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In situ vascularization of injectable fibrin/poly(ethylene glycol) hydrogels by human amniotic fluid‐derived stem cells
Author(s) -
Benavides Omar M.,
Brooks Abigail R.,
Cho Sung Kyung,
Petsche Connell Jennifer,
Ruano Rodrigo,
Jacot Jeffrey G.
Publication year - 2015
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.35402
Subject(s) - self healing hydrogels , fibrin , stem cell , materials science , biomedical engineering , tissue engineering , ethylene glycol , regenerative medicine , biophysics , peg ratio , in vivo , microbiology and biotechnology , chemistry , biology , immunology , medicine , organic chemistry , finance , economics , polymer chemistry
One of the greatest challenges in regenerative medicine is generating clinically relevant engineered tissues with functional blood vessels. Vascularization is a key hurdle faced in designing tissue constructs larger than the in vivo limit of oxygen diffusion. In this study, we utilized fibrin‐based hydrogels to serve as a foundation for vascular formation, poly(ethylene glycol) (PEG) to modify fibrinogen and increase scaffold longevity, and human amniotic fluid‐derived stem cells (AFSC) as a source of vascular cell types (AFSC‐EC). AFSC hold great potential for use in regenerative medicine strategies, especially those involving autologous congenital applications, and we have shown previously that AFSC‐seeded fibrin‐PEG hydrogels have the potential to form three‐dimensional vascular‐like networks in vitro . We hypothesized that subcutaneously injecting these hydrogels in immunodeficient mice would both induce a fibrin‐driven angiogenic host response and promote in situ AFSC‐derived neovascularization. Two weeks postinjection, hydrogels were sectioned, and the following was demonstrated: the average maximum invasion distance of host murine cells into the subcutaneous fibrin/PEG scaffold was 147 ± 90 µm after 1 week and 395 ± 138 µm after 2 weeks; the average number of cell‐lined lumen per square millimeter was significantly higher in hydrogels seeded with stem cells or cocultures containing stem cells (MSC, 36.5 ± 11.4; AFSC, 47.0 ± 18.9; AFSC/AFSC‐EC, 32.8 ± 11.6; and MSC/HUVEC, 43.1 ± 25.1) versus endothelial cell types alone (AFSC‐EC, 9.7 ± 6.1; HUVEC, 14.2 ± 8.8); and a subset of these lumen were characterized by the presence of red blood cells. Select areas of cell‐seeded hydrogels contained CD31 + lumen surrounded by α‐smooth muscle cell support cells, whereas control hydrogels with no cells only showed infiltration of α‐smooth muscle cell–positive host cells. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 2645–2653, 2015.