CHEMICAL ENGINEERING JOURNAL
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2026
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IF 12.5
Huanhuan Liu,Xiaolei Fan,Jingyan Huang,ZiXu Wang,Runli Li,Ruoyu Li,Bo Yang,Yan Wang
Dentin hypersensitivity is a globally oral dilemma arising from the exposure of dentinal tubules (DTs), which elicits discomfort upon external stimulation. Due to the complex dentin structure and oral environment, developing a multifunctional repair strategy that combines dentin remineralization, antibacterial properties, and DT occlusion remains highly challenging. Herein, we propose a biomimetic remineralization approach utilizing glycosaminoglycan chondroitin sulfate (CS) to mimic the bioactivity of proteoglycans (GAGs) for modifying collagen fibrils, in conjunction with a zwitterionic poly(carboxybetaine acrylamide) (PCBAA) to stabilize amorphous calcium phosphate (ACP), CS modification not only increases the negative charge density on the collagen but also provides additional nucleation sites, facilitating the binding of calcium phosphate precursors and thereby promoting collagen mineralization. Both in vitro and in vivo experiments demonstrate that the CS-based biomimetic mineralization strategy achieves dense occlusion of DTs and effective remineralization of demineralized dentin. The remineralized dentin exhibits significant antibacterial activity against cariogenic bacteria (e.g., Streptococcus mutans and Lactobacillus acidophilus ), and its mechanical properties can be restored to level comparable to that of sound dentin. Thus, this strategy integrates three key functions, dentin matrix remineralization, effective tubular occlusion, and antibacterial surface modification, offering substantial clinical potential for the effective treatment of dentin hypersensitivity.
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CARBOHYDRATE POLYMERS
·
2026
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IF 13.2
Haofeng Qiu,Jingfang Zheng,Zheyu Yao,Ximing Cai,Gaoke Pan,Xufeng Mao,Xin Zhao,Lei Shao,Dangsheng Xiong,Rong Wang,Yi Zhang
Cartilage degradation after joint injury often leads to post-traumatic osteoarthritis, a process accompanied by a drop in synovial pH. Traditional dynamically crosslinked hydrogels overlook how their mechanical and tribological properties change in such acidic, inflammatory environments. Here, we report an arthritis-responsive, injectable hydrogel designed to both regenerate articular cartilage and inhibit its further degradation. The hydrogel is formed via Schiff base chemistry between aldehyde groups of oxidized hyaluronic acid (OHA) and amino groups of adipic acid dihydrazide-grafted chondroitin sulfate (Chs-ADH) and carboxyethyl chitosan (CEC). Under neutral pH, the imine bonds remain stable, allowing precise defect filling and minimizing stress-induced debris; under acidic conditions, their reversible nature enhances lubrication and resists wear. The hydrogel formulation was optimized using molecular dynamics simulations to achieve excellent injectability, shear-thinning behavior, and low friction without impeding normal joint motion. In vitro , the hydrogel exhibited outstanding biocompatibility and stimulated cell migration. In vivo , it accelerated cartilage repair, prevented cartilage degradation, and restored the lubrication of newly formed tissue to levels comparable with healthy cartilage. Together, these findings demonstrate that the pH-sensitive hydrogel is a promising candidate for effective cartilage repair and prevention of cartilage degradation.
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BIORESOURCE TECHNOLOGY
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2026
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IF 8.2
Weiwei Meng,Mengjian Gao,Lulu Li,Liming Liu,Xiaomin Li,Wanqing Wei,Jing Wu
Osteoarthritis remains a global health problem and chondroitin sulfate C (CSC) is effective to treat arthritis. The biosynthesis of CSC offers a sustainable and promising alternative to conventional extraction from animal tissues. However, the scarcity of chondroitin-6-O-sulfotransferases and their low catalytic performance have severely hindered the large-scale biosynthesis of CSC. To overcome these limitations, a novel chondroitin-6-O-sulfotransferase from Rattus norvegicus ( Rn CHST3) was identified via gene fishing, which demonstrates regioselectivity in transferring a sulfate group from 3′-phosphoadenosine-5′-phosphosulfate (PAPS) to the 6-position of chondroitin. Subsequent optimization of expression conditions and truncation of the N -terminal region enhanced the sulfation rate from 4.6% to 11.5%. For the first time, the regioselective mechanism of Rn CHST3 was elucidated through molecular dynamics (MD) simulations and site-directed mutagenesis. A mechanism-guided rational design led to the development of mutant M5, which increased the sulfation rate to 46.2%. Furthermore, a novel “physical sieve”-guided PROSS design was developed to improve kinetic thermostability, resulting in mutant M7. This variant exhibited an extended half-life from 9.4 h to 12.3 h and achieved a sulfation rate to 74.5%. Finally, a whole-cell catalytic system was constructed for CSC production, reaching a sulfation rate of 86.4% and a titer of 12.9 g·L −1 -the highest level reported to date. This study lays a solid foundation for the industrial biosynthesis of CSC.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2026
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IF 6
Yawen Yao,Min Zhang,Sai Xu,Guoping Wu,Xinwang Meng,Juan Li,Hua Yu
A chondroitin sulfate-functionalized GSH-responsive lipid-nanoparticle (CSD@DNLP) was developed for co-delivering doxorubicin (DOX) and nifuroxazide (NIF) in metastatic melanoma treatment. • Chondroitin sulfate-functionalization improved cellular uptake through targeting CD44-receptors and enhanced drugs release in tumor-mimic environment. • Synergistic effects were observed in tumor growth inhibition and metastasis repression through NIF-mediated STAT3 phosphorylation blockade and DOX-induced DNA damage. • CSD@DNLP demonstrated a promising strategy in metastatic melanoma. Tumor metastasis results in high mortality rate in patients with advanced melanoma. The hyperphosphorylation of signal transducer and activator of transcription 3 (STAT3) is closely associated with the proliferation and metastasis of melanoma. Here, we proposed a lipid-nanoparticle (CSD@DNLP) derived from the chondroitin sulfate (CS)-conjugated deoxycholic acid (DOCA) polymer (CS-ss-DOCA, CSD) for the co-delivery of doxorubicin (DOX) and STAT3 inhibitor nifuroxazide (NIF) in metastatic melanoma treatment. The superior affinity between CS and overexpressed CD44 receptors in B16F10 cells resulted in 3.3-fold enhancement of cellular uptake compared to free DOX. CSD@DNLP maintained structural stability in physiological conditions, while achieving 75.15% cumulative release within 48 h under a tumor-mimic concentration of glutathione (GSH, 20 mM). Synergistic effects were observed through NIF-mediated STAT3 phosphorylation blockade and DOX-induced DNA damage, resulting in 3.2-fold enhancement in apoptotic cells versus free drugs. In lung metastasis mice, CSD@DNLP suppressed metastatic nodule formation (36% of free DOX + NIF) via dual downregulation of matrix metalloproteinases-2 (MMP-2) and metalloproteinases-2 (MMP-9). This CS-functionalized GSH-responsive lipid-nanoparticle demonstrates a promising strategy in metastatic melanoma. Download: Download high-res image (162KB) Download: Download full-size image
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BIOMATERIALS
·
2025
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IF 12.9
Lamei Liu,Min Zhang,Yan Zhou,Lin He,Mingjian Chen,Yuchen Wu,Guanyu Yin,Hui He,Lanlin Qi,Bin Zhang,Xiaoxiao He,Kemin Wang
Osteoarthritis (OA) is a complex and multifactorial joint disorder. Currently, there are few therapies to slow the progression of OA. Combining symptomatic slow-acting drugs and reactive oxygen species (ROS) scavenging reagents in the inflamed joint shows a promising therapeutic approach for OA. Nonetheless, the short residence time of free drugs in the joint cavity hinders their further application. Herein, an injectable composite of hydrogel and chondroitin sulfate@resveratrol liposome package (Gel/Lip@Res + Chs) was developed to improve drug residency ability and enable the simultaneous delivery of hydrophilic Chs and hydrophobic Res in the joint cavity. This injectable hydrogel, based on phenylboronic acid modified hyaluronic acid (HAPBA) and polyvinyl alcohol (PVA), provided ROS-responsive decomposition property and sustained drug release behavior, thereby effectively scavenging ROS, promoting macrophage repolarization, and decreasing the expression of inflammatory mediators and matrix-degrading enzymes in vitro . As a proof of concept, the in vivo therapeutic efficacy of Gel/Lip@Res + Chs was further examined in both monoiodoacetic acid (MIA)-induced and surgical anterior cruciate ligament transection (ACLT)-induced OA mouse models. Benefiting from the extended residence time of loaded drugs in the joint cavity, the Gel/Lip@Res + Chs treatment could effectively suppress cartilage degeneration and increase the synthesis of the cartilage matrix, thus slowing the advancement of OA. The present study provides a reference for improving drug retention and holds great potential for treating OA-related diseases.
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Biomaterials Science
·
2023
·Vol. 11
·期 10
·3629-3644
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IF 6.6
Huitong Luo,Zetao Wang,Zhichao He,Zemin Ling,Hao Wang,Jiayi Zhu,Jingjun Nie,Dafu Chen,Qi Feng,Xiaodong Cao
Overactive inflammatory cascade accompanied by oxidative stress in the nucleus pulposus exacerbates intervertebral disc degeneration (IVDD). Hydrogels have been demonstrated to be promising in treating IVDD, yet they remain less efficacious in the case of anti-inflammation associated with antioxidation. In this study, we designed an injectable self-antioxidant hydrogel (HA/CS) with enhanced inflammation inhibitory performance for delivering chondroitin sulfate (CS) with well-documented anti-inflammatory property to treat IVDD. The hydrogel was rapidly formed via dynamic boronate ester bonding between furan/phenylboronic acid and furan/dopamine-modified hyaluronic acid (HA), and mechanically enhanced by Diels–Alder reaction-induced secondary crosslinking, partial dopamine groups of which contribute to grafting phenylboronic acid-modified CS (CS-PBA). This hydrogel exhibits favorable injectability, mechanical property, and pH-responsive delivery behavior. The dopamine moiety endows the hydrogel with efficient antioxidative property. By sustained delivery of CS, the HA/CS hydrogel is well competent to inhibit inflammatory cytokine expression and maintain anabolic/catabolic balance in an inflammation-simulated environment. Most importantly, the HA/CS hydrogel significantly ameliorates degeneration in a puncture-induced IVDD rat model. The self-antioxidant HA/CS hydrogel designed in this work may serve as a novel and promising therapeutic platform for IVDD.
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CARBOHYDRATE POLYMERS
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2022
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IF 10.723
Ronghua Yin,Ying Pan,Ying Cai,Fan Yang,Na Gao,Dilihumaer Ruzemaimaiti,Jinhua Zhao
Fucosylated chondroitin sulfate (FCS) from sea cucumber Ludwigothurea grisea (FCS Lg ) is the first one that reported to bear the di-fucosyl branches. Here we deciphered it by analyzing the physicochemical properties and its derivatives. Oligosaccharides prepared by selective cleavage of glycosidic linkages presented the mono-fucose and heterodisaccharide branches in FCS Lg . The disaccharide branch was determined as d -GalNAc R1 -(α1,2)- l -Fuc R2 rather than the di-fucosyl branch, where R1 was 4-mono-O- or 4,6-di-O-sulfation, and R2 was 3-mono-O- or 3,4-di-O-sulfation, respectively. The diversity of sulfation patterns in branches complicated the structure. These results give us a new understanding of FCS Lg and provided a reliable method to decipher the FCS with complex branches. Bioanalysis of chemically modified derivatives showed that modulating the molecular mass could enhance the Xase target selectivity. Side chains conferred the Xase complex inhibition by binding to FIXa with a high affinity. Whether monosaccharide and disaccharide branches have differential effects needs to be further explored.
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CARBOHYDRATE POLYMERS
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2021
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IF 9.381
Guofeng Wu,Fenbo Ma,Yizhebang Xue,Ying Peng,Liqiu Hu,Xiaowo Kang,Qili Sun,Dong Fang Ouyang,Bin Tang,Lijun Lin
A chondroitin sulfate zinc (CSZn) complex was prepared by an ion-exchange method. The purified product was characterized by energy-dispersive X-ray spectroscopy, high-performance chromatography, elemental analysis , Fourier transform infrared spectroscopy , inductively coupled mass spectrometry , and nuclear magnetic resonance spectroscopy . The CSZn demonstrated antibacterial activity against Escherichia coli and Staphylococcus aureus and satisfied MTT cell viability (NIH3T3 fibroblasts) at ≤50 μg/mL. RT-PCR demonstrated significant promotion by CSZn of fibroblast growth factor beta (β-FGF), collagen III (COLIIIα1), vascular endothelial growth factor (VEGF) and reduction of cytokines IL-6, IL-1β & TNF-alpha. An in vivo rat full-thickness wound healing model demonstrated significant wound healing of CSZn relative to controls of saline treatment, zinc chloride treatment and chondroitin treatment. CSZn has demonstrated promising antibacterial and wound healing properties making it deserving of consideration for more advanced wound healing applications.
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ANALYTICAL CHEMISTRY
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2020
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IF 6.785
Ming Wei,Linjuan Huang,Yuxia Liu,Wanjun Jin,Xinbo Yao,Jinqiao Rong,Fan Bai,Xuezheng Song,Zhongfu Wang
The structure of chondroitin sulfate oligosaccharides (CSOs), especially their sulfation pattern, has been found to be closely related with many biological pathways and diseases. However, detailed functional analysis such as their interaction with glycan binding proteins (GBPs) has been lagging, presumably due to the unavailability of well-defined, diverse structures. Besides challenging chemical and enzymatic synthesis, this is also due to the challenges in their purification at the isomer level and structural analysis owing to their instability, structural complexity, and low mass spectrometry detection sensitivity. Herein, we first used recycling preparative HPLC to separate and purify shark CS tetrasaccharide component labeled by a bifunctional fluorescent linker 2-amino-N-(2-aminoethyl)benzamide (AEAB) at the isomer level. Then, each isomer was derivatized through a multistage procedure including N-acetylation, carboxyl amidation, permethylation, and desulfation with silylating reagent. Structural analysis of each derivatized isomer was performed with ESI-MSn in positive ion mode. A total of 16 isomers of CSO-AEAB were isolated, with a minimum mass component of 0.007 mg and a maximum mass component of 17.53 mg, of which 10 isomers (>90 μg) were structurally analyzed. This preparation and structure analysis of CSOs lay the foundation for further study of the structure–activity relationship of CSOs.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2019
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IF 3.571
Zhenjun Zhu,Xiuping Dong,Chunhong Yan,Chunqing Ai,Dayong Zhou,Jingfeng Yang,Hui Zhang,Xiaoling Liu,Shuang Song,Hang Xiao,Beiwei Zhu
Fucosylated chondroitin sulfate from sea cucumber Stichopus japonicus (FCSSJ) has been demonstrated with various biological activities; however, its precise structure is still controversial, and digestive behavior remains poorly understood. FCSSJ was purified, and its detailed structure was elucidated mainly based on the NMR spectroscopic methods. Its main chain was characterized as →4)-β-d-GlcA-(1 → 3)-β-d-GalNAc-(1→ with GalNAc4S6S:GalNAc4S in a ratio of 1.5:1, and three types of sulfated fucosyl branches attaching C-3 of GlcA, namely, Fucp2S4S, Fucp3S4S, and Fucp4S, were found in a ratio of 2:1.5:1. The digestibility of FCSSJ was investigated in vitro, and the unchanged molecular weight and reducing sugar content indicated that FCSSJ was not broken down under salivary and gastrointestinal digestion. Furthermore, FCSSJ showed a significant inhibitory impact on pancreatic lipase dose-dependently but not on α-amylase, indicating that the inhibition of pancreatic lipase by FCSSJ might be a pathway for its hypolipidemic effect. These findings propose a fucosylated chondroitin sulfate and provide insight into the mechanism of its physiological effects in the digestion system.
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International Journal of Polymeric Materials and Polymeric Biomaterials
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2019
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IF 2.263
Yajing Pan,Chao Xiao,Huaping Tan,Guoliang Yuan,Jianliang Li,Shengke Li,Yang Jia,Dangsheng Xiong,Xiaohong Hu,Xiaohong Niu
Microspheres and injectable hydrogels derived from natural biopolymers have been extensively investigated as drug carriers and cell scaffolds. In this study, we report a preparation of composite scaffolds basing microspheres and hydrogel via the Schiff’s base reaction. Hybrid gelatin/heparin microspheres loading insulin-like growth factor-1 (IGF-1) with a diameter of 5–10 µm were fabricated using an emulsion cross-linking method. Synchronously, water-soluble carboxymethyl chitosan (CMC) and oxidized chondroitin sulfate (OCS) were prepared for cross-linking of hydrogels, which were embedded with microspheres to produce a composite microspheres/gel scaffold. The mechanism of scaffold cross-linking is attributed to the Schiff’s base reaction between amino and aldehyde groups of biopolymers. Currently, gelation rate, morphology, mechanical properties, swelling ratio, weight loss, and IGF-1 release of the composite scaffolds were examined in vitro. The results show that mechanical and bioactive properties of CMC-OCS hydrogel can be significantly improved by embedding gelatin/heparin microspheres containing IGF-1. Compressive modulus of composite gel scaffolds containing 3 wt% of microspheres was 16 kPa, which was higher than the control hydrogel without microspheres. Cumulative release of IGF-1 during 7 days from microspheres embedded hydrogel was 70%, which was significantly lower than those of microspheres and hydrogels. Moreover, the composite microspheres/gel scaffolds exhibited higher swelling ratio and slower degradation rate than the control. Potential of the composite scaffolds was demonstrated by encapsulation of human adipose-derived stem cells (ASCs) in vitro. Cell culture showed that this composite hydrogel could support survival and proliferation of ASCs. These results demonstrate the potential of gelatin/heparin microspheres embedded CMC-OCS hydrogels as an injectable scaffold in soft tissue engineering.
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Polymers
·
2024
·Vol. 16
·期 20
·2876
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IF 4.7
Ling Wang,Xiaoyue Ding,Xiaorui He,Ning Tian,Peng Ding,Wei Guo,Oseweuba Valentine Okoro,Yanfang Sun,Guohua Jiang,Zhenzhong Liu,Armin Shavandi,Lei Nie
Multifunctional hydrogel dressings remain highly sought after for the promotion of skin wound regeneration. In the present study, multifunctional CHS-DA/HACC (CH) hydrogels with an interpenetrated network were constructed using hydroxypropyl trimethyl ammonium chloride modified chitosan (HACC) and dopamine-modified chondroitin sulfate (CHS-DA), using genipin as crosslinker. The synthesis of HACC and CHS-DA was effectively confirmed using Fourier transform infrared (FT-IR) analysis and1H nuclear magnetic resonance (1H NMR) spectroscopy. The prepared CH hydrogels exhibited a network of interconnected pores within the microstructure. Furthermore, rheological testing demonstrated that CH hydrogels exhibited strong mechanical properties, stability, and injectability. Further characterization investigations showed that the CH hydrogels showed favorable self-healing and self-adhesion properties. It was also shown that increasing HACC concentration ratio was positively correlated with the antibacterial activity of CH hydrogels, as evidenced by their resistance toEscherichia coliandStaphylococcus aureus. Additionally, Cell Counting Kit-8 (CCK-8) tests, fluorescent images, and a cell scratch assay demonstrated that CH hydrogels had good biocompatibility and cell migration ability. The multifunctional interpenetrated network hydrogels were shown to have good antibacterial properties, antioxidant properties, stable storage modulus and loss modulus, injectable properties, self-healing properties, and biocompatibility, highlighting their potential as wound dressings in wound healing applications.
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