Effect of hydrogel particle mechanical properties on their disintegration behavior using a gastric digestion simulator
Graphical abstract
Introduction
The stomach plays an important role in the digestion of foods in the human digestive tract. The main functions of the stomach include storage, mixing, disintegration, and emptying. Solid food is mechanically broken down by chewing, roughly reducing its size to <5.0 mm (Jalabert-Malbos et al., 2007). The bolus sent from the esophagus to the stomach is then temporarily stored in the stomach for less than 3 h (Camilleri et al., 1985; Gardner et al., 2002). The gastric content comprising food particles, digestive fluids, and digestive enzymes is mixed in the presence of peristaltic motion on the gastric wall. The food particles in the gastric content also disintegrate because of physical movements (antral contraction waves, ACWs) and chemical reactions (digestive enzymes, pH). Because of the gastric disintegration process, most of the digesta with particle diameters less than approximately 2 mm is emptied from the antrum of the stomach (Guo et al., 2014; Kelly, 1980). Investigating the disintegration behavior of solid foods during gastric digestion is a key factor in controlling digestibility and the delivery of the nutrients embedded within foods.
There is an increasing demand for food products whose texture is appropriately designed for elderly, obese, and functional dyspepsia patients. The mechanical properties of solid foods, such as hardness and elasticity, are important parameters for controlling food digestibility in the above-mentioned people. The mechanical properties of hydrogels can be readily varied by adjusting the formulation and/or concentration of the gelling agents (e.g., polysaccharides and proteins). Hydrogels are also commonly used as solid food models in oral food processing research. For example, Ishihara et al. (2014) found that the first size reduction of gellan hydrogels was similar for instrumental compression tests using artificial tongue and in vivo human tests. Kohyama et al. (2016) also identified that the mechanical properties of different types of hydrogels had a strong influence on natural eating behaviors during oral processing in humans. However, the effects of the mechanical properties of hydrogels on their disintegration during gastric digestion remain unclear.
Numerous in vitro and in vivo studies on the gastric digestion of solid foods have been reported over the past two decades (Dupont et al., 2018; Kong & Singh, 2008). The most common in vivo method uses magnetic resonance imaging (MRI), which allows rapid measurements of multiple parameters of gastric function in a single scan (Hoad et al., 2015). This in vivo method is ideal for studying the gastric digestion of solid foods but has drawbacks such as ethical constraints and in some cases being a burden on subjects. Different in vitro digestion models mimicking the gastric digestion process have been proposed as alternatives to in vivo methods. A conventional in vitro digestion model involves shaking tubes or flasks to mix food particles with artificial digestive fluids containing digestive enzyme(s) (McClements & Li, 2010). However, this model does not evaluate the disintegration of food particles appropriately because ACWs are absent.
In vitro dynamic models that can consider ACWs have been developed since the mid-1990s (Dupont et al., 2018; Guerra et al., 2012). The TNO Gastro-Intestinal Model-1 (TIM-1), developed by Minekus et al. (1995), allows contraction movements of the soft, flexible gastric vessel walls driven by periodically controlled hydrostatic pressure outside the walls. The contraction movement enhances the mixing of the gastric content. The Dynamic Gastric Model (DGM) mechanically processes gastric content through the movement of a piston and barrel simulating the rhythmic ACWs of the human stomach (Vardakou et al., 2011). However, these dynamic digestion models can be expensive for daily use in the food industry. Chen et al. (2016) developed a ‘Rope-Driven’ in vitro Human Stomach Model (RD-IV-HSM), with the aim of investigating the effects of gastric morphology on digestion behavior. The RD-IV-HSM modeled the whole gastric morphology using a liquid silicone molding process, and the contraction movements by fastening/relaxing ropes wrapped around the antrum of the modeled stomach. The RD-IV-HSM has reproduced the size distribution of a semi-solid meal during the digestion process; however, it was not effective in breaking down larger food particles into the smaller sizes required for gastric emptying (<~2 mm). An advanced dynamic in vitro human stomach (new DIVHS) system based on the RD-IV-HSM has been developed (Wang et al., 2019). The human gastric simulator (HGS) mimics the ACWs using mechanically operated rollers; however, the ACW-induced motion of the gastric contents cannot be directly observed (Dupont et al., 2018; Kong & Singh, 2008). Recently, in vitro stomach digestion devices based on a similar concept have also been proposed (Barros et al., 2016; Liu et al., 2019).
Our group has developed an in vitro model named the gastric digestion simulator (GDS) that simplifies the major features of the stomach including gastric peristalsis, which mainly progresses in the antrum (distal stomach), and allows operation of quantitatively simulated ACWs and real-time observation of digestion behavior (Kozu et al., 2014). To study physical gastric digestion, Kozu et al. (2015) performed GDS and flask-shaking experiments using agar cubes as a solid food model. It was reported that agar cubes were only broken down in the GDS experiments, which suggests that simulated ACWs contribute to the disintegration of solid foods. However, quantitative evaluations of the physical forces generated by simulated ACWs and the effect of the mechanical properties of solid foods on the disintegration of food particles remain lacking.
In vivo studies focusing on the contraction force and the force experienced by the target solid food particles during gastric digestion have been reported. Vassallo et al. (1992) measured the force generated by ACWs directly using a reaction force catheter. Marciani et al. (2001) observed the degree of gastric disintegration in subjects who ingested agar beads with several different fracture forces using MRI. Kamba et al. (2000) analyzed the absorption of a maker drug in subjects who ingested press-coated Teflon tablets with several different fracture forces. However, the data obtained from these in vivo studies varied widely. We believe that the result reported by Marciani et al. (2001) is the most useful because it provided direct observation of food disintegration in the stomach.
To verify the disintegration performance of the GDS it is necessary to compare the in vitro data obtained from GDS experiments with the above-mentioned in vivo data. Additionally, the quantitative impacts of the mechanical properties of solid foods on the disintegration mechanism remain unclear. The first objective of this study was to validate the GDS device for reproducing human gastric disintegration of solid foods using similar food samples (agar beads with a range of fracture forces 0.53–0.90 N in LBG meals) against the in vivo data. The second objective was to evaluate the effect of the mechanical properties of hydrogel particles on their disintegration behavior caused by the simulated ACWs of the GDS using 5 × 5 × 5 mm hydrogel cubes containing agar or a mixture of agar and native type gellan gum as a model solid food.
Section snippets
Gastric digestion simulator (GDS)
The GDS used for this study (Kozu et al., 2014) was equipped with a vessel that models the antrum and rollers that generate ACWs, which provide mechanical forces on the gastric contents (Fig. 1a). The speed (2.5 mm/s) and generation frequency (1.5 cycle/min) of the ACWs that act on the sidewalls of the GDS vessel were controlled based on literature data for the ACWs of healthy adults (Sun et al., 1995). The standard values of the ACWs obtained from in vivo studies were 1.5–5.0 mm/s and 1–3
Comparison of in vitro and in vivo gastric digestion data for agar beads in LBG meals
In vitro gastric digestion experiments on agar beads in LBG meals were conducted using the GDS. The results obtained in this study were compared with the results of in vivo human gastric digestion reported by Marciani et al. (2001). The spherical agar beads with different agar concentrations in the range 1.5–3.0 wt% prepared in this work had a diameter of approximately 13 mm (Fig. 2), which is similar to those used for the in vivo study (12.7 mm diameter) and their fracture forces ranged from
Conclusions
Based on the comparison of the GDS results and in vivo data (Marciani et al., 2001) using agar beads with different fracture forces in LBG meals, we concluded that the fracture of solid foods caused by the simulated ACWs of the GDS was comparable to that of the human stomach. Our GDS results demonstrated that two fracture mechanisms (brittle fracture and ductile fracture) occurred for hydrogel cubes during gastric digestion. In the case of the low fracture strain hydrogels, the degree of
Declaration of interests
None.
CRediT authorship contribution statement
Zaitian Wang: Methodology, Investigation, Writing - original draft. Hiroyuki Kozu: Conceptualization, Methodology, Writing - review & editing. Kunihiko Uemura: Validation, Resources. Isao Kobayashi: Writing - review & editing, Funding acquisition, Supervision. Sosaku Ichikawa: Funding acquisition, Supervision, Project administration.
Acknowledgments
This work was partially supported by JSPS KAKENHI Grant Number JP17H01957.
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