In Vivo Retention Quantification of Supramolecular Hydrogels Engineered for Cardiac Delivery

Maaike J.G. Schotman, Marijn M.C. Peters, Gerard C. Krijger, Iris van Adrichem, Remmert de Roos, John L.M. Bemelmans, Maarten J. Pouderoijen, Martin G.T.A. Rutten, Klaus Neef, Steven A.J. Chamuleau, Patricia Y.W. Dankers (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

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-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.

Original languageEnglish
Article number2001987
Number of pages11
JournalAdvanced Healthcare Materials
VolumeXX
Issue numberXX
Early online date15 Feb 2021
DOIs
Publication statusE-pub ahead of print - 15 Feb 2021

Keywords

  • cardiac injection
  • imaging
  • quantification retention
  • radioactive labeling
  • supramolecular hydrogels

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