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Distinct Effects of Heparin and Interleukin‐4 Functionalization on Macrophage Polarization and In Situ Arterial Tissue Regeneration Using Resorbable Supramolecular Vascular Grafts in Rats
Author(s) -
Bonito Valentina,
Koch Suzanne E.,
Krebber Merle M.,
CarvajalBerrio Daniel A.,
Marzi Julia,
Duijvelshoff Renee,
Lurier Emily B.,
Buscone Serena,
Dekker Sylvia,
Jong Simone M. J.,
Mes Tristan,
Vaessen Koen R. D.,
Brauchle Eva M.,
Bosman Anton W.,
SchenkeLayland Katja,
Verhaar Marianne C.,
Dankers Patricia Y. W.,
Smits Anthal I. P. M.,
Bouten Carlijn V. C.
Publication year - 2021
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.202101103
Subject(s) - regeneration (biology) , wound healing , macrophage polarization , thrombus , fibrin , medicine , in vivo , tissue engineering , biomedical engineering , pathology , cancer research , chemistry , macrophage , microbiology and biotechnology , surgery , immunology , in vitro , biology , biochemistry
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.