Open AccessEnhanced vascularization and de novo tissue formation in hydrogels made of engineered RGD-tagged spider silk proteins in the arteriovenous loop model
Author(s) -
Dominik Steiner,
Sophie Winkler,
Stefanie Heltmann-Meyer,
Vanessa T. Trossmann,
Tobias Fey,
Thomas Scheibel,
Raymund E. Horch,
Andreas Arkudas
Publication year - 2021
Publication title -
biofabrication
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.328
H-Index - 80
eISSN - 1758-5090
pISSN - 1758-5082
DOI - 10.1088/1758-5090/ac0d9b
Subject(s) - self healing hydrogels , tissue engineering , biomedical engineering , scaffold , biocompatibility , materials science , silk , fibrin , spider silk , angiogenesis , biology , medicine , cancer research , immunology , polymer chemistry , metallurgy , composite material
Due to its low immunogenic potential and the possibility to fine-tune their properties, materials made of recombinant engineered spider silks are promising candidates for tissue engineering applications. However, vascularization of silk-based scaffolds is one critical step for the generation of bioartificial tissues and consequently for clinical application. To circumvent insufficient vascularization, the surgically induced angiogenesis by means of arteriovenous loops (AVL) represents a highly effective methodology. Here, previously established hydrogels consisting of nano-fibrillary recombinant eADF4(C16) were transferred into Teflon isolation chambers and vascularized in the rat AVL model over 4 weeks. To improve vascularization, also RGD-tagged eADF4(C16) hydrogels were implanted in the AVL model over 2 and 4 weeks. Thereafter, the specimen were explanted and analyzed using histology and microcomputed tomography. We were able to confirm biocompatibility and tissue formation over time. Functionalizing eADF4(C16) with RGD-motifs improved hydrogel stability and enhanced vascularization even outperforming other hydrogels, such as fibrin. This study demonstrates that the scaffold ultrastructure as well as biofunctionalization with RGD-motifs are powerful tools to optimize silk-based biomaterials for tissue engineering applications.