Distinct Effects of Heparin and Interleukin-4 Functionalization on Macrophage Polarization and In Situ Arterial Tissue Regeneration Using Resorbable Supramolecular Vascular Grafts in Rats

Valentina Bonito, Suzanne E. Koch, Merle M. Krebber, Daniel A. Carvajal-Berrio, Julia Marzi, Renee Duijvelshoff, Emily B. Lurier, Serena Buscone, Sylvia Dekker, Simone M.J. de Jong, Tristan Mes, Koen R.D. Vaessen, Eva M. Brauchle, Anton W. Bosman, Katja Schenke-Layland, Marianne C. Verhaar, Patricia Y.W. Dankers, Anthal I.P.M. Smits (Corresponding author), Carlijn V.C. Bouten (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Two of the greatest challenges for successful application of small-diameter in situ tissue-engineered vascular grafts are 1) preventing thrombus formation and 2) harnessing the inflammatory response to the graft to guide functional tissue regeneration. This study evaluates the in vivo performance of electrospun resorbable elastomeric vascular grafts, dual-functionalized with anti-thrombogenic heparin (hep) and anti-inflammatory interleukin 4 (IL-4) using a supramolecular approach. The regenerative capacity of IL-4/hep, hep-only, and bare grafts is investigated as interposition graft in the rat abdominal aorta, with follow-up at key timepoints in the healing cascade (1, 3, 7 days, and 3 months). Routine analyses are augmented with Raman microspectroscopy, in order to acquire the local molecular fingerprints of the resorbing scaffold and developing tissue. Thrombosis is found not to be a confounding factor in any of the groups. Hep-only-functionalized grafts resulted in adverse tissue remodeling, with cases of local intimal hyperplasia. This is negated with the addition of IL-4, which promoted M2 macrophage polarization and more mature neotissue formation. This study shows that with bioactive functionalization, the early inflammatory response can be modulated and affect the composition of neotissue. Nevertheless, variability between graft outcomes is observed within each group, warranting further evaluation in light of clinical translation.

Original languageEnglish
Article numbere2101103
Number of pages19
JournalAdvanced Healthcare Materials
Volume10
Issue number21
Early online date14 Sep 2021
DOIs
Publication statusPublished - 3 Nov 2021

Keywords

  • biodegradable polymers
  • cardiovascular
  • immunomodulatory biomaterials
  • in situ tissue engineering
  • Raman microspectroscopy
  • supramolecular chemistry
  • tissue-engineered vascular graft (TEVG)

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