A New Ex Vivo Model for the Evaluation of Endoscopic Submucosal Injection Material Performance
October 19th, 2018
We developed a new ex vivo model that applies constant tension to the porcine gastric specimen. This development made it possible to evaluate the performance (the height and duration of the submucosal elevation) of various SIMs accurately. The detailed setup methodology of this new model is explained.
This method can help answer key questions in the biomedical field about medical matter of interest. The main advantage of this technique is that the performance of various submucosal injection matters can be evalauted more accurately than be conventional methods. Begin by cutting six by six centimeter squares from the upper third portion of a porcine stomach and immediately storing the specimens at minus 30 degrees Celsius.
To set up the traction device, connect a stainless steel clip to a key wire and an S-shaped hook, and connect the key wire and hook to a weight. Connect the hook to the other end of the wire and fix pulleys at both ends of the base. Then place a six by six centimeter rubber plate, at the center of the base and place a thawed gastric specimen onto the rubber plate.
Next, pinch the specimen ends with the clip of the traction device, hang the weight through both of the pulleys to apply constant tension to the specimen, and use a digital gauge to measure the pre-injection submucosal elevation height. Then fix the scriber at the height of the mucosal surface, and push preset, to perform a zero point adjustment of the height gauge. To perform a submucosal elevation procedure, use a 2.5 milliliter syringe equipped with a 23 gauge needle, to inject two milliliters of 0.4%sodium hyaluronate, horizontally into the submucosa from the specimen margins.
Then use the digital gauge to measure the submucosal elevation height immediately, and at the indicated time points after the injection. Recording the height displayed on the height gauge, when fixing the scriber to the top of the submucosal elevation. In these representative experiments, the submucosal elevation height was measured after normal saline, or hyaluronate acid injection, using the conventional, and new ex vivo models of analysis.
Although the submucosal elevation height decreased over time after the injection of either solution, in both models, the resulting submucosal elevation heights, after hyaluronate acid injection, were consistently higher than those measured after normal saline injection, regardless of the post-injection time. Notably, the application of a constant tension, resulted in a lower overall variability within the measurements, compared to the no-tension conventional model of measurement. Indeed the submucosal elevation heights obtained at a tension of 3.0 Newtons, were significantly lower than the submucosal elevation heights obtained at 1.5 newtons.
Whereas, no significant differences in submucosal elevation heights were observed using the conventional model, compared to either constant-tension model. After it's development, this technique paves the way for researchers in the field of biomedical matters, to express the use of high-performance submucosal injection materials for endoscopic therapy.
View the full transcript and gain access to thousands of scientific videos
Overview
This study presents a novel ex vivo model for evaluating the performance of submucosal injection materials (SIMs) using porcine gastric specimens. The model allows for the application of constant tension, enabling accurate assessment of the height and duration of submucosal elevation.
Key Study Components
Area of Science
- Biomedical Engineering
- Gastroenterology
- Ex Vivo Models
Background
- Traditional methods for evaluating SIMs may lack accuracy.
- Constant tension application can enhance experimental outcomes.
- Porcine gastric specimens provide a relevant biological model.
- Understanding SIM performance is crucial for medical applications.
Purpose of Study
- To develop a reliable ex vivo model for SIM evaluation.
- To improve the accuracy of performance assessments of various SIMs.
- To provide a detailed methodology for future research.
Methods Used
- Preparation of porcine gastric specimens by cutting and freezing.
- Setup of a traction device using stainless steel clips and weights.
- Application of constant tension to the gastric specimens.
- Measurement of submucosal elevation height and duration.
Main Results
- The new model allows for precise evaluation of SIM performance.
- Consistent application of tension leads to reproducible results.
- Height and duration of submucosal elevation can be accurately measured.
- This method shows advantages over conventional evaluation techniques.
Conclusions
- The developed ex vivo model is a significant advancement in SIM evaluation.
- It provides a framework for future studies in biomedical research.
- Accurate assessment of SIMs can improve clinical outcomes.
Frequently Asked Questions
Executive Industry Relevance
Accurate evaluation of submucosal injection materials (SIMs) is critical for advancing endoscopic therapies in early gastrointestinal cancer. The new ex vivo model enables precise, reproducible measurement of submucosal elevation height under constant tension, reducing variability and improving predictive confidence in SIM performance assessment. This supports target validation and lead identification by identifying critical performance factors that inform SIM development and prioritization.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Scientific Value: Enables interrogation of therapeutic hypotheses by quantifying SIM performance under controlled biomechanical conditions.
- Operational Value: Supports biological de-risking through reproducible submucosal elevation measurements that clarify functional target validation.
- Predictive Value: Identifies critical factors determining SIM performance, enabling data-driven portfolio triage and lead identification.
Screening & Assay Development
- Scientific Value: Prepares validated biological systems for downstream screening by standardizing SIM evaluation under uniform tension conditions.
- Operational Value: Enhances assay reproducibility and quantitative output reliability through constant tension application and digital height gauge measurement.
- Strategic Value: Improves screening readiness and scalability by reducing measurement variability, supporting reliable compound evaluation across SIM types.
Translational & Preclinical Research
- Scientific Value: Provides disease-relevant ex vivo porcine gastric model that aligns with translational biomarker development for endoscopic therapy.
- Operational Value: Ensures continuity from discovery through preclinical validation by delivering consistent, quantifiable SIM performance data.
- Strategic Value: Supports risk-adjusted advancement decisions by enabling accurate comparison of SIMs, reducing late-stage biological risk in therapeutic development.
Pipeline & Workflow Integration
The method integrates into the discovery continuum from Early Discovery to Lead Identification and Preclinical validation by providing quantitative, reproducible SIM performance data that informs go/no-go decisions.
- Discovery Biology: Supports hypothesis testing and pathway clarification by enabling precise measurement of submucosal elevation as a functional readout of SIM efficacy.
- Screening: Delivers assay readiness and quantitative outputs through standardized tension application and digital gauge measurement, ensuring reliable SIM comparison.
- Analytics: Generates measurable, statistically comparable submucosal elevation height and duration data that help teams evaluate SIM performance across conditions.
- Translational Research: Connects to preclinical continuity by using a physiologically relevant porcine gastric model that mimics human submucosal tissue response.
- Enterprise Reuse: Establishes a reusable platform for SIM evaluation that can be applied across multiple projects and material types, reducing redundant model development.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence in SIM performance by reducing variability and enabling accurate detection of performance differences.
- Operational Value: Improves standardization and reproducibility through constant tension application and standardized specimen preparation.
- Strategic Value: Enhances capital efficiency by accelerating SIM development speed through rapid identification of critical performance factors.
- Portfolio Impact: Enables risk-adjusted prioritization and advancement decisions based on quantifiable, reproducible SIM performance metrics.
Implementation Considerations
- Requires expertise in biomedical engineering and ex vivo tissue handling for proper specimen preparation and device setup.
- Depends on instrumentation including stainless steel clips, weights, pulleys, rubber plates, and digital height gauges for tension application and measurement.
- Necessitates cross-team standardization of specimen sourcing, freezing protocols, and tension calibration to ensure reproducibility across laboratories.
- Involves adaptation considerations when applying the model to different tissue types or species beyond porcine gastric specimens.
- Includes practical limitations such as the need for immediate specimen use after thawing and potential tissue degradation over time, which may affect measurement consistency.
