Image-guided optimization of regenerative graft attachment to the heart.

Abstract

Tissue engineering offers great promise for regenerating damaged organs including the heart. Although direct attachment of grafts at the target site is possible during surgery, minimally invasive delivery and suture-free approaches could reduce patient discomfort and allow repeat administration. However, for the therapy to be effective it is essential that the graft is successfully delivered to the epicardium and retained on target. Here, methacrylated alginate-based shape-memory patches labelled with ¹¹¹InCl₃ and loaded with luciferase expressing stem-cells were either injected towards the epicardium under ultrasound guidance or surgically grafted onto mouse hearts. Patch and cell location were serially tracked using SPECT-CT and bioluminescence imaging. Radiolabelling of shape-memory patches permitted serial tracking of graft location for seven days in-vivo, and revealed that injected patches rarely attached on-target whilst surgically implanted patches rapidly detached from the epicardium. In-vivo imaging was then used to evaluate modifications to biomaterial formulation and patch attachment strategies. This ultimately resulted in effective, suture-free surgical attachment of chitosan-coated patches loaded with luciferase-expressing human embryonic stem cell-derived epicardial cells onto the heart, illustrating a model therapeutic. This translational imaging approach facilitates iterative optimization of a novel biomaterial and could have wide-reaching applications for enhancing a range of regenerative therapies.