Submucosal Injection Material Research Articles

Novel submucosal injection material comprising fully synthetic and self-assembling peptide solution in endoscopic submucosal dissection: A pilot study

Endoscopic submucosal dissection (ESD) requires an injection solution to create a submucosal cushion for safe endoscopic resection. This study evaluated the safety and feasibility of a new injection solution (PuraLift) in ESD for early-stage gastrointestinal tumors. This prospective, single-arm, single-center pilot study included eleven patients with gastrointestinal neoplasms of the stomach (n=5) or colorectum (n=6) who underwent ESD. All patients underwent outpatient follow-up at week 4 to confirm the presence or absence of adverse events. All underwent protocol treatment and post-treatment follow-up. None of the adverse events were judged to have a cause-and-effect relationship with the study. Questionnaires to the operators who performed the protocol treatment and assistants who performed submucosal injections were evaluated in comparison to saline, and maintenance of mucosal lifting was long, comparable, and short (9/2/0). En bloc and R0 resections were achieved in all patients without intraprocedural adverse events. The median size of the specimens was 40 (range, 20–70) mm. The median excision time was 52 (range, 22–130) min. The median volume of PuraLift was 32 (range, 22–130) mL. No postoperative bleeding or delayed perforation was observed in any patient. The novel injectable material, PuraLift, can potentially ensure safe and feasible in ESD.

Elevation and adhesion properties of injectable hydrogels based on catechol/boronic acid-modified Alaska pollock gelatin for endoscopic submucosal dissection

Elevation of early-stage gastrointestinal cancer using submucosal injection materials (SIMs) and postoperative wound care with adhesive materials are crucial for preventing complications arising from endoscopic submucosal dissection (ESD). Several types of SIMs have been developed; however, they often provide insufficient tissue elevation and fail to adequately adhere to the defect following the removal of early-stage gastrointestinal cancer. In this study, we present the development of injectable Cat-PBA-ApGltn hydrogels, which are based on catechol group-modified Alaska pollock gelatin (Cat-ApGltn) and phenylboronic acid-modified Alaska pollock gelatin (PBA-ApGltn), serving as multifunctional SIMs. A Cat-ApGltn/PBA-ApGltn mixed solution formed a hydrogel within 3 seconds. The resulting Cat-PBA-ApGltn hydrogels were easily injected manually through a 23 G needle due to their shear-thinning properties. Additionally, 10 w/v% Cat-PBA-ApGltn hydrogels demonstrated a 2.3-fold increase in mucosal elevation (7.2 ± 0.4 mm) compared with a commercially available SIM (3.1 ± 0.7 mm). The 10 w/v% Cat-PBA-ApGltn hydrogel, when adhered to porcine gastric submucosa, exhibited a burst strength 7 times greater than the average human intragastric pressure. Furthermore, the Cat-PBA-ApGltn hydrogels demonstrated biodegradability without inducing severe inflammation upon implantation in rat subcutaneous tissue. These Cat-PBA-ApGltn hydrogels hold promise as multifunctional SIMs, boasting injectability, excellent elevation, adhesion capabilities, and biodegradability.

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

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 evaluate 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.

Synergistic Drug-Loaded Shear-Thinning Star Polymer Hydrogel Facilitates Gastrointestinal Lesion Resection and Promotes Wound Healing.

Easy injection, long-lasting barrier, and drug loading are the critical properties of submucosal injection materials for endoscopic surgery. However, conventional injectable polymers face challenges in simultaneously attaining these properties due to the inherent conflict between injectability and in situ stability. Here, a multi-arm star polymer hydrogel (denoted as βCP hydrogel) with long-lasting submucosal barrier (exceeding 120 min), rapid hemostasis, and sustained antibacterial properties is successfully developed by grafting poly(oligo(ethylene glycol) methyl ether methacrylate)(PEGMA) side-chains from β-CD via atom transfer radical polymerization (ATRP). During the onset of shearing, βCP hydrogel experiences the unwinding of polymer side-chains between neighboring star polymers, which facilitates the process of endoscopic injectability. After submucosal injection, βCP hydrogel undergoes the winding of polymer side-chains, thereby establishing a long-lasting barrier cushion. Meanwhile, owing to its distinctive structures with a hydrophobic inner cavity and an outer layer of hydrophilic polymer side-chains, βCP hydrogel enables simultaneous loading and on-demand release of diverse categories ofdrugs. This unique performance can adapt to the diverse demands during different stages of wound healing in a porcine endoscopic surgery model. These results indicate an appealing prospect for new application of star polymers as a good submucosal injection material in endoscopic treatments.

Injectable temperature-sensitive hydrogel facilitating endoscopic submucosal dissection.

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.

Injectable Modified Sodium Alginate Microspheres for Enhanced Operative Efficiency and Safety in Endoscopic Submucosal Dissection.

Endoscopic submucosal dissection (ESD) is an effective method for resecting early-stage tumors in the digestive system. To achieve a low injection pressure of the injected fluid and continuous elevation of the mucosa following injection during the ESD technique, we introduced an innovative injectable sodium-alginate-based drug-loaded microsphere (Cipro-ThSA) for ESD surgery, which was generated through an emulsion reaction involving cysteine-modified sodium alginate (ThSA) and ciprofloxacin. Cipro-ThSA microspheres exhibited notable adhesiveness, antioxidant activity, and antimicrobial properties, providing a certain level of postoperative wound protection. In vitro cell assays confirmed the decent biocompatibility of the material. Lastly, according to animal experiments involving submucosal elevation of porcine colons, Cipro-ThSA microspheres ensure surgically removable lift height while maintaining the mucosa for approximately 246% longer than saline, which could effectively reduce surgical risks while providing sufficient time for operation. Consequently, the Cipro-ThSA microsphere holds great promise as a novel submucosal injection material, in terms of enhancing the operational safety and effectiveness of ESD surgery.

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

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.

Efficacy and safety of a submucosal injection solution of sodium alginate for endoscopic resection in a porcine model

Endoscopic resection techniques require the use of submucosal injection. Normal saline and sodium hyaluronate solutions are mainly used for this purpose, but an ideal solution has not yet been developed. The aim of this study was to assess a new solution, MC-003—a novel submucosal injection solution developed with sodium alginate as the main ingredient. Normal saline, a commercial sodium hyaluronate solution (Endo-Ease), and MC-003 were examined. A total of 18 gastric submucosal cushions were created in the stomachs of six pigs. The height of mucosal elevation was measured sequentially using endoscopic sonography. After euthanizing the animals either 2 h or 5 days after the procedure, pathologic examination was performed for each injection site. Although not statistically significant over the entire study period, MC-003 showed a superior result to normal saline and an equivalent result to Endo-Ease in the submucosal cushion height and its rate of decrease. There were no adverse outcomes after injection of the three solutions and there was no pathologically identified detrimental change in the resected specimens. MC-003 creates a sufficient submucosal fluid cushion without apparent tissue damage. It can be considered as an effective submucosal injection material.

A novel submucosal injection material comprising a fully synthetic and self-assembling peptide solution for endoscopic resection of large colorectal laterally spreading tumors.

An injection solution is required to create a submucosal cushion to allow safe endoscopic resection [1] [2]. The fully synthetic and self-assembling peptide solution submucosal injection material (PuraLift; 3-D Matrix, Tokyo, Japan) is a non-biologic preparation that self-assembles to create a gel formed of nanofibers when in contact with a neutral pH [3]. It has the same ingredients as the peptide hemostatic agent (PuraStat; 3-D Matrix) [4]. Here we report the first two cases of the use of PuraLift ([Video 1]).

Easily-injectable shear-thinning hydrogel provides long-lasting submucosal barrier for gastrointestinal endoscopic surgery

Submucosal injection material has shown protective effect against gastrointestinal injury during endoscopic surgery in clinic. However, the protective ability of existing submucosal injection material is strictly limited by their difficult injectability and short barrier time. Herein, we report a shear-thinning gellan gum hydrogel that simultaneously has easy injectability and long-lasting barrier function, together with good hemostatic property and biocompatibility. Shear-thinning property endows our gellan gum hydrogel with excellent endoscopic injection performance, and the injection pressure of our gellan gum hydrogel is much lower than that of the small molecule solution (50 wt% dextrose) when injected through the endoscopic needle. More importantly, our gellan gum hydrogel shows much stronger barrier retention ability than normal saline and sodium hyaluronate solution in the ex vivo and in vivo models. Furthermore, our epinephrine-containing gellan gum hydrogel has a satisfactory hemostatic effect in the mucosal lesion resection model of pig. These results indicate an appealing application prospect for gellan gum hydrogel utilizing as a submucosal injection material in endoscopic surgery.

Comparison of sodium alginate-based and sodium hyaluronate-based submucosal injection materials based on rheological analysis

As a viscous high-performance submucosal injection material (SIM) used in endoscopic submucosal dissection (ESD), sodium alginate-based SIM (SA-SIM) was recently introduced as high-performance SIM equivalent to sodium hyaluronate-based SIM (HA-SIM) in Japan. However, a comprehensive, detailed comparison of SA and HA is yet to be performed. In this study, we precisely measured the viscoelastic properties, submucosal elevation height (SEH), and injection pressure (IP). Furthermore, we compared the outcomes of ESD using an ex vivo ESD model. There was no significant difference in SEHs between HA-SIM and SA-SIM at all post-injection times, and the IP of the SA-SIM injection was significantly higher than that of the HA-SIM injection in all conditions (P < 0.0001). The viscosity at high shear rates of SA-SIM was higher than that of HA-SIM; this result was consistent with SEH/IP measurement results. No significant difference was observed in ESD procedure time and total volume of injected SIM between HA-SIM and SA-SIM (18.1 ± 6.7 and 17.8 ± 6.0 min, P = 0.8987; 13.3 ± 5.3 and 11.6 ± 5.9 ml, P = 0.4658, respectively). Although SA-SIM was slightly more difficult to inject than HA-SIM, there was no significant difference in performance between the materials. Thus, this basic study demonstrated that SA-SIM can be used for endoscopic treatment as well as HA-SIM, and supported previous clinical research data.

The feasibility of a fully synthetic and self-assembled peptide solution as submucosal injection material: a preliminary animal study

Background and aim An injection solution is required to create a submucosal cushion (SMC) for safe endoscopic resection procedures. The aim of this preliminary animal study was to clarify the safety and efficacy of a novel fully synthetic and self-assembled peptide (FSSP) solution as a submucosal injection material (SMIM). Method To compare the submucosal-lifting properties, 0.3% FSSP, Eleview®, sodium hyaluronate acid solution (SHA) and normal saline (NS) were randomly injected using an injection needle into the submucosa of exposed stomach and colon in five living dogs in a blind fashion. The mean height, and volume of SMCs were measured using a digital caliper immediately and 10, 20, 30, and 40 min after injecting each solution. All resected specimens were examined histopathologically. Results In both the colon and stomach, ANOVA for repeated measures showed the significant interaction between time and solution for the time-dependent change in the height. In the colon, FSSP created significantly higher SMC than NS 20 min after injection (p = .0015) and Eleview® and NS 40 min after injection (p = .0009 and p = .0002). Furthermore, FSSP and SHA tended to maintain height and volume when compared to the other two solutions. In the stomach, FSSP and SHA tended to maintain height and volume when compared to the other two solutions. There were no significant differences between the histopathological finding and the injecting solutions used. Conclusion FSSP seems to be useful as a SMIM for endoscopic resection especially in the colon. Further studies are needed prior to clinical use of FSSP.

Differences between two sodium hyaluronate-based submucosal injection materials currently used in Japan based on viscosity analysis

In Japan, two 0.4% sodium hyaluronate (HA)-based submucosal injection materials (SIMs) are currently used in endoscopic submucosal dissection (ESD): MucoUp (HA-Mc) and Ksmart (HA-Ks). HA-Mc and HA-Ks have the same concentration and are, thus, construed by most endoscopists to have no difference. Nevertheless, visual observation conveys the impression that HA-Ks have a higher viscosity than HA-Mc, suggesting that HA-Ks performs better than HA-Mc. This study aimed to examine the differences between HA-Mc and HA-Ks. HA-Ks exhibited higher viscosity due to greater weight-average molecular weight compared with HA-Mc. HA-Ks had significantly greater submucosal elevation height (SEH) than HA-Mc; the SEH of HA-Ks-80% (80% dilution of HA-Ks) was the same as that of HA-Mc. The ESD procedure time was significantly shorter with HA-Ks than with HA-Mc (15.2 ± 4.1 vs. 19.5 ± 5.9; P = 0.049). The total injection volume for HA-Ks was significantly lower than that for HA-Mc (10.8 ± 3.6 vs. 14.4 ± 4.6; P = 0.045). However, no significant difference in these items was observed between HA-Mc and HA-Ks-80%. HA-Mc and HA-Ks were considered to be almost the same. Nonetheless, HA-Ks exhibited higher viscosity and SIM performance than HA-Mc. HA-Ks-80% had almost the same performance as HA-Mc. Thus, understanding SIM performance and characteristics requires a focus on the viscosity of SIMs.

Viscosity: An important factor in predicting the performance of submucosal injection materials

Viscous submucosal injection materials (SIMs) that are clinically used in endoscopic treatments for early gastrointestinal cancer and polyps contribute to the treatment effects. However, the relationship between SIM characteristics [such as injection pressure (IP) and submucosal elevation height (SEH)] and viscosity has not been evaluated. The aim of this study was to analyze this relationship and elucidate whether it is possible to predict the SIM characteristics by viscosity measurements. Viscosity, IP, and SEH of conventional and developing SIMs were measured, and the correlation between these values was evaluated. A newly developed measurement model accurately measured IP. The magnitude of IP increased as the endoscopic injection needle gauge, injection speed, and concentration of SIM were increased. The strongest correlations were observed between viscosity at a shear rate of 103 s−1 and IP (correlation coefficient > 0.9, p < .01) and between viscosity at a shear rate of 100 s−1 and the SEH (correlation coefficient > 0.9, p < .01). This study defined the viscosities that represent the SIM characteristics. These findings will contribute to the design and accelerate the development of suitable high-performance SIMs by eliminating complex characterization methods.

An innovative next-generation endoscopic submucosal injection material with a 2-step injection system (with video)

Next-generation submucosal injection materials (SIMs) with higher performance and flexibility than the current SIMs (eg, 0.4% sodium hyaluronate solution [HA]) are expected to improve the outcomes of endoscopic submucosal dissection (ESD) but are difficult to develop. We developed a next-generation SIM by devising a 2-solution-type SIM comprising 2.0% calcium chloride solution (Ca) and 0.4% sodium alginate solution (SA) and evaluated its performance. Viscoelasticity, submucosal elevation height, and injection pressure of HA, SA, and the next-generation SIM were measured. Outcomes of ESDs on pseudo-lesions in exvivo porcine stomach/colon models were compared. The dramatic increase in SA viscoelasticity with the addition of Ca facilitated the formation of highly viscous submucosal cushions that can be controlled by endoscopists. The submucosal elevation height of the next-generation SIM was significantly higher than that of HA or SA with the same injection pressure. The ESD procedure time using the next-generation SIM was significantly shorter than that using HA or SA (14.2 ± 6.1 vs 29.2 ± 9.1 minutes, P= .0004, or 14.2 ± 6.1 vs 29.1 ± 5.9 minutes, P<.0001). Furthermore, the total injection volume for the next-generation SIM was considerably lower than that for HA or SA (7.0 ± 0.9 vs 17.2 ± 3.4 mL, P<.0001, or 7.0 ± 0.9 vs 16.2 ± 2.9 mL, P<.0001). We developed an ideal next-generation SIM that achieved high performance and high flexibility in exvivo models. Our findings warrant further investigations in a patient population.

Adhesive Submucosal Injection Material Based on the Nonanal Group-Modified Poly(vinyl alcohol)/α-Cyclodextrin Inclusion Complex for Endoscopic Submucosal Dissection.

Complete resection of early-stage cancer and subsequent wound care of the resection site are both important factors for successful endoscopic submucosal dissection (ESD). Although many submucosal injection materials (SIMs) have been developed to lift up lesions and completely remove cancers, a lack of materials with multiple functions, such as stable submucosal cushion formation, emergency perforation closure, and blood coagulation and wound sealing abilities, still exists. In this study, an adhesive submucosal injection material based on nonanal group-modified poly(vinyl alcohol) (C9-PVA) and α-cyclodextrin (α-CD) was developed to solve clinical problems associated with ESD. Focusing on the inclusion ability of α-CD for alkyl groups, a water-soluble α-CD/C9-PVA inclusion complex (IC) was prepared using water-insoluble C9-PVA in aqueous solutions. The IC of 2.5 mol % nonanal group-modified PVA (2.5C9-PVA), with 53 mM α-CD, showed good gel-sol reversibility and high injectability. Additionally, the α-CD/2.5C9-PVA IC performed well at submucosal cushion formation, with the increased height reaching 5.90 ± 0.38 mm. The complex also adhered well to the submucosa, successfully sealing wounds for over 7 days even in an aqueous environment. Furthermore, following incubation in physiological saline (1.80 ± 0.37 kPa), the burst strength of the α-CD/2.5C9-PVA IC was 1.5-fold higher compared with that of the commercial fibrin sealant, illustrating the possibility of emergency perforation closure. Finally, the complex promoted blood coagulation when mixed with fresh porcine whole blood. These results indicate that the multifunctional α-CD/2.5C9-PVA IC could be an ideal material for ESD.

Cellulose nanofiber dispersion as a new submucosal injection material for endoscopic treatment: preliminary experimental study.

Background and aims Although various solutions have been tested for submucosal injections during endoscopic treatment, the ideal solution has not been established. We investigated the suitability of a cellulose nanofiber (CNF) dispersion with high viscosity and thixotropy as a potential submucosal injection material for endoscopic treatment. Methods We evaluated the catheter injectability and mucosa-elevating capacity of CNF dispersion compared with sodium hyaluronate (SH) solution, which has been reported to be a promising submucosal injection solution. The catheter injectability of CNF dispersion was examined under conditions equivalent to those used clinically in endoscopic treatment. The mucosa-elevating capacity of CNF dispersion was examined in porcine stomachs. Results There was no significant difference between the catheter injectability of 0.4 % CNF dispersion and 0.4 % SH solutions; however, 0.4 % CNF dispersion maintained significantly higher and longer elevation of the submucosal layer than 0.4 % SH solution. A clear separation of the mucosal layer from the underlying muscle layer was achieved by injecting 0.4 % CNF dispersion. Conclusion This preliminary study suggests that CNF dispersion could be an ideal submucosal injection material for endoscopic treatment because of its unique high thixotropy index.

Development of Sodium Polyacrylate-Based High-Performance Submucosal Injection Material with Pseudoplastic Fluid Characteristics.

The development of high-performance submucosal injection materials (SIMs) has significantly contributed to the advancement of rapid and safe endoscopic submucosal dissection (ESD). A previous study authored by us described that pseudoplastic fluid was more suitable for high-performance SIMs than Newtonian fluid. Herein, a novel high-performance SIM is developed, which is primarily composed of sodium polyacrylate (SPA) and exhibits pseudoplastic fluid characteristics. As a representative of current high-performance SIMs with Newtonian fluid characteristics, 0.4% sodium hyaluronate (HA) was selected as the target for comparison. Further, viscoelasticity, submucosal elevation height (SEH), and injection pressure (IP) of HA and SPA were evaluated. The results obtained by ESD were compared using HA or SPA in an ex vivo model. According to the measured viscoelasticity, the concentration of SPA was adjusted to 0.07%; this was aimed at obtaining the IP of SPA, which is equal to that of 0.4% HA. Moreover, no significant difference was observed between the IP values (31.6 ± 1.7 vs 31.4 ± 3.1 psi). SEHs of 0.07% SPA were higher than those of 0.4% HA at all postinjection times (P < 0.001). The duration of the ESD procedure using 0.07% SPA was significantly shorter than that obtained using 0.4% HA (16.6 ± 3.7 vs 22.2 ± 2.9 min, P = 0.0276); further, the total volume of the injected 0.07% SPA was significantly less than that of 0.4% HA (9.0 ± 3.1 vs 15.7 ± 3.9 mL, P = 0.0165). Based on rheological analysis, a high-performance SIM (0.07% SPA) with pseudoplastic fluid characteristics was theoretically developed. It was observed that the SIM performance of 0.07% SPA was higher than that of 0.4% HA.

EndoClot®SIS Polysaccharide Injection as a Submucosal Fluid Cushion for Endoscopic Mucosal Therapies: Results of Ex Vivo and In Vivo Studies.

There are many studies on submucosal injection materials, but their clinical use is restricted for various reasons. The objective of this study was to compare the feasibility and safety of injected EndoClot®SIS polysaccharide as a submucosal injection material (SFC) in ESD in the pig stomach to that of injected sigMAVisc™ or Eleview™. Four pig stomachs were used for the ex vivo study. Eighteen pigs were used for the in vivo study. In the ex vivo study, four injections were made in the gastric submucosa to induce submucosal uplift and extend its duration. Tissue change was observed. The in vivo study was performed in 2 steps. First, 3 injections were made in the esophageal mucosa to induce submucosal uplift and extend its duration. Histological change was observed. Second, ESD was performed in the stomach by injecting EndoClot®SIS polysaccharide, sigMAVisc™, or Eleview™ (each, n = 6) as an SFC. The effects of these agents on wound healing were examined. We evaluated the efficacy and safety of endoscopic surgery after EndoClot®SIS polysaccharide injection. EndoClot®SIS polysaccharide produced a longer-lasting elevation with clearer margins than was achieved by sigMAVisc™, Eleview™, or 0.9% NaCl and thereby enabled precise ESD without complications, such as bleeding and perforation. No obvious histopathological damage was observed at the injection site on endoscopy and histology. Submucosally injected EndoClot®SIS polysaccharide increased the effective separation of the mucosa and submucosa and reduced surgical complications. Hence, EndoClot®SIS polysaccharide injection is a safe and effective submucosal injection material.

Potential of temperature-response collagen-genipin sols as a novel submucosal injection material for endoscopic resection.

Background and study aims We developed a novel submucosal (SM) injection material that contained pepsin-solubilized collagen (PSC), genipin (Ge) and phosphate buffer (PB). The aim of this study was to validate safety and usability of it for endoscopic resection (ER). Materials and methods In preliminary studies, 1) appropriate warming time and concentration of Ge, and concentration of NaCl in PB, 2) storage modulus of PSC, Ge, and PB mixture (PSC/Ge), and PSC as a mechanical property, 3) histological finding after injection, and histological toxicity of PSC/Ge was evaluated. We injected PSC/Ge, PSC, sodium hyaluronate (SH), dextrose (DW), and normal saline (NS) into SM of resected porcine stomach. We compared mean height of mucosal elevation after immediate injection (MH) and mean retaining rate at 60 minutes (MR) as ex vivo study. Results Optimal condition of PSC/Ge was Ge 5.5 mMol with 24 hours worming time and NaCl 280 mMol. PSC/Ge had better mechanical property than PSC. It was efficiently integrated and confined to the SM with acceptable toxicity. MH of PSC/Ge (5.1 ± 0.74 mm) and PSC (4.8 ± 0.84 mm) were significantly higher than NS (3.2 ± 0.84 mm). MR of PSC/Ge (100 ± 0.0%) was significantly higher than NS (61.7 ± 11.2%), DW (58.3 ± 11.8%) and SH (61.8 ± 8.6%). Conclusion PSC/Ge and PSC has potential to be safe and usable for ER. PSC/Ge was better than PSC because of better mechanical property than PSC.