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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2022 · IF 8.025

Injectable shear-thinning sodium alginate hydrogels with sustained submucosal lift for endoscopic submucosal dissection

Juping Ma,Penghui Wang,Chuanfei Tang,Huiyun Liao,Wenjie Zhang,Rong Yang,Tianqi Shi,Xiaoyan Tan,Bo Chi

Endoscopic submucosal dissection (ESD) is one of the most effective approaches for the minimally invasive treatment of early gastrointestinal cancers. Submucosal injections help safely and successfully remove lesions during ESD by elevating the mucosa and separating the submucosal muscle layer. Herein, we report dynamic injectable sodium alginate hydrogels (ISAHs) with shear-thinning for ESD surgery, which were easily fabricated by the sulfhydryl group of GSH-modified sodium alginate (SA-GSH) reacting with the aldehyde group of oxidized sodium alginate (OSA) at room temperature. ISAHs have advantageous self-healing abilities and antioxidant activity. Additionally, according to an in vitro test on porcine colorectal submucosal lifting, the submucosal elevation heights created by ISAHs were 13 % -18 % greater than those created by commercial ESD solutions (0.4  w / v % sodium hyaluronate). These properties and biocompatibility were confirmed in vitro and in vivo experiments. ISAHs will hopefully become a novel submucosal injectable hydrogel to assist ESD surgery.

研究领域: 胃肠病学 · 生物医学工程 · 材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

Hyaluronic acid-based composite hydrogels embedded with core-shell microgels with properties of mucosal adhesion and combined drug administration for chemoradiotherapy induced oral mucositis

Yingying Wu,Lei Jiang,Kesang Li,Jialin Liu,Ping Chen,Jianfen Xu,Jiantao Zhang

Chemoradiotherapy-induced oral mucositis (CIOM), characterized by high incidence and delayed healing, severely impairs patient recovery and quality of life. Current treatments face challenges due to poor wet adhesion, dynamic oral environments, and lack of multiple active substances for mucosal repair. This situation makes an urgent need for therapeutic platforms that combine robust mucosal adhesion with multifunctionality. In this study, a crosslinked hyaluronic acid based hydrogel (PHB) embedded with core-shell microgels was developed. Core-shell microgels were fabricated to encapsulate growth factor (core) and lidocaine (shell), enabling spatiotemporal drug release. The hydrogel exhibited superior mucosal adhesion, with a displacement of only 5.5 mm after 24 h on an inclined agar plate containing mucin, attributed to hydrogen bonding between hydroxyl groups of PHB and mucin. The bacteriostasis experiment results show that PHB has excellent antibacterial properties against E. coli and S. aureus , which can help to prevent the growth of oral bacteria and promote wound healing. Furthermore, sustained release of EGF and lidocaine from the PHB hydrogel was maintained for 24 h, aligning with the time window required for oral mucosal repair.. In vivo studies demonstrated PHB hydrogels accelerated mucosal proliferation and remodeling in CIOM in golden hamsters. This study presents a combined drug hydrogel system addressing CIOM's multifactorial pathology. The PHB platform synergizes prolonged wet adhesion, antibacterial action, analgesia, and tissue regeneration, offering a clinically solution for oral mucosal repair.

研究领域: 生物医学工程 · 口腔医学 · 药剂学 · 组织工程 · 黏膜修复学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Applied Materials & Interfaces · 2021 · IF 9.229

Injectable Thermogel Generated by the “Block Blend” Strategy as a Biomaterial for Endoscopic Submucosal Dissection

Shuquan Cui,Yiman Wei,Qiao Bian,Yan Zhu,Xiaobin Chen,Yaping Zhuang,Mingyan Cai,Jingyu Tang,Lin Yu,Jiandong Ding

Endoscopic submucosal dissection is an established method for the removal of early cancers and large lesions from the gastrointestinal tract but is faced with the risk of perforation. To decrease this risk, a submucosal fluid cushion (SFC) is needed clinically by submucosal injection of saline and so on to lift and separate the lesion from the muscular layer. Some materials have been tried as the SFC so far with disadvantages. Here, we proposed a thermogel generated by the “block blend” strategy as an SFC. This system was composed of two amphiphilic block copolymers in water, so it was called a “block blend”. We synthesized two non-thermogellable copolymers poly(d,l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) and blended them in water to achieve a sol–gel transition upon heating in both pure water and physiological saline. We explored the internal structure of the resultant thermogel with transmission electron microscopy, three-dimensional light scattering, 13C NMR, fluorescence resonance energy transfer, and rheological measurements, which indicated a percolated micelle network. The biosafety of the synthesized copolymer was preliminarily confirmed in vitro. The main necessary functions as an SFC, namely, injectability of a sol and the maintained mucosal elevation as a gel after injection, were verified ex vivo. This study has revealed the internal structure of the block blend thermogel and illustrated its potential application as a biomaterial. This work might be stimulating for investigations and applications of intelligent materials with both injectability and thermogellability of tunable phase-transition temperatures.

CAS / MDL: 120-12-7 85-01-8
研究领域: 生物医学工程 · 材料科学 · 消化病学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOMATERIALS · 2021 · IF 12.479

Shell-mediated phagocytosis to reshape viral-vectored vaccine-induced immunity

Fengling Feng,Haibin Hao,Jin Zhao,Yanjun Li,Ying Zhang,Ruiting Li,Ziyu Wen,Chunxiu Wu,Minchao Li,Pingchao Li,Ling Chen,Ruikang Tang,Xiaoyu Wang,Caijun Sun

Adenovirus (Ad) has been extensively developed as a gene delivery vector, but the potential side effect caused by systematic immunization remains one major obstacle for its clinical application. Needle-free mucosal immunization with Ad-based vaccine shows advantages but still faces poor mucosal responses. We herein report that the chemical engineering of single live viral-based vaccine effectively modulated the location and pattern of the subsequently elicited immunity. Through precisely assembly of functional materials onto single live Ad particle, the modified virus entered host cell in a phagocytosis-dependent manner, which is completely distinct from the receptor-mediated entry of native Ad. RNA-Seq data further demonstrated that the modified Ad-induced innate immunity was sharply reshaped via phagocytosis-related pathway, therefore promoting the activation and mature of antigen presentation cells (APC). Moreover, the functional shell enabled the modified Ad-based vector with enhanced muco-adhesion to nasal tissues in mice, and then prolonged resident time onto mucosal surface, leading to the robust mucosal IgA production and T cell immunity at local and even remote mucosal-associated lymphoid tissues. This study demonstrated that vaccine-induced immunity can be well modulated by chemistry engineering, and this method provides the rational design for needle-free mucosa-targeting vaccine against a variety of emerging infectious diseases.

研究领域: 病毒学 · 免疫学 · 生物医学工程 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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Frontiers in Bioengineering and Biotechnology · 2023 · IF 5.7

Drug-loaded mucoadhesive microneedle patch for the treatment of oral submucous fibrosis

Xian Cheng,Yanqing Yang,Zhengwei Liao,Qiao Yi,Yueying Zhou,Xiaohan Dai,Yanping Liu,Ousheng Liu

Oral submucous fibrosis is a chronic, inflammatory and potentially malignant oral disease. Local delivery of triamcinolone to lesion site is a commonly used therapy. The existing methods for local drug delivery include topical administration and submucosal injection. However, in the wet and dynamic oral microenvironment, these methods have drawbacks such as limited drug delivery efficiency and injection pain. Therefore, it is urgently needed to develop an alternative local drug delivery system with high efficiency and painlessness. Inspired by the structure of band-aid, this study proposed a novel double-layered mucoadhesive microneedle patch for transmucosal drug delivery. The patch consisted of a mucoadhesive silk fibroin/tannic acid top-layer and a silk fibroin microneedle under-layer. When applying the annealing condition for the medium content of β-sheets of silk fibroin, the microneedles in under-layer displayed both superior morphology and mechanical property. The mechanical strength of per needle (0.071N) was sufficient to penetrate the oral mucosa. Sequentially, the gelation efficiency of silk fibroin and tannic acid in top-layer was maximized as the weight ratio of tannic acid to silk fibroin reached 5:1. Moreover, in vitro results demonstrated the double-layered patch possessed undetectable cytotoxicity. The sustained release of triamcinolone was observed from the double-layered patch for at least 7 days. Furthermore, compared with other commercial buccal patches, the double-layered patch exhibited an enhanced wet adhesion strength of 37.74 kPa. In addition, ex vivo mucosal tissue penetration experiment confirmed that the double-layered patch could reach the lamina propria, ensuring effective drug delivery to the lesion site of oral submucous fibrosis. These results illustrate the promising potential of the drug-loaded mucoadhesive microneedle patch for the treatment of oral submucous fibrosis.

CAS / MDL: 7550-35-8 497-19-8
研究领域: 药学 · 生物医学工程 · 材料科学 · 牙科医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Microbiology · 2023 · IF 5.2

Impacts of sodium butyrate on intestinal mucosal barrier and intestinal microbial community in a weaned piglet model

Liu Han,Zhao Jing,Zhang Wenju,Nie Cunxi

Objective: Butyrate is thought to enhance intestinal mucosal homeostasis, but the detailed mechanism remains unclear. Therefore, further investigation on the mechanism of butyrate regulation of intestinal mucosal homeostasis was performed.Materials and methods: This study used weaned piglets with similar intestinal metabolic function to humans as a research model. The dietary supplemented 0.2% sodium butyrate group (0.2% S) and negative control group (CON) were established to detect the effects of butyrate on growth performance, intestinal tissue morphology, mucosal barrier function, and intestinal microbial community structure in weaned piglets.Results: There was an increase in average daily gain (ADG) during three different experimental periods and a reduction in average daily feed intake (ADFI) and feed-to-gain ratio (F:G) during days 1–35 and days 15–35 in 0.2% S compared with CON (P > 0.05). Furthermore, villus height in the ileum and duodenum was increased, and crypt depths in the colon and jejunum were reduced in both groups (P < 0.05). Moreover, the ratio of villus height and crypt depth (V/C) in 0.2% S both in the ileum and jejunum was significantly increased (P < 0.05) compared with CON. The relative mRNA expression of PKC, MUC1, CLDN1, and ITGB1 was upregulated in the ileum of 0.2% S compared with CON (P < 0.05). The digesta samples of 0.2% S, both in the ileum (P < 0.05) and colon, contained greater intestinal bacterial abundance and diversity of probiotics, including Lactobacillus, Streptococcus, Megasphaera, and Blautia, which promoted amino acid metabolism and energy production and conversion in the colon and the synthesis of carbon-containing biomolecules in the ileum.Conclusion: In summary, dietary supplementation with 0.2% sodium butyrate was shown to have a tendency to improve the growth performance of weaned piglets and enhance intestinal mucosal barrier function via altering the gut microbiota.

CAS / MDL: 156-54-7
研究领域: 动物营养学 · 微生物学 · 胃肠病学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Bioengineering and Biotechnology · 2024 · IF 4.3

Injectable temperature-sensitive hydrogel facilitating endoscopic submucosal dissection

Xu Ruifen,Yang Xiaoyu,Yi Tong,Tan Tao,Li Zhongqi,Feng Xuyang,Rao Jing,Zhou Pinghong,Hu Hao,Zhan Yonghua

Purpose: Early gastrointestinal tumors can be removed by endoscopic procedures. Endoscopic mucosal dissection (ESD) requires submucosal fluid injection to provide mucosal elevation and prevent intraoperative perforation. However, the clinically applied normal saline mucosal elevation height is low for a short time, which often requires multiple intraoperative injections that increase the inconvenience and procedure time. In addition, recently researched submucosal injection materials (SIM) suffer from complex preparation, poor economy, and poor biocompatibility. Therefore, there is an urgent need for a new type of SIM that can provide long, safe and effective mucosal elevation in support of the endoscopic procedures.Methods: The FS hydrogel is based on polyethylene-polypropylene glycol (F-127) mixed with sodium alginate (SA). The different physicochemical properties of FS hydrogels were characterized through various experiments. Afterward, various biosafety assessments were carried out. Finally, the performance of FS hydrogels was evaluated by in vitro submucosal injection and in vivo swine ESD.Results: The experimental results show that the FS hydrogel is liquid at room temperature, making it easy to inject, and when injected under the mucosa, it undergoes temperature-induced cross-linking, transforming from a liquid to a solid state to provide long-lasting mucosal augmentation. At the same time, the FS hydrogel exhibits controllable gelation, stability, and biocompatibility. The results of in vitro submucosal injections and in vivo ESD procedures showed that FS achieves high mucosal augmentation and provides good submucosal cushioning in the long term.Conclusion: In summary, the F-127/SA hydrogel is simple to synthesize, cost-effective, safe, easy to store, and able to assist ESD well from the perspective of practical clinical problems, indicating that the FS hydrogel can be an ideal potent submucosal injection substitution.

CAS / MDL: 67-68-5 9005-38-3
研究领域: 胃肠病学 · 生物医学工程 · 材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Temperature-sensitive injectable chitosan-based hydrogel for endoscopic submucosal dissection

Shourui Liu,Ruibao Ju,Zhenguo Zhang,Zhen Jiang,Jingzhao Cui,Wanshun Liu,Baoqin Han,Shuo Wang

Endoscopic submucosal dissection (ESD) is an effective treatment for polyps and early gastrointestinal cancers, but requires a high level of operator skill. Injecting submucosal materials (SIM) helps create a fluid cushion between the mucosal and muscular layers, making the procedure easier and reducing associated risks. However, SIMs commonly used in current clinical practice tend to spread quickly and fail to provide long-lasting submucosal fluid cushions (SFC). Thus, there is a critical need for a material that is easy to inject while also maintaining a durable barrier. We prepared succinylated hydroxybutyl chitosan (HBC-SA) by adding succinic anhydride (SA) to hydroxybutyl chitosan (HBC). The hydrogel had excellent temperature-sensitive properties and was able to be injected via an endoscopic injection needle even after gel formation. In vitro and in vivo studies showed that it has satisfactory biocompatibility. Functional experiments showed that the submucosal lifting properties of this hydrogel were significantly better than that of normal saline (NS) and sodium hyaluronate (SH), two commonly used clinical materials. In addition, the hydrogel possessed excellent hemostatic properties. Based on these results, HBC-SA is a promising candidate for submucosal injection during ESD.

CAS / MDL: 106-88-7
研究领域: 胃肠病学 · 生物医学工程 · 材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CELL BIOCHEMISTRY AND BIOPHYSICS · 2024 · IF 1.8

Curcumin Alleviates Arecoline-induced Oral Submucous Fibrosis via the FOSL1/MAPK8 Axis

Yin Lifen,Wang Xiao

Oral submucous fibrosis (OSF) is a precancerous lesion of the oral cavity. Areca nut consumption can cause OSF through sustained activation of buccal mucosal fibroblasts (BMFs). This study explored the effect of curcumin on arecoline-induced BMF activation and its mechanism of action. BMFs were isolated and identified by immunofluorescence detection of fibroblast surface markers vimentin and S100A4. After transfection with FOSL1- or MAPK8-related vectors, BMFs were activated by arecoline and treated with curcumin. Scratch and transwell assays were performed to detect cell migration. ChIP and luciferase reporter assays were conducted to detect the binding of FOSL1 to the MAPK8 promoter. RT-qPCR was used to detect FOSL1 and MAPK8 mRNA expression. Western blotting was used to detect FOSL1, MAPK8, COL1A1, α-SMA, Smad2, and p-Smad2 proteins. Curcumin treatment inhibited arecoline-induced fibroblast migration, reduced the expression of myofibroblast markers COL1A1, α-SMA, and p-Smad2, and downregulated the expression of FOSL1 and MAPK8. FOSL1 or MAPK8 overexpression enhanced migration and increased COL1A1, α-SMA, and p-Smad2 expression in curcumin-treated cells. FOSL1 bound to the MAPK8 promoter and promoted MAPK8 expression. Simultaneous FOSL1 overexpression and MAPK8 knockdown, compared to FOSL1 overexpression, reduced cell migration and inhibited COL1A1, α-SMA, and p-Smad2 expression. In conclusion, curcumin targets FOSL1 to reduce MAPK8 expression, thereby suppressing arecoline-induced fibroblast activation.

CAS / MDL: 63-75-2
研究领域: 药理学 · 分子生物学 · 肿瘤学 · 牙医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Physiology · 2023 · IF 4

Ammonia nitrogen stress damages the intestinal mucosal barrier of yellow catfish (Pelteobagrus fulvidraco) and induces intestinal inflammation

Senyue Liu,Lin Luo,Fengyuan Zuo,Xiaoli Huang,Liang Zhong,Sha Liu,Yi Geng,Yangping Ou,Defang Chen,Wenlong Cai,Yongqiang Deng

Nitrogen from ammonia is one of the most common pollutants toxics to aquatic species in aquatic environment. The intestinal mucosa is one of the key mucosal defenses of aquatic species, and the accumulation of ammonia nitrogen in water environment will cause irreversible damage to intestinal function. In this study, histology, immunohistochemistry, ultrastructural pathology, enzyme activity analysis and qRT-PCR were performed to reveal the toxic effect of ammonia nitrogen stress on the intestine of Pelteobagrus fulvidraco . According to histological findings, ammonia nitrogen stress caused structural damage to the intestine and reduced the number of mucous cells. Enzyme activity analysis revealed that the activity of bactericidal substances (Lysozyme, alkaline phosphatase, and ACP) had decreased. The ultrastructure revealed sparse and shortened microvilli as well as badly degraded tight junctions. Immunohistochemistry for ZO-1 demonstrated an impaired intestinal mucosal barrier. Furthermore, qRT-PCR revealed that tight junction related genes ( ZO-1, Occludin, Claudin-1 ) were downregulated, while the pore-forming protein Claudin-2 was upregulated. Furthermore, as ammonia nitrogen concentration grew, so did the positive signal of Zap-70 (T/NK cell) and the expression of inflammation-related genes ( TNF , IL-1β , IL-8, IL-10) . In light of the above findings, we conclude that ammonia nitrogen stress damages intestinal mucosal barrier of Pelteobagrus fulvidraco and induces intestinal inflammation.

CAS / MDL: 886-86-2
研究领域: 水生毒理学 · 环境科学 · 鱼类生理学 · 免疫学 · 分子生物学
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JOURNAL OF CONTROLLED RELEASE · 2025 · IF 11.5

Gastric-mucus penetrating and responsive microgels for alleviating Helicobacter pylori-induced gastritis

Xing Li,Jipeng Zhang,Xiangyu Liu,Zijian Wu,Zhipeng Yu,Wen Zhang,Yuanzhi Wang,Zekun Li,Martien A. Cohen Stuart,Leonard M.C. Sagis,Minchun Lv,Jie Xiao,Yuan Li

Helicobacter pylori ( H. pylori ) is a prevalent global pathogen responsible for gastritis and the potential development of gastric cancer. Sulforaphane (SFN), a foodborne compound, exhibits notable antibiotic properties against H. pylori . However, its utility is limited by poor stability and susceptibility to environmental degradation. Here, we developed a gastric-responsive-release microgel for delivering anti- H. pylori SFN. The microgels were prepared by cross-linking α-lactalbumin nanotubes then coated with chitosan (CTS-MGs). SFN was loaded into microgels with a loading rate of 10.73 ± 0.25 %. The CTS-MG showed a strong adhesion to the gastric mucosa, prolonging gastric retention for up to 24 h and responsively releasing SFN in the stomach. Furthermore, CTS-MG/SFN dissociated and released nanotubes/SFN, which could penetrate into the gastric mucus layer and arrive at the deepest mucus sites where most H. pylori were colonized. Our results revealed that CTS-MG/SFN displayed an obvious inhibitory effect against H. pylori . The oral administration of CTS-MG/SFN in H. pylori -infected mice effectively alleviated H. pylori -induced gastritis and modulated gastric microbiota homeostasis. This work demonstrated high potential of CTS-MG microgels for gastric-targeted and oral delivery of antibiotic natural compounds against H. pylori infection.

CAS / MDL: 4478-93-7 9005-65-6
研究领域: 药学 · 微生物学 · 生物材料学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Pharmaceutics · 2024 ·Vol. 16 ·期 1 ·154 · IF 4.9

Chitosan-Functionalized Poly(β-Amino Ester) Hybrid System for Gene Delivery in Vaginal Mucosal Epithelial Cells

Xueqin Gao,Dirong Dong,Chong Zhang,Yuxing Deng,Jiahui Ding,Shiqi Niu,Songwei Tan,Lili Sun

Gene therapy displays great promise in the treatment of cervical cancer. The occurrence of cervical cancer is highly related to persistent human papilloma virus (HPV) infection. The HPV oncogene can be cleaved via gene editing technology to eliminate carcinogenic elements. However, the successful application of the gene therapy method depends on effective gene delivery into the vagina. To improve mucosal penetration and adhesion ability, quaternized chitosan was introduced into the poly(β-amino ester) (PBAE) gene-delivery system in the form of quaternized chitosan-g-PBAE (QCP). At a mass ratio of PBAE:QCP of 2:1, the polymers exhibited the highest green fluorescent protein (GFP) transfection efficiency in HEK293T and ME180 cells, which was 1.1 and 5.4 times higher than that of PEI 25 kD. At this mass ratio, PBAE–QCP effectively compressed the GFP into spherical polyplex nanoparticles (PQ–GFP NPs) with a diameter of 255.5 nm. In vivo results indicated that owing to the mucopenetration and adhesion capability of quaternized CS, the GFP transfection efficiency of the PBAE–QCP hybrid system was considerably higher than those of PBAE and PEI 25 kD in the vaginal epithelial cells of Sprague–Dawley rats. Furthermore, the new system demonstrated low toxicity and good safety, laying an effective foundation for its further application in gene therapy.Keywords:gene delivery;poly(β-amino ester);chitosan;mucoadhesion

研究领域: 生物医学工程 · 基因治疗
✓ 已验证 产品关联 DOI PubMed 高影响因子
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