Regenerative Response 35 Days After Esophageal Replacement in a Porcine Model; Technical Difficulties and Attempts to Achieve Optimal Tissue Remodeling.

Abstract

<h4>Background</h4>In previous articles, a porcine model for bridging circumferential defects in the intrathoracic esophagus was developed. The aims of this present study were to evaluate the continued healing response after 35 days, avoid stent migration of the esophageal stent, and to investigate whether it would be beneficial to add new extracellular matrix (ECM) to the healing area after 20 days.<h4>Methods</h4>Surgery was performed in twelve piglets, and five different types of stents were used. In two piglets, new ECM was added by endoscope to the area of healing after 20 days. After the animals were euthanized, the esophageal tissue was examined.<h4>Results</h4>Histologic examination after 35 days showed clusters of desmin-positive smooth muscle cells and the sprouting of nerves in the area that was healing. Generally, there were fewer M1 classically activated macrophages in specimens after 35 days when we compared them with the 20-day study. The CD 163 positive macrophages (M2-macrophages) were seen in all specimens. Four piglets did not survive to the end of the study period because of adverse events. Out of the eight piglets that were euthanized after 34 to 35 days, six had stents that had migrated to the stomach. Only in two piglets, who had large rilled stents, did the stents remain in place throughout the study period.<h4>Conclusion</h4>After 35 days, the area of healing did not show more signs of regenerative healing than the 20 days study. A procedure to add a new biomatrix by re-stenting endoscopically after 20 days was performed on two pigs. The procedure was feasible, but due to limb pain in the animals, they had to be euthanized prior to the plan, which prevented the evaluation of the effect on the regenerative response. The regenerative healing that was started needs to be further orchestrated in other ways to produce a more functional outcome with time.