Functional Imaging for Regenerative Medicine: Tracking Vascularization of Intestinal Scaffolds

Abstract

Traditional approaches to tissue-engineered small intestine (TESI) require implanting a construct in the omentum of the abdominal cavity to allow for vascularization of the construct and tissue maturation. A second operation is then needed to implant the construct in continuity with the intestine. The timing of the second operation has historically been chosen based on predetermined biological endpoints. Currently, no well-validated method has been used to noninvasively monitor for vascular maturity which would better inform when the second operation should be performed. We hypothesized that photoacoustic imaging (PAI) could serve as a tool to noninvasively monitor regional and temporal changes in vascular maturity in scaffolds implanted in the omentum. For this pilot study, tubular scaffolds used for TESI were fabricated with electrospinning and implanted in the omentum of Sprague–Dawley rats for 1 and 2 months. Scaffolds were imaged with PAI and tissue oxygenation and hemoglobin concentration were quantified. PAI was then correlated with gross observations of vascularization at each time point. PAI was able to determine regional and temporal changes in tissue oxygenation and hemoglobin concentration. Specifically, the oxygenation and hemoglobin concentration of the top wall of the construct showed better vascular maturity compared with the bottom wall. In addition, vascular maturity seemed to improve in the top wall from 1 to 2 months. The bottom wall was not well covered by the omentum and thus did not vascularize as well as the top wall. The PAI findings were confirmed on gross examination of the scaffolds and upon quantification of the histological analysis of endothelial cell density. Thus, PAI may serve as a critical tool for monitoring vascular maturity in TE, specifically within the abdomen. This will be a critical tool in the preclinical development and clinical translation of TESI.

Impact Statement

Imaging methods to track functional changes in tissue-engineered constructs are need. These critical tools will be essential for tissue-engineered small intestine (TESI) development and clinical translation. In particular, understanding when a TESI construct has achieved vascular maturity is required prior to placing the TESI in connection with native intestine. In this proof-of-concept study, we have shown that photoacoustic imaging can be used to noninvasively track construct vascular maturity and that the imaging correlates with end-point histology. In addition to TESI, this tool is broadly applicable to all tissue-engineered constructs.