Ingestible capsules carrying 3D printed springs: a possible future prospective for SBS treatment?

Abstract

Background Short Bowel Syndrome (SBS) is a malabsorption syndrome characterised by a severe reduction of the absorbent surface of the intestinal mucosa. Treatment of this condition needs multi-professional teams and different therapies, which are not always enough to ensure enteral autonomy. New techniques are being explored, particularly distraction enterogenesis, which can allow the lengthening of the residual intestines of these patients. This study aims to demonstrate the possibility of using biodegradable materials to design ingestible capsules which carry 3D-printed springs capable of reaching the patient’s intestine. These devices could be used as a slightly invasive distraction enterogenesis technique, stimulating cell proliferation and intestinal elongation without surgery. Materials and methods Capsules were realised with gelatin from pigskin type A from Sigma-Aldrich mixed with regenerated silk fibroin (RS) obtained by reverse engineering on Bombyx Mori cocoons. Springs are composed of a structure of regenerated silk (RS) modified with graphene nanoplatelets (GNP) externally covered with a biodegradable polyhydroxybutyrate-valerate (PHBV) shell. Springs were realised with 3D printing, through which, with an extruder, PHBV and RS compounds are deposited simultaneously in a 3D structure. The springs’ capsules were then analysed with solvents simulating the gastric and intestinal environment to verify their resistance to degradation. PBS (Phosphate Buffered Saline), composed of calcium chloride and magnesium chloride (CaCl 2 + MgCl 2 ), with a pH value of 7.4, was used as a degradative agent; for the gastric tract, we chose the acetic acid, CH 3 COOH, at 12% with a pH value of 2.3. Results While the gelatin-only capsules showed poor resistance to degradation in PBS, the new compound based on gelatin and regenerated silk showed excellent resistance in gastric and intestinal environments, allowing the pills to reach the intestine without dissolving. In addition, the results show variability in the release times of the springs as a function of the pH values and the elastic constants of the springs used: the latter determined that in acetic acid, the release time is increased at an increase of the elastic constant. In contrast, in PBS, an opposite trend was observed. Conclusions Our results confirm the possibility of using gelatin, silk fibroin and PHBV to design devices capable of transporting implantable endoluminal 3D structures, drugs, or growth factors, laying the foundations for a new approach to distraction enterogenesis in SBS patients.