In Vivo Retention Quantification of Supramolecular Hydrogels Engineered for Cardiac Delivery

Recent advances in the field of cardiac regeneration show great potential in the use of injectable hydrogels to reduce immediate flush‐out of injected factors, thereby increasing the effectiveness of the encapsulated drugs. To establish a relation between cardiac function and retention of the drug‐encapsulating hydrogel, a quantitative in vivo imaging method is required. Here, the supramolecular ureido‐pyrimidinone modified poly(ethylene glycol) (UPy‐PEG) material is developed into a bioactive hydrogel for radioactive imaging in a large animal model. A radioactive label is synthesized, being a ureido‐pyrimidinone moiety functionalized with a chelator (UPy‐DOTA) complexed with the radioactive isotope indium‐111 (UPy‐DOTA‐111In) that is mixed with the hydrogel. Additionally, bioactive and adhesive properties of the UPy‐PEG hydrogel are increased by supramolecular introduction of a UPy‐functionalized recombinant collagen type 1‐based material (UPy‐PEG‐RCPhC1). This method enables in vivo tracking of the nonbioactive and bioactive supramolecular hydrogels and quantification of hydrogel retention in a porcine heart. In a small pilot, cardiac retention values of 8% for UPy‐PEG and 16% for UPy‐PEG‐RCPhC1 hydrogel are observed 4 h postinjection. This work highlights the importance of retention quantification of hydrogels in vivo, where elucidation of hydrogel quantity at the target site is proposed to strongly influence efficacy of the intended therapy. Exact quantification of hydrogel retention and redistribution upon injection is of utmost importance for determining the effectiveness of cardiac therapeutics. Thus, a modular approach to radioactively label a supramolecular hydrogel is developed, which is verified by in vivo scintigraphic imaging in a porcine model after cardiac injection. This method enables drug dose optimization and easy visualization of possible off‐target effects.