Development of a reproducible automated realistic in vitro gastric model

Abstract

Despite the development of several anatomical accurate digestion models with dynamic behaviour, few of them can be easily reproduced in the laboratory (i.e., both gastric compartment -GC and peristaltic bands - PB). This way, the present study proposes the development of a reproducible fully automated in vitro gastric model through the application of 3D printing technology to produce both the GC and the peristaltic contractions mechanism using silicone. The moulds of both the GC and PB (which design is based on the pneumatic soft robotic actuator developed by the Whitesides Research Group at Harvard), were developed using computer aid design software and 3D printed using fused deposition modelling. In order to optimize the design of the PB, an experimental design (i.e., Plackett-Burman followed by a central composite rotational design - CCRD) was applied using the PB rotation angle (i.e., obtained in silico) as an optimization parameter. The PB rotation angle was determined using a finite element analysis to simulate it inflation, at a fixed pressure for all the PB parameters of the experimental design. Furthermore, to characterize the peristalsis of the in vitro gastric model, the dissolution profile of a 0.006% riboflavin solution was assessed through fluorimetry and compared with the INFOGEST in vitro static model and TIM-1 based in vitro dynamic model. Plackett-Burman experimental design show that the PBs chamber contact thickness (CCT) and the number of chambers (NC) significantly impact the rotation angle of the PB. These parameters were subsequently used in the CCRD which indicated that a design with 2.5 mm of CCT and 15 NC would have a rotation angle of 83.3º. Moreover, the fluorimetry results showed a more accurate riboflavin dissolution profile when compared to other in vitro digestion models due to more realistic peristaltic movements frequency.