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CARBOHYDRATE POLYMERS · 2024 · IF 10.7

Facilitating safe and sustained submucosal lift through an endoscopically injectable shear-thinning carboxymethyl starch sodium hydrogel

Penghui Wang,Ruixue Li,Juping Ma,Wenjie Zhang,Haifeng Shen,Yanhan Ren,Xun Zhang,Shuang Li,Bo Chi

Traditional submucosal filling materials frequently show insufficient lifting height and duration during clinical procedures. Here, the anionic polysaccharide polymer sodium carboxymethyl starch and cationic Laponite to prepare a hydrogel with excellent shear-thinning ability through physical cross-linking, so that it can achieve continuous improvement of the mucosal cushion through endoscopic injection. The results showed that the hydrogel (56.54 kPa) had a lower injection pressure compared to MucoUp (68.56 kPa). The height of submucosal lifting height produced by hydrogel was higher than MucoUp, and the height maintenance ability after 2 h was 3.20 times that of MucoUp. At the same time, the hydrogel also showed satisfactory degradability and biosafety, completely degrading within 200 h. The hemolysis rate is as low as 0.76 %, and the cell survival rate > 80 %. Subcutaneous implantation experiments confirmed that the hydrogel showed no obvious systemic toxicity. Animal experiments clearly demonstrated the in vivo feasibility of using hydrogels for submucosal uplift. Furthermore, successful endoscopic submucosal dissection was executed on a live pig stomach, affirming the capacity of hydrogel to safely and effectively facilitate submucosal dissection and mitigate adverse events, such as bleeding. These results indicate that shear-thinning hydrogels have a wide range applications as submucosal injection materials.

CAS / MDL: 9063-38-1 860-22-0
研究领域: 生物医学工程 · 材料科学 · 胃肠病学 · 生物相容性
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Injectable chitosan-polyvinylpyrrolidone composite thermosensitive hydrogels with sustained submucosal lifting for endoscopic submucosal dissection

Yang Liu,Chuang Lang,Kai Zhang,Linlin Feng,Junying Li,Tingting Wang,Siyu Sun,Guangwei Sun

To develop a submucosal injection material with sustained submucosal lifting for endoscopic submucosal dissection (ESD), this study designed and prepared a novel composite thermosensitive hydrogel system with high pH chitosan-polyvinylpyrrolidone-β-glycerophosphate (HpHCS-PVP-GP). HpHCS improved the injectability of the hydrogels and retained the rapid gelation ability at low concentrations. The modification of PVP significantly improved the stability of low-temperature hydrogel precursor solutions and the integrity of hydrogels formed at 37 °C through hydrogen bonds between PVP and HpHCS. A mathematical model was established using response surface methodology (RSM) to e v aluate the synergistic effect of HpHCS, GP , and PVP concentrations on gelation time. This RSM model and submucosal lifting evaluation using in vitro pig esophageal models were used to determine the optimal formula of HpHCS-PVP-GP hydrogels. Although the higher PVP concentration (5 % ( w / v )) prolonged gelation time, it improved hydrogel mechanical strength , resulting in better submucosal lifting performance. The experiments of Bama mini pigs showed that the heights of the cushions elevated by the HpHCS-5%PVP-GP hydrogel remained about 80 % 1 h after injection. Repeated injections were avoided, and the hydrogel had no cytotoxicity after electric cutting. Therefore, the HpHCS-PVP-GP thermosensitive hydrogel might be a promising submucosal injection material for ESD.

研究领域: 生物材料学 · 医学工程 · 消化病学
✓ 已验证 DOI PubMed 高影响因子
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Regenerative Biomaterials · 2021 ·Vol. 8 ·期 1 · IF 6.353

Accelerating ESD-induced gastric ulcer healing using a pH-responsive polyurethane/small intestinal submucosa hydrogel delivered by endoscopic catheter

Zhao Long-Mei,Gong Mei,Wang Rui,Yuan Qi-Juan,Zhang Yi,Pi Jin-Kui,Lv Xiu-He,Xie Yan,Xie Hui-Qi

Endoscopic submucosal dissection (ESD) is the standard treatment for early-stage gastric cancer, but the large post-operative ulcers caused by ESD often lead to serious side effects. Post-ESD mucosal repair materials provide a new option for the treatment of post-ESD ulcers. In this study, we developed a polyurethane/small intestinal submucosa (PU/SIS) hydrogel and investigated its efficacy for accelerating ESD-induced ulcer healing in a canine model. PU/SIS hydrogel possessed great biocompatibility and distinctive pH-sensitive swelling properties and protected GES-1 cells from acid attack through forming a dense film in acidic conditions in vitro. Besides, PU/SIS gels present a strong bio-adhesion to gastric tissues under acidic conditions, thus ensuring the retention time of PU/SIS gels in vivo. In a canine model, PU/SIS hydrogel was easily delivered via endoscopy and adhered to the ulcer sites. PU/SIS hydrogel accelerated gastric ulcer healing at an early stage with more epithelium regeneration and slight inflammation. Our findings reveal PU/SIS hydrogel is a promising and attractive candidate for ESD-induced ulcer repair.

研究领域: 生物医学工程 · 消化病学 · 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 · 2021 · IF 6.953

Chitosan thermosensitive hydrogels based on lyophilizate powders demonstrate significant potential for clinical use in endoscopic submucosal dissection procedures

Panxianzhi Ni,Sheng Ye,Renpeng Li,Jing Shan,Tun Yuan,Jie Liang,Yujiang Fan,Xingdong Zhang

The goal of this study was to develop intraoperative biomaterials for use in endoscopic submucosal dissection (ESD) procedures that are stable during storage, easy to use, and effective in clinical practice. Therefore, injectable thermosensitive hydrogels were developed based on lactobionic acid-modified chitosan/chitosan/β-glycerophosphate (CSLA/CS/GP) hydrogel lyophilizate powders, and their properties were compared with original hydrogels that had not been freeze-dried. The results indicated that the lyophilizate powders retained their thermosensitive properties, and gels could be formed within 5 min at 37 °C. Compared to the original hydrogels, the injectability of the hydrogels derived from lyophilizate powders increased significantly. These novel materials maintained their original porous network lamellar structure but exhibited improved mechanical strength and tissue adhesion. Their application with L929 and GES-1 cells revealed that the lyophilizate powder hydrogels demonstrated good cytocompatibility and clearly protected the cells in an acidic environment. The results of submucosal injection experiments involving porcine stomach tissue indicated that the heights of the cushions created by CSLA/CS/GP lyophilizate powder hydrogels lasted longer than those generated with normal saline. The thermosensitive hydrogels based on lyophilizate powders may contribute to practical clinical applications involving ESD, and may also have potential value for other applications in the digestive tract.

研究领域: 生物材料学 · 医学工程 · 消化内科
✓ 已验证 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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ADVANCED MATERIALS · 2024 ·Vol. 36 ·期 40 ·2405290 · IF 27.4

Blue Laser Triggered Hemostatic Peptide Hydrogel for Gastrointestinal Bleeding Treatment

Qiang Luo,Jie Luo,Zhaohui Luan,Kaige Xu,Lixing Tian,Kebin Zhang,Xue Peng,Mengxue Yuan,Chuanhao Zheng,Zhenzhen Shu,Yuchen Zhang,Shali Tan,Ruijue Dan,Kibret Mequanint,Chaoqiang Fan,Malcolm Xing,Shiming Yang

In an emergency, nonvariceal upper gastrointestinal bleeding (NVUGIB), endoscopic hemostasis is considered the gold standard intervention. However, current endoscopic hemostasis is very challenging to manage bleeding in large-diameter or deep lesions highly prone to rebleeding risk. Herein, a novel hemostatic peptide hydrogel (HPH) is reported, consisting of a self-assembly peptide sequence CFLIVIGSIIVPGDGVPGDG (PFV) and gelatin methacryloyl (GelMA), which can be triggered by blue laser endoscopy (BLE) for nonvariceal upper gastrointestinal bleeding treatment without recurring bleeding concerns. Upon contact with GelMA solution, PFV immediately fibrillates into β-sheet nanofiber and solvent-induced self-assembly to form HPH gel. HPH nanofiber networks induced ultrafast coagulation by enveloping blood cells and activating platelets and coagulation factors even to the blood with coagulopathy. Besides its remarkable hemostatic performance in artery and liver injury models, HPH achieves instant bleeding management in porcine NVUGIB models within 60 s by preventing the rebleeding risk. This work demonstrates an extraordinary hemostatic agent for NVUGIB intervention by BLE for the first time, broadening potential application scenarios, including patients with coagulopathy and promising clinical prospects.

CAS / MDL:
研究领域: 生物医学工程 · 材料科学 · 消化内科
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CARBOHYDRATE POLYMERS · 2021 · IF 9.381

Lactobionic acid-modified chitosan thermosensitive hydrogels that lift lesions and promote repair in endoscopic submucosal dissection

Panxianzhi Ni,Renpeng Li,Sheng Ye,Jing Shan,Tun Yuan,Jie Liang,Yujiang Fan,Xingdong Zhang

To develop a biomaterial to lift the lesion and promote wound healing in endoscopic submucosal dissection (ESD), we used lactobionic acid (LA) to improve the water solubility of chitosan (CS) and prepared a new three-phase hydrogel system with lactobionic acid-modified chitosan/chitosan/β-glycerophosphate (CSLA/CS/GP). The results indicated that the hydrogel retains temperature-sensitive properties, and CSLA obviously improved the low-temperature fluidity of the hydrogel precursor solution, enabling injection of the hydrogel by endoscopic needle. The mechanical strength and bio-adhesion of the hydrogels were also improved by the addition of CSLA and the hydrogels could be maintained in acidic environment for a few days and exhibit greater protection of cells. The CSLA/CS/GP hydrogels show good cytocompatibility. The heights of cushions elevated by CSLA/CS/GP hydrogels remained ∼ 60 % 2 h post-injection in porcine stomach models. Given the unique characteristics of these materials, the CSLA/CS/GP thermo-sensitive hydrogel is a promising intraoperative biomaterial in ESD.

研究领域: 生物材料学 · 医学工程 · 消化病学
✓ 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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CHINESE JOURNAL OF POLYMER SCIENCE · 2024 · IF 4.1

Shear-thinning Catechol-modified Chitosan Hydrogel Loaded with Silver Nanoparticles for Endoscopic Submucosal Dissection

Feng Wen-Jun,Wu Yan-He,Liu Xiao-Yang,Wang Zheng-Ke

Shear-thinning hydrogels have emerged for endoscopic submucosal dissection, while wound intervention after surgery has rarely been mentioned. Herein, a catechol-modified chitosan hydrogel with shear-thinning property was developed for simultaneously facilitating endoscopic submucosal dissection and postoperative wound healing. Benefiting from the shear-thinning and self-healing characteristics, the asprepared hydrogel showed easily endoscopic injectability. It also performed very well as submucosal cushion, which could remain above 70% after injection for 120 min in ex vivo porcine large intestine model. In fact, the cushion height of normal saline dramatically decreased to 46% of the initial height at 30 min. Ag nanoparticles encapsulated into the network endowed the hydrogel with almost reached 100% antibacterial effect against E. coli and S. aureus . The hemolysis ratio of the hydrogel was calculated to be as low as 0.8%. Combined with good hemocompatibility and cytocompatibility, the as-prepared hydrogel displayed much higher in vivo wound closure and healing efficacy than normal saline. These results demonstrated the superiority of the shear-thinning chitosan hydrogel in facilitating clinical endoscopic submucosal dissection surgery.

研究领域: 生物材料学 · 医学工程 · 药剂学
✓ 已验证 DOI 高影响因子
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SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES · 2025 · IF 2.7

Innovative staining for endoscopic screening of early esophageal cancer and precancerous lesions: a preclinical study

Gao Yuan,Li Jiachang,Xu Xiaopeng,Yu Bin,Xiang Shishuai,He Long,Zhang Yuhang,Xie Jia,Du Jiang,Hu Bing

Background Lugol’s iodine staining (LIS) solution is used to assist in esophageal chromoendoscopy. Mucosal irritation often results in uncomfortable symptoms and the risk of allergy. In the present study, we developed an extremely low-irritation, easy-to-use mucosal staining solution using polyvinyl pyrrolidone-iodine (PVP-I). This study aimed to evaluate its mucosal staining capacity and biocompatibility. Methods The mucosal staining capacity was evaluated using postoperative esophageal endoscopic submucosal dissection (ESD) specimens. After elution with vitamin C solution, the specimens were sprayed with LIS as a self-control. The effects on the “lesion area” outlined between the innovative staining and LIS were examined by the intraclass correlation coefficient (ICC) and rank-sum test. To evaluate the biocompatibility, esophageal perfusion was performed with the mice, and the esophagus and stomach were anatomized at different time points for pathological analysis. Results A total of 53 esophageal ESD specimens were stained at the endoscopy center of West China Hospital. Compared with the same concentration of LIS, the PVP-I solutions showed similar staining effects in terms of the lesion area outlined [ICC = 0.998 (> 0.75), P  = 0.733 (> 0.05)]. In live mouse experiments with esophageal perfusion, PVP-I was safer and less irritable to the esophageal gastric mucosa than LIS was, with a lower mucosal damage index (UI) and fewer inflammatory cells in pathological analysis at various time points. Conclusions The innovative PVP-I staining demonstrated effectiveness, safety, and feasibility as a mucosal staining solution for screening esophageal lesions. Further clinical studies will be carried out in the future. Graphical abstract

CAS / MDL: 7447-40-7 7553-56-2
研究领域: 肿瘤学 · 消化病学 · 内镜学 · 病理学 · 转化医学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Science Robotics · 2021 ·Vol. 6 ·期 52 · IF 23.956

Endoscopy-assisted magnetic navigation of biohybrid soft microrobots with rapid endoluminal delivery and imaging

Ben Wang,Kai Fung Chan,Ke Yuan,Qianqian Wang,Xianfeng Xia,Lidong Yang,Ho Ko,Yi-Xiang J. Wang,Joseph Jao Yiu Sung,Philip Wai Yan Chiu,Li Zhang

High-precision delivery of microrobots at the whole-body scale is of considerable importance for efforts toward targeted therapeutic intervention. However, vision-based control of microrobots, to deep and narrow spaces inside the body, remains a challenge. Here, we report a soft and resilient magnetic cell microrobot with high biocompatibility that can interface with the human body and adapt to the complex surroundings while navigating inside the body. We achieve time-efficient delivery of soft microrobots using an integrated platform called endoscopy-assisted magnetic actuation with dual imaging system (EMADIS). EMADIS enables rapid deployment across multiple organ/tissue barriers at the whole-body scale and high-precision delivery of soft and biohybrid microrobots in real time to tiny regions with depth up to meter scale through natural orifice, which are commonly inaccessible and even invisible by conventional endoscope and medical robots. The precise delivery of magnetic stem cell spheroid microrobots (MSCSMs) by the EMADIS transesophageal into the bile duct with a total distance of about 100 centimeters can be completed within 8 minutes. The integration strategy offers a full clinical imaging technique–based therapeutic/intervention system, which broadens the accessibility of hitherto hard-to-access regions, by means of soft microrobots.

研究领域: 生物医学工程 · 机器人学 · 纳米技术 · 医学成像 · 靶向药物递送 · 生物工程
✓ 已验证 DOI 高影响因子
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Journal of Biomedical Nanotechnology · 2022 ·Vol. 18 ·期 2 ·607-615 · IF 3.641

Analysis of the Relationship Between Periampullary Diverticulum and Recurrent Bile Duct Stones After Endoscopy on Magnetic Resonance Imaging of Magnetic Nanoparticles

Wang Yingkai,Jie Jiepeng,Qian Bo,Qiao Yongping,Yu Pengming,Zhang Jijun

The objective of this work was to investigate the effect of magnetic resonance cholangiopancreatography (MRCP) based on super-paramagnetic iron oxide nanoparticles (SPIONs) on the recurrence diagnosis of periampullary diverticulum (PAD) and bile duct stone (BDS), so as to provide a scientific research basis for the recidivation factors of bile duct stones in clinic. Patients with PAD diagnosed in hospital from July 2019 to March 2021 (who had undergone endoscopic gallstone surgery) were selected for study in this work. They were rolled into two groups, the parapapillary group (123 cases) and the cholangiopancreatic duct directly opening in the diverticulum group (97 cases), according to the clinical classification. Then, 100 patients without PAD who had undergone bile duct node therapy were selected as the control group. The recidivation of BDS, serological index, and biliary pressure index before and after treatment were compared. The relationship between PAD and recidivation of bile duct stones was analyzed. The results showed that the average particle size, hydration kinetic particle size, effective time, and duration of polyethylene glycol (PEG)/polyethyleneimine (PEI)/poly aspartic acid-super-paramagnetic iron oxide nanoparticles(PASP-SPIONs) were better than PEG/PEI-SPIONs and SPIONs. The recidivation rate of BDS in Groups R and X was remarkably higher than the rate in control group (P < 0.05). Before treatment, common bile duct pressure in the control group was lower obviously than that in Groups R and X (P < 0.05). After treatment, the indexes including total bilirubin, direct bilirubin, and alkaline phosphatase in control group were lower than those in Groups R and X (P < 0.05). The incidence of complications in Groups R and X was much higher than in contrast to the control group (P < 0.05). Therefore, PEG/PEI/PASP-SPIONs had good contrast effect and could be used as magnetic resonance imaging contrast agent. Complications such as common bile duct pressure and infection were increased by PAD, which may be the main factor for the recidivation of BDS.

研究领域: 医学影像 · 胃肠病学 · 纳米技术 · 临床研究
✓ 已验证 DOI PubMed 高影响因子
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