenic infection and maintain suitable immune balance. Supported by Laboratory of Analytical Food Immunoscience belonging YM is a donated fund laboratory established in Faculty of Agriculture, Kyushu University by Ventuno Co., Ltd.

Antiviral Strategies Using Natural Source-Derived Sulfated Polysaccharides in the Light of the COVID-19 Pandemic and Major Human Pathogenic Viruses.

Only a mere fraction of the huge variety of human pathogenic viruses can be targeted by the currently available spectrum of antiviral drugs. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has highlighted the urgent need for molecules that can be deployed quickly to treat novel, developing or re-emerging viral infections. Sulfated polysaccharides are found on the surfaces of both the susceptible host cells and the majority of human viruses, and thus can play an important role during viral infection. Such polysaccharides widely occurring in natural sources, specifically those converted into sulfated varieties, have already proved to possess a high level and sometimes also broad-spectrum antiviral activity. This antiviral potency can be determined through multifold molecular pathways, which in many cases have low profiles of cytotoxicity. Consequently, several new polysaccharide-derived drugs are currently being investigated in clinical settings. We reviewed the present status of research on sulfated polysaccharide-based antiviral agents, their structural characteristics, structure–activity relationships, and the potential of clinical application. Furthermore, the molecular mechanisms of sulfated polysaccharides involved in viral infection or in antiviral activity, respectively, are discussed, together with a focus on the emerging methodology contributing to polysaccharide-based drug development.

Preparation, Antibacterial Activity, and Catalytic Application of Magnetic Graphene Oxide-Fucoidan in the Synthesis of 1,4-Dihydropyridines and Polyhydroquinolines.

Polymer‐coated magnetic nanoparticles are emerging as a useful tool for a variety of applications, including catalysis. In the present study, fucoidan‐coated magnetic graphene oxide was synthesized using a natural sulfated polysaccharide. The prepared BaFe12O19@GO@Fu (Fu=fucoidan, GO=graphene oxide) was characterized using Fourier‐transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy‐dispersive X‐ray (EDX) analysis, vibrating sample magnetometry (VSM), thermogravimetric analysis (TGA), Raman spectroscopy, and X‐ray diffraction (XRD). The catalytic proficiency of BaFe12O19@GO@Fu was investigated in the synthesis of 1,4‐dihydropyridine and polyhydroquinoline derivatives. Excellent turnover numbers (TON) and turnover frequencies (TOF) (6330 and 25320 h−1) testify to the high efficiency of the catalyst. Moreover, the antimicrobial activity of BaFe12O19@GO@Fu was evaluated against Escherichia coli (E. coli), and Staphylococcus aureus (S. aureus) through the Agar well diffusion method, indicating that BaFe12O19@GO@Fu has antibacterial activity against S. aureus.

Ulvan mediated VE cadherin antibody and REDV peptide co-modification to improve endothelialization potential of bioprosthetic heart valves

An aging population and a rapid increase in the incidence of degenerative valve diseases have led to greater use of bioprosthetic heart valves (BHVs). The durability of glutaraldehyde cross-linked bioprostheses currently available for clinical use is poor due to calcification, coagulation, and degradation. Decellularization can partially reduce calcification by removal of xenogenic cells, but can also lead to thrombosis, which can be addressed by further surface modification. The natural sulfated polysaccharide ulvan possesses antithrombotic and anti-inflammatory properties, and can behave as a heparinoid to immobilize proteins through their heparin binding sites. VE-cadherin antibody and the Arg-Glu-Asp-Val (REDV) peptide can facilitate selective endothelial cell attachment, adhesion and proliferation. In this study, we functionalized decellularized porcine pericardium (DPP) with ulvan, REDV, and VE-cadherin antibody (U-R-VE). Ulvan was covalently modified to act as a protective coating and spacer for VE-cadherin antibody, and to immobilize REDV. In in vitro tests, we found that functionalization significantly and selectively promoted adhesion and growth of endothelial cells while reducing platelet adhesion, inflammation, and in vitro calcification of DPPs. In an in vivo subdermal implantation model, U-R-VE modified DPP exhibited greater endothelialization potential and biocompatibility compared with unmodified pericardium. Thus, U-R-VE modification provides a promising solution to the problem of preparing BHVs with enhanced endothelialization potential.

Sulfonate Hydrogel-siRNA Conjugate Facilitates Osteogenic Differentiation of Mesenchymal Stem Cells by Controlled Gene Silencing and Activation of BMP Signaling.

Hydrogels have been widely used in bone tissue engineering due to their tunable characteristics that allow facile modifications with various biochemical properties to support cell growth and guide proper cell functions. Herein, we report a design of hydrogel-siRNA conjugate that facilitates osteogenesis via gene silencing and activation of bone morphogenetic protein (BMP) signaling. A sulfonate hydrogel is prepared by modifying chitosan with sulfoacetic acid to mimic a natural sulfated polysaccharide and to provide a hydrogel surface that enables BMP binding. Then, siRNA targeting noggin, an endogenous extracellular antagonist of BMP signaling, is covalently conjugated to the sulfonate hydrogel by visible blue light crosslinking. The sulfonate hydrogel-siRNA conjugate is efficient to bind BMPs and also successfully prolongs the release of siRNA for sustained noggin suppression, thereby resulting in significantly increased osteogenic differentiation. Lastly, demineralized bone matrix (DBM) is incorporated into the sulfonate hydrogel-siRNA conjugate, wherein the DBM incorporation induces noggin expression via a negative feedback mechanism that regulates BMP signaling in DBM. However, simultaneous delivery of siRNA downregulates noggin thus facilitating endogenous BMP activity and enhancing the osteogenic efficacy of DBM. These findings support a promising hydrogel RNA silencing platform for bone tissue engineering applications.

Seaweed Sulfated Polysaccharides against Respiratory Viral Infections.

Respiratory viral infections have been a leading cause of morbidity and mortality worldwide. Despite massive advancements in the virology field, no specific treatment exists for most respiratory viral infections. Approved therapies against respiratory viruses rely almost exclusively on synthetic drugs that have potential side effects, restricting their use. This review aims to present natural marine sulfated polysaccharides possessing promising antiviral activity against respiratory viruses that could be a safe alternative to synthetic broad-spectrum antiviral drugs. The antiviral properties of marine sulfated polysaccharides are presented according to their mechanism of action on different types and strains of respiratory viruses, and the potential limits of their use are discussed.

Regulatory mechanism of fucoidan-mix AG in intestinal mucosal immune cells

Abstract Fucoidan is a series of natural sulfated polysaccharides contained in brown sea algae, and their beneficial physiological activities such as anti-tumor, anti-virus and immune regulatory effects have been reported. In previous studies, we proved that fucoidans derived from Cladosiphon okamuranus (C. okamuranus) and Undaria pinnatifida effectively improved anti-tumor immunity and tumor vaccine efficiency in combination with an Agaricus blazei mycelium extract. It is thought that the fucoidan-agaricus mix (named fucoidan-mix AG) stimulate innate immune cells to activate intestinal and mucosal immune reaction, but actual target immune tissues and cells by fucoidan have not been evidenced yet. In this study, we investigated action mechanisms of fucoidan in regulation of mucosal immune activities. At first, immune cells were isolated from Payer’s patches, mesenteric lymph node (MLN) and intestinal epithelia of Balb/c mice, then stained with fluorophore-labeled fucoidan. As the results, it was revealed that fucoidan directly interact with lymphocytes besides dendritic cells and macrophages existing in these intestinal immune tissues. Furthermore, immune cells from Payer’s patches and MLN stimulated with fucoidan from C. okamuranus and fucoidan-mix AG produced more TNF-α, IL-12 and Th1 cytokine IFN-γ. The production of an immunosuppressive cytokine IL-10 also was augmented in the fucoidan-treated immune cells, which suggesting that fucoidan balanced immune system to prevent occurrence of excessive reaction. In addition, it was newly proved that fucoidan directly stimulated T lymphocytes to induce enhanced IFN-γ production.

A Comprehensive Review on Ulvan Based Hydrogel and Its Biomedical Applications.

Ulvan is a natural sulfated polysaccharide obtained from marine green algae composed of 3-sulfated rhamnoglucuronan as the main component. It has a unique chemical structure that rich of L-rhamnosa, D-glucuronic acid, and L-iduronic acid. Ulvan has a similar structure to glycosaminoglycans (GAGs) in mammals including chondroitin sulfate, dermatan sulfate, and heparan sulfate that has broad range applications for many years. Here, we provide an overview of ulvan based hydrogels for biomedical applications. Hydrogels are one of ulvan advances in polymer science for application in drug delivery, tissue engineering, and wound healing. This review presented an overview about functional information of ulvan based hydrogels and the promising potential in biomedicals collected from published papers in Scopus, PubMed, and Google Scholar. Other important aspects concerning properties, hydrogel-forming mechanisms, and ulvan based hydrogel developments were reported as well. As conclusion, ulvan showed interesting properties in forming hydrogels and promising advances in biomedical applications.

Biomimetic algal polysaccharide coated 3D nanofibrous scaffolds promote skin extracellular matrix formation

Development of functional biological substitutes for skin tissue engineering applications has observed several advancements over the past few decades. In this regard, intelligent extracellular matrix (ECM) mimetic scaffolds have recently evolved as a promising paradigm by presenting instructive cues directing cell-matrix communication, tissue remodeling and homeostasis. However, orchestring multitude attributes of skin ECM yet presents an intriguing challenge to be addressed. In the present work, we have developed an in vitro skin scaffold by coating a bio-mimetic ECM cue κ-carrageenan on electrospun nanofibers for the first time. κ-Carrageenan, a natural sulfated algal polysaccharide exhibits close similarity with native glucosaminoglycans (GAGs) of skin ECM. On the other hand, electrospun nanofibers resemble the 3D nano-topographic architecture of ECM. In the coated form, κ-carrageenan could provide the biochemical cues necessary for cellular functions on the nanofibrous scaffold, thereby mimicking the native 3D microenvironment of skin ECM. The nano-architecture of the electrospun matrix is retained in the fabricated scaffold even after coating with κ-carrageenan. The developed biomimetic scaffold significantly supplements adhesion, growth, infiltration, survival and proliferation of fibroblasts. Furthermore, enhanced gene expression and excessive secretion of collagen proteins by fibroblasts communicate a conducive skin ECM micro-environment formation on the algal polysaccharide coated nanofibrous scaffold. Taken together, these findings present a simple yet effective strategy for the fabrication of ECM mimetic scaffold for promising skin tissue engineering applications.

Development and Characterization of a Fucoidan-Based Drug Delivery System by Using Hydrophilic Anticancer Polysaccharides to Simultaneously Deliver Hydrophobic Anticancer Drugs.

Fucoidan, a natural sulfated polysaccharide, which can activate the immune response and lessen adverse effects, is expected to be an adjuvant agent in combination with chemotherapy. Using natural hydrophilic anticancer polysaccharides to simultaneously encapsulate hydrophobic anticancer drugs is feasible, and a reduced side effect can be achieved to amplify the therapeutic efficacy. In this study, a novel type of fucoidan-PLGA nanocarrier (FPN-DTX) was developed for the encapsulation of the hydrophobic anticancer drug, docetaxel (DTX), as a drug delivery system. From the comparison between FPN-DTX and the PLGA particles without fucoidan (PLGA-DTX), FPNs–DTX with fucoidan were highly stable with smaller sizes and dispersed well without aggregations in an aqueous environment. The drug loading and release can be further modified by modulating relative ratios of Fucoidan (Fu) to PLGA. The (FPN 3-DTX) nanoparticles with a 10:3 ratio of Fu:PLGA displayed uniform particle size with higher encapsulation efficiency than PLGA NPs and sustained drug release ability. The biocompatible fucoidan-PLGA nanoparticles displayed low cytotoxicity without drug loading after incubation with MDA-MB-231 triple-negative breast cancer cells. Despite lower cellular uptake than that of PLGA-DTX due to a higher degree of negative zeta potential and hydrophilicity, FPN 3-DTX effectively exerted better anticancer ability, so FPN 3-DTX can serve as a competent drug delivery system.

Ligand-aided 1H Nuclear Magnetic Resonance Spectroscopy for Non-destructive Estimation of Sulfate Content in Sulfated Saccharides.

Sulfated saccharides exhibit diverse physiological activities, but a lack of any convenient assay hinders their evaluation. Herein, an assay for the analysis of sulfated saccharides is described using 1H nuclear magnetic resonance (NMR) spectroscopy by employing ligands that can form ionic complexes with the sulfate groups. Based on the change in the chemical shift (Δδ) of the ligands by sulfated mono- to tetrasaccharide, imidazole was found to be a good ligand, showing the maximum Δδ; neutral saccharides do not show any change in the δ value. A marked and constant downfield δ value observed was changed dramatically at a molar ratio of >1:1 (imidazole:sulfated saccharides), allowing a sulfate content estimation based on the concentration of imidazole at the Δδ inflection point. By the proposed ligand-aided 1H NMR assay, the sulfate content of natural sulfated polysaccharide, fucoidan, was non-destructively estimated to be 2.1 mmol/g-fucoidan.

Affinity-selected polysaccharide for rhBMP-2-induced osteogenesis via BMP receptor activation

Bone morphogenetic protein-2 (BMP-2) is a key regulator of osteogenesis and always involved in bone regeneration and repair. However, supraphysiological BMP-2 doses are always associated with complications such as heterotopic ossification and inflammation, which leads to pain and impaired mobility. Polysaccharides have been widely used to bind BMP-2 and up-regulate its osteoinduction. Here, we developed a semi-synthetic polysaccharide, 2-N, 6-O-sulafted chitosan (26SCS), and compared its enhancement on recombinant human BMP-2 (rhBMP-2) induced osteogenesis with that of natural sulfated polysaccharide heparin and non-sulfated polysaccharide dextran. We found that both 26SCS and heparin amplified the signaling of rhBMP-2 on rat bone marrow stromal cells (RBMSCs) via enhancing the binding between rhBMP-2 and BMP-2 receptors (BMPRs) and activating the phosphorylation of Smad pathway, which lowered the effective dosage of rhBMP-2 on RBMSCs differentiation. By contrast, dextran had no effect on rhBMP-2-induced osteogenic differentiation. In addition, the pro-osteogenic potential of 26SCS and heparin combined with rhBMP-2 was confirmed in vivo using a mouse ectopic bone model. Micro-computed tomography and histological evaluation revealed more mature trabecular bone in the new ossified tissue with the treatment of 26SCS and low dose of rhBMP-2 than that with the treatment of high dose of rhBMP-2 alone. The addition of 26SCS did not activate osteoclast that led to bone resorption like heparin, but significantly promoted the angiogenesis. These findings suggested that 26SCS retained the advantages of heparin and amplified the regenerative capacity of rhBMP-2, which might provide a new strategy for growth factors correlated bone regeneration.