3D-Printed Design of Antibiotic-Releasing Esophageal Patches for Animicrobial Activity Prevention.

Abstract

Pharyngo-esophageal defects can cause exposure to various bacterial flora and severe inflammation. We fabricated a biodegradable polycaprolactone (PCL) patch composed of both thin film and 3D printed lattice, and then investigated the efficacy of pharyngo-esophageal reconstruction by using 3D-printed antibiotic-releasing PCL patches that inhibited early inflammation by sustained tetracycline (TCN) release from both thin PCL films and printed rods implanted in esophageal partial defects. PCL was 3D printed in lattice form on a presolution casted PCL thin film at approximately 100 µm resolution. TCN was loaded onto the PCL-printed patches by 3D printing a mixture of TCN and PCL particles melted at 100°C. TCN exhibited sustained release in vitro for over one month. After loading TCN, the patches showed decreased tensile strength and Young s modulus, and less than 20% tetracycline was slowly released from the 2.5% TCN-loaded PCL patches over 150 days. Cytotoxicity tests of extract solutions from patch samples demonstrated excellent in vitro cell compatibility. Antibiotic-releasing PCL patches were then transplanted into partial esophageal defects in rats. Micro-CT analysis revealed no leak of orally injected contrast agent in the entire esophagus. Tissue remodeling was examined through histological responses of M1 and M2 macrophages. In particular, the 1% and 3% TCN patch groups exhibited significant muscle layer regeneration by desmin immunostaining. Further histological and immunofluorescence analyses revealed that the 1% and 3% TCN patch groups exhibited the best esophageal regeneration according to re-epithelialization, neovascularization and elastin texture around the implanted sites. Our antibiotic-releasing patch successfully consolidates the regenerative potential of esophageal muscle and mucosa and the antibacterial activity of TCN for 3D esophageal reconstruction.