In Vivo Retention Quantification of Supramolecular Hydrogels Engineered for Cardiac Delivery

Abstract

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-111 In) 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.

Follistatin-like 1 promotes proliferation of matured human hypoxic iPSC-cardiomyocytes and is secreted by cardiac fibroblasts

“…Further elucidation of FSTL1 signaling between CMs and cFBs in the healthy and ischemic heart could provide insights into how we can tap into this intercellular communication to support cardiac repair. As we confirm that FSTL1 acts as a secreted, paracrine factor, clinical translation could be accomplished via various delivery routes to ensure effective local concentrations, for example, by applying an epicardial patch, 20 drug-releasing carriers such as injectable gels, 67 or implantable mini-pumps. 68 Large animal models using clinically applicable methodology 69 seem an appropriate means to further investigate the translational potential of FSTL1 for ischemic heart disease.…”

Factors Influencing Retention of Injected Biomaterials to Treat Myocardial Infarction

“…In our group, we showed a ureido-pyrimidinone-based hydrogel that was labeled with a radioactive tracer ( 111 Indium), traceable in vivo. [133] Here, a small pilot showed the redistribution 4 h after injection in a healthy porcine heart, with 8% of the hydrogel being retained at the inject spot, whereas a high content redistributed to the lungs (29% n = 1, 9.5% n = 2) and bladder and urine (16% n = 1, 22% n = 2). When the hydrogel was modified with a recombinant collagen type-1 based material, cardiac retention was around 16% after 4 h, displaying redistribution of the hydrogel mainly to the lungs (13% n = 1, 19% n = 2), as well as the bladder and urine (10% n = 1, 13% n = 2).…”

Synthesis and Processing of Dynamic Covalently Crosslinked Polydextran/Carbon Dot Nanocomposite Hydrogels with Tailorable Microstructures and Properties

“…At low frequency (higher relaxation time), polymer chains start to flow and rearrange, showing liquid-like properties. At high frequency (shorter relaxation time), polymer chains do not have enough time to rearrange and therefore exhibit solid-like properties . Thus, the decreased tan δ of PDA30@CD and PDA50@CD hydrogels with increased frequency indicated that hydrogels had a strong network structure at high frequency .…”